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Taking Heartburn Medicine 3+ Times a Week May Cause Harm

Are you taking medicine three or more times a week for heartburn? If so, read the warning label. Not all heartburn medicines are meant to be used that often, and it could be harming your health. 

Antacid Tablets

Antacids like Tums and Rolaids contain calcium carbonate and magnesium hydroxide to help neutralize the acid in your stomach. They can provide fast, short-term relief and do not have lasting harmful side effects if taken as directed. Follow dosage recommendations though because high levels of calcium carbonate in the body can cause constipation, nausea, mood changes or even heart rate changes. But acid neutralizers are considered safe when taken properly and are often used for calcium supplementation as well as heartburn relief.

H-2 Blockers and Proton Pump Inhibitors (PPIs)

H-2 blockers like Zantac, Tagamet and Pepcid reduce the production of stomach acid. They are effective in treating peptic ulcers and reflux in people who have heartburn a few times per month but are not intended for everyday use. Some research suggests that overuse of H-2 blockers can cause headaches, constipation and nausea, but their long-term use has not been extensively studied.

Proton-pump inhibitors (PPIs) like Prevacid, Prilosec or Nexium are stronger than H-2 blockers and work by blocking acid-producing cells in the lining of the stomach. They provide lasting relief from symptoms of GERD and are available without a prescription.

While PPIs are helpful in managing severe heartburn, they are not recommended for more than a 14-day treatment. Recent studies show that overuse of PPIs can be harmful to your health and should not be used long-term. Side effects of proton pump inhibitors include infections, bone fractures and vitamin and mineral deficiencies. Research has even connecting extended PPI drug use to increased risk of stomach cancer.

Are you trying to manage your heartburn symptoms on your own? It might be time to call a gastroenterologist. Your doctor can diagnose your symptoms and help you begin an effective treatment plan. There also may be some lifestyle changes and diet modifications that can jump-start the healing process, so make an appointment today.

Can you take a PPI forever?

Keith Roach
 |  To Your Health

Dear Dr. Roach: You have written about PPIs such as Prilosec, which I have successfully taken for over 10 years to fight a severe case of GERD with a small hiatal hernia.

However, what is your opinion on my long-term usage (which has been a true lifesaver) and continuing it essentially forever? My gastro specialist seems to be of the “keep taking it” attitude because of its success, but aren’t there potential downsides, specifically to kidney function? Is switching to an h3 blocker like Pepcid or Tagamet any easier on the kidneys?

K.J.

Dear K.J.: All medicines have side effects, and it is worthwhile to periodically examine the risks and benefits of taking a medication long term. You already know the benefit: a large improvement in your quality of life. Balanced against that are several potential risks.

The clearest risk is probably infection. Not being able to make stomach acid puts a person at risk for Clostridium difficile infection (severe diarrhea) and other infections, perhaps including pneumonia. Malabsorption of nutrients, especially magnesium and vitamin B12, is so frequent that testing may be appropriate in people who take PPIs long-term. Calcium may also be affected, potentially increasing risk of osteoporosis. This also deserves screening in the appropriate people at risk.

The association between chronic kidney disease and long-term PPI use is controversial, and is probably small. Still, a periodic check of kidney function is wise. There is weak evidence for a small increase in dementia risk.

With all of these risks, my preference for patients on long-term PPI is to try taking them off the medicine slowly and replace it with an h3 blocker, just as you suggest. It is effective for many, but there are some people who really need a daily PPI in order to not have significant daily symptoms. It is up to the person, but the risk of serious side effects is small enough that the benefit outweighs it for most.

Dear Dr. Roach: After my wife and I receive both shots of the COVID-19 vaccine can we resume our gym classes and return to restaurants? We are both in good health. She is 68 and I am 70.

G.G.

Dear G.G.: Not immediately. The vaccine is given in two doses, three or four weeks apart, and maximum protection isn’t reached for two weeks or so after the second dose. Even then, the protection isn’t perfect: 94% to 95% according to the best studies for the currently available vaccines. Because there remains rampant transmission in all areas of the country, it is safest for you and your wife to continue to socially distance and wear masks. That’s particularly important for people at high risk of complications.

Secondly, although the vaccine is excellent at reducing risk of developing symptomatic COVID-19 infection, it isn’t clear whether it stops asymptomatic infections. It is possible that vaccinated people may be temporarily infectious after being exposed, without ever knowing they might be spreading virus. Until it is known for sure that is not the case, it is safer for others if you and your wife, and all of us who have been vaccinated, continue to wear masks and socially distance.

It is disappointing that we cannot immediately return to our lives before the pandemic began, but the vaccine is only part of the solution. We cannot let up on the rest of the behaviors we need to continue to stop the pandemic.

Readers may email questions to [email protected]

Can long-term use of acid reflux drugs cause cancer?

Proton pump inhibitors (PPIs) are the most prescribed drugs in the United States. Americans spend more than $10 billion a year on these drugs, which include omeprazole, lansoprazole, rabeprazole and esomeprazole, designed to treat acid reflux and helicobacter pylori (H. pylori) infections. Now, after the drugs have been on the market for 25 years—the last 16 years of which they have been available without a prescription—some doctors and researchers are questioning whether protracted use of PPIs comes with long-term side effects, including the possibility of an increased cancer risk.

“In the short term, they are likely to be very safe,” says Anthony Perre, MD, Chief of the Division of Outpatient Medicine at Cancer Treatment Centers of America® (CTCA). “But I think it’s really important to critically evaluate the need for a person to remain on a proton pump inhibitor long term.”

How do proton pump inhibitors work?

The stomach digests food with the aid of gastric acid, a mix of hydrochloric acid, sodium chloride and potassium chloride. This highly corrosive soup is produced when gastric cells (G-cells) in the stomach secrete the hormone gastrin, which signals parietal cells in the stomach to start pumping acid. PPIs shut down the proton pumps in the parietal cells, cutting off the production of acid. “If you are blocking acid production by using a proton pump inhibitor, the body says, ‘I don’t have enough acid. Make more.’ So, the way the body reacts is for G-cells to produce more gastrin,” Dr. Perre says. Too much gastrin may stimulate the growth of gastrointestinal tumors. Ironically, proton pump inhibitors often are prescribed to treat acid reflux, also called gastroesophageal reflex disease (GERD), or H. pylori infections, conditions that may increase the risk of stomach and esophageal cancers. “It is a double-edged sword,” he says.

Two studies conducted in 2017 and 2018 concluded that long-term use of PPIs may increase the risk of stomach cancer, also called gastric cancer. Researchers at the University of Hong Kong studied more than 60,000 patients who took PPIs to treat H. pylori. These bacteria, which live in the digestive system, can cause ulcers and increase the risk of stomach or esophageal cancer. The Hong Kong study concluded that long-term PPI use more than doubled the risk of stomach cancer. A Swedish study of patients on PPI therapy drew similar conclusions. But other research has contradicted those findings, Dr. Perre says. The Canadian Association of Gastroenterology, for instance, said the Hong Kong study conclusions were “unjustified. ” “There is some discussion and controversy over whether they do or do not increase cancer risk,” Dr. Perre says.

What should PPI patients do?

So, should a patient who is on PPIs stop taking them? The answer is not always simple. Dr. Perre suggests patients who have been on PPIs consult their doctor about their prescription. But, he advises, patients should not stop taking PPIs cold turkey. “Often, people have rebound symptoms after cutting them off abruptly,” he says. Patients with GERD may be able to remain off PPIs if they modify their diet and lifestyle by, for example, not smoking, reducing alcohol and caffeine, avoiding spicy foods and not eating late at night. “It’s clear that lifestyle and diet modification should be the base of the pyramid with any treatment of a patient with acid reflux,” Dr. Perre says. “But in some people where that doesn’t work, they may need to be on proton pump inhibitor therapy long term.” In the end, though, whether to continue taking the drugs should be a decision made in consultation with your doctor. Patients should talk to their doctors about long-term PPI use and follow their recommendations on whether to stay on the drugs or use another intervention.

Learn more about gastroenterology treatments for cancer.

Heartburn Medicine: Safety and Risk Factors of Common Heartburn Drugs

Millions of people worldwide have taken proton pump inhibitors (PPIs) since 1989 to manage gastroesophageal reflux disease (GERD) and other reflux disorders. These drugs have been heavily advertised, and many people today routinely take the “little purple pill” and similar medicines for months or even years at a time without getting a prescription, according to the U.S. Food and Drug Administration (FDA).

While most patients don’t experience safety issues, studies over the years have raised questions about a number of serious and potentially life-threatening side effects. Among other things, these pills have been tied to an increased risk of premature death, heart disease, certain cancers, dementia, lung disorders, fractures, kidney damage, pneumonia, and bacterial infections.

Here’s what you need to know to decide if these drugs are right for you, and whether you need to see a doctor before you try over-the-counter PPIs.

What Is Heartburn and How Can PPIs Help?

Heartburn happens to lots of us when we have an especially spicy, fatty, or heavy meal. It develops when stomach acid flows up into the esophagus, or food pipe, causing a burning sensation in the chest, often accompanied by a bitter or sour taste in the mouth and throat. Symptoms are especially common among the elderly, pregnant women, smokers, and people who are overweight or obese.

More than 60 million Americans experience heartburn at least once a month, and more than 15 million people suffer daily symptoms, according to the American College of Gastroenterology.

Sometimes heartburn eases with lifestyle changes, like eating smaller meals and eating more slowly. Avoiding tobacco, alcohol, and caffeine can also help.

Over-the-counter antacids, like Alka-Seltzer, Mylanta, and Tums, can help ease occasional pain and discomfort caused by heartburn or acid reflux. But these drugs don’t actually stop acid production.

That’s where PPIs come in. Sold under brand names like Prilosec (omeprazole) and Nexium (esomeprazole), PPIs work by curbing production of stomach acid. Doctors prescribe these drugs to treat GERD, a condition that develops when stomach acid backs up into the esophagus. PPIs also treat Helicobacter pylori, a bacteria that can cause ulcers in the stomach and small intestine. And, the drugs can also halt the production of stomach acid that causes ulcers with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), like aspirin and ibuprofen (Advil or Motrin).

When doctors prescribe PPIs, benefits like reducing hospitalizations for GERD generally outweigh the risk of rare side effects associated with the drugs, says Joel Rubenstein, MD, an associate professor of gastroenterology at the University of Michigan Medical School in Ann Arbor. But the picture is different for many people who buy PPIs without ever seeing a doctor, he adds.

`Zero Benefit’

“Many millions of patients with symptoms thought to be due to GERD are taking a PPI,” but don’t actually have GERD or need these drugs, Dr. Rubenstein says. “In these patients, the tiny risks of PPI and substantial financial cost are not worth the zero benefit.”

People who take over-the-counter PPIs shouldn’t stay on these drugs for more than two weeks or turn to these drugs more than once every four months without seeing a doctor, according to warning labels on the medicines.

“The side effects are rare only if the course is a short-term one; less than two or a maximum of three weeks,” says Ruben Abagyan, PhD, a professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California in San Diego.

“The side effects look almost inevitable if the drugs are taken for a long period of time,” Dr. Abagyan says. And there’s research to support that.

First off, there’s the potential for PPIs to lead to an early grave. One observational study published in July 2017 in the journal BMJ followed almost 350,000 U.S. veterans for a median of 5.7 years and found patients who got new PPI prescriptions were 23 percent more likely to die during follow-up than people who didn’t take acid-suppression drugs.

The same research team published a longer study in May 2019 in BMJ that followed almost 215,000 veterans. This time, they found the drugs associated with a 10-year mortality risk of 45 excess deaths for every 1,000 patients.

“The absolute risk is small, but given the millions of people on PPIs, the overall population level risk is substantial,” says senior author of both studies Ziyad Al-Aly, MD, director of the clinical epidemiology center and chief of research and education service at Veterans Affairs St. Louis Health Care System in Missouri.

Generally, the risk of side effects is higher in people who don’t need PPIs but take them anyway, Dr. Al-Aly says. He, too, cautioned against using the OTC drugs for more than two weeks without seeing a doctor.

Most of the studies that have found safety issues with PPIs weren’t clinical trials designed to prove whether or how these drugs might directly cause certain side effects. Instead, they were observational studies that simply looked at data on large groups of people to compare health outcomes for patients who took PPIs and patients who didn’t.

Absolute Risk for Serious Side Effects Is Low

For many other serious side effects associated with PPIs, the absolute risk is low and the evidence isn’t definitive, says Dhyanesh Patel, MD, an assistant professor of medicine at the Center for Swallowing and Esophageal Disorders at Vanderbilt University Medical Center in Nashville, Tennessee.

One study examining the link between PPIs and kidney disease found the drugs associated with up to a 0.3 percent greater risk of kidney disease per patient for each year on the drugs.

Another study found the medicines associated with up to a 1.5 percent greater risk of dementia per elderly patient per year.

And, each year on PPIs was associated with up to a 0.5 percent higher risk of hip fractures for older adults taking the drugs in a different observational study.

These links — and connections to several other side effects — aren’t strong enough at this point for patients to steer clear of PPIs just because they have other risk factors, several doctors said.

Elderly patients, for example, might be more prone to side effects associated with PPIs because of multiple chronic health problems that are unrelated to the PPIs and might be tied to their use of other medication, Dr. Patel says.

“PPI therapy might be entirely appropriate, but yet may be blamed for any subsequent adverse event,” Patel says.

Infections Are Clearest Risk

The clearest exception may be infections, which have been consistently linked to PPIs in several large, observational studies over the years.

One three-year study, published in May 2019 in the journal Gastroenterology, randomly assigned more than 17,000 patients to take a PPI or placebo in combination with blood-thinners, and found PPI users were 33 percent more likely to develop enteric infections. These infections develop in the small intestine and are caused by a type of bacteria known as campylobacter. Enteric infections are a leading cause of diarrhea.

More than 900 people would need to take PPIs for over a year for one patient to develop an enteric infection that wouldn’t have otherwise occurred, says Paul Moayyedi, PhD, lead author of the study and assistant dean of research at McMaster University in Hamilton, Ontario, Canada.

Patients on PPIs in this study were also more than twice as likely to develop Clostridium difficile infections, but there were only 13 cases and this made it impossible to rule out the possibility that the connection might be due to chance.

So-called C. diff infections can cause symptoms ranging from diarrhea to life-threatening inflammation in the colon.

Of all the potential safety concerns with PPIs, the risk of infections is one that doctors most consistently say changes how they prescribe the drugs.

“I try to get patients off PPIs or minimize the dose if they have had C. diff,” says Rubenstein. “And I recommend that patients who have household contacts with enteric infections hold the PPI for a week to 10 days to reduce the risk of contracting the infection.”

Study Leaves More Questions Than Answers

Beyond the elevated infection risk, this study didn’t find a connection between PPIs and several other safety issues it examined that have been identified by earlier research. PPIs didn’t appear to cause fractures, kidney disease, dementia, cancer, heart disease, chronic obstructive pulmonary disease (COPD), hospitalizations, or premature death.

“It is very reassuring that our trial was negative and suggests the risks of PPIs have at the very least been overstated,” Dr. Moayyedi says.

Even though this study was the gold standard for drug safety research — randomly assigning some patients to take a medicine and others to take a placebo — the goal of the study was to test PPI safety only in people with damaged arteries who were prescribed aspirin or the blood-thinner Xarelto (rivaroxaban). It’s possible results would be different in other groups of people.

Some side effects might also surface in a larger, longer study that didn’t appear in this trial. “We still can’t exclude a very small risk of harms,” Moayyedi says.

For now, safety concerns shouldn’t deter doctors from prescribing PPIs to patients who need them, says Vandana Nehra, MD, associate professor of medicine at the Mayo Clinic in Rochester, Minnesota.

That’s because most of the problems identified so far have been found in observational studies that can’t prove PPIs directly caused specific side effects, and because the association usually wasn’t a strong one, Dr. Nehra says.

But patients should still exercise caution and common sense.

Left to their own devices, many patients may take PPIs for conditions that the drugs are designed to treat, then take a higher than recommended dose for longer than they should when the drugs fail to work, Nehra says.

“It’s important to use PPIs under the supervision of a clinician at the lowest effective dose for the shortest period of time,” Nehra advised.

Infants prescribed antacids for reflux have increased risk of bone fractures

SAN FRANCISCO – New research being presented at the 2017 Pediatric Academic Societies
Meeting found infants prescribed antacids to manage acid reflux, or spitting up, under
age 1 had more bone fractures later in childhood.

An abstract of the study, “Early Antacid Exposure Increases Fracture Risk in Young
Children,” will be presented on Sunday, May 7, at the Moscone West Convention Center
in San Francisco.

Acid reflux, also known as gastro-esophageal reflux (GER), is frequently treated with
drugs such as proton pump inhibitors (PPIs) and histamine h3-receptor antagonists
(h3-blockers) that decrease production of stomach acids. These types of medications
have been linked with increased bone fractures in adults, but there has been a lack
of research into whether they might have the same effect in children.

Researchers examined the records of 874,447 healthy children born within the Military
Healthcare System (MHS) from 2001 to 2013 who received care within the system for
at least two years. They found approximately 10% of the children were prescribed antacids
in the first year of life, including h3-blockers such as ranitidine (Zantac) and famotidine
(Pepsid) as well as PPIs such as omeprazole (Prilosec) and pantoprazole (Protonix).
A small percentage was prescribed both.

Children who used PPIs had a 22% increased likelihood of fracture, while children
who used both PPIs and h3-blockers had a 31% increased likelihood of fracture. Use
of h3-blockers was not associated with an immediate increase in factures, the study
found, but there was an increased likelihood of fracture with time.

In addition, the number of bone fractures children experienced increased with the
number of days they took these medications. The younger a child first began using
antacid medications, the higher the fracture risk. Those started on antacid medications
earlier — under 6 months old — had the most increased fracture risk. Children who
started using antacids after age 2 years did not have increased fractures as compared
to children who were not prescribed antacids in the first five years of life.

Use of antacid medications in infants should be weighed carefully against possible
fracture, said U.S. Air Force Capt. Laura Malchodi, M.D., lead author of the study
and a pediatrics resident at Walter Reed National Military Medical Center.

“With many antacids easily available over-the-counter for adults, these medications
may seem benign,” Dr. Malchodi said. “However, our study adds to a growing body of
evidence suggesting antacid medications are not safe for children, especially very
young children, and should only be prescribed to treat confirmed serious cases of
more severe symptomatic gastroesophageal reflux disease (GERD), and for the shortest
length of time needed.

GER is a common condition that affects roughly 40% to 65%t of all infants. It usually
begins at approximately 2 to 3 weeks of life and peaks between 4 to 5 months. In most
babies, GER disappears by about 1 year of age as the upper digestive tract functionally
matures. The American Academy of Pediatrics believes it is important for all pediatric
health care providers to be able to properly identify and treat children with reflux
symptoms, and to distinguish GER from more worrisome disorders so as to avoid unnecessary
treatments.

Dr. Malchodi will present the abstract, “Early Antacid Exposure Increases Fracture
Risk in Young Children,” at 11:45 a.m. It is available at https://registration.pas-meeting.org/2017/reports/rptPAS17_Abstracts.asp.


The Pediatric Academic Societies (PAS) Meeting brings together thousands of individuals
united by a common mission: to improve child health and well-being worldwide. This
international gathering includes pediatric researchers, leaders in academic pediatrics,
experts in child health, and practitioners. The PAS Meeting is produced through a
partnership of four organizations leading the advancement of pediatric research and
child advocacy: Academic Pediatric Association, American Academy of Pediatrics, American
Pediatric Society, and Society for Pediatric Research. For more information, visit
the PAS Meeting online at www.pas-meeting.org, follow us on Twitter @PASMeeting and
#pasm17, or like us on Facebook. For additional AAP News coverage, visit http://www.aappublications.org/collection/pas-meeting-updates

Copyright © 2017 American Academy of Pediatrics

Dangers of Acid Reflux Medications

Is that little purple pill doing more harm than good?

Dr. Kevin E. Ritzenthaler, DC, DCBCN

Burning in the chest and throat. Trouble swallowing. The feeling that food is stuck in your chest or throat. Chest pain (sometimes confused with a heart attack). Chronic cough, sore throat and hoarse voice.  Sound familiar?  If you’re suffering from these common symptoms of heartburn, acid reflux, or GERD, you’re not alone. It’s estimated that upwards of 25 million people suffer from these symptoms on a daily basis.

So, what do you do?

Take the little purple pill, of course.

The fact that you likely know what that little purple pill is without mention of a brand name is a tribute to the power of advertising. But in case you’re drawing a blank, the little purple pill to which I am referring is Nexium.  Or maybe you’re like Larry the Cable Guy, and you reach for Prilosec.

Nexium (esomeprazole), Prilosec (omeprazole), and Prevacid (lansoprazole), are in a class of medications called proton pump inhibitors (PPI).  PPIs reduce the amount of acid in your stomach, which can provide symptom relief for those suffering from acid reflux disease or GERD. There is another class of medications also used to treat these symptoms known as h3-antagonists or h3 blockers. Zantac (ranitidine), Pepcid (famotidine), Tagamet (cimetidine), and Axid (nizatidine) are h3 blockers which also reduce the amount of acid secreted by the stomach.

Okay, let’s think this through.  Stomach acid gets into your esophagus, causing some pretty unpleasant symptoms. So, you take a drug that reduces the amount of acid in your stomach.  Symptoms go away, and life is good. Makes sense.

Or, does it?

We’re missing a step here folks.  We need to ask ourselves WHY the acid is backing up into our esophagus, and the answer is not “because there’s too much acid”.

Stomach Acid Itself is Not The Issue

Question: who suffers more from acid reflux and GERD, teenagers or older adults?  Many studies have shown that GERD increases with age. Studies also show that the production of stomach acid decreases with age.  This is one indication that idea that the amount of stomach acid is not the cause of heartburn, acid reflux, and GERD, because, if it were, the problem would be more prevalent in younger people not older people.

Now let’s look at your anatomy. As food moves from your esophagus to your stomach, it passes through the Lower Esophageal Sphincter (LES). The LES is a valve whose job is to open up to let food pass into the stomach and then remain closed to keep it there. When stomach acid flows backwards (or refluxes) into your esophagus, it is because the valve has not done its job. When the LES works properly, it doesn’t matter how much acid is in your stomach, because the valve will keep it where it belongs.

The question then becomes: what is happening in the stomach that is pushing the acid back up through the LES valve?

One cause is low levels of stomach acid. Yes, you read that correctly.  Having too little acid in the stomach leads to acid reflux.

Stomach acid breaks down food for digestion. In order to do that job, the pH level (or level of acidity) must be within a certain range. The pH levels also signal the opening of the valves at both ends of the stomach.  When pH levels are normal, digestion occurs as it should, and food moves from the esophagus to the stomach to the small intestine.

When acid levels are low (pH levels are high), food does not break down as it should causing overgrowth of bacteria.  When food stays in the stomach for too long, it can ferment and excess gas accumulates.  Now the stomach is filled with gas, but the pH levels are too low to signal the valve to open to the small intestine.  So the body only has one way to relieve the pressure – it opens the LES valve and releases the gas and acid back up into the esophagus.

In addition, a specific bacteria in the stomach, helicobacter pylori (or H. pylori), can attain high levels when stomach acid is too low. This causes inflammation in the lining of the stomach, also known as gastritis.  The symptoms of gastritis are very similar to and often confused with those of acid reflux and GERD. Something else you should know about H. pylori is that it actually reduces the secretion of stomach acids, which sets off a nasty cycle:

Low stomach acid >> heartburn >> taking drugs that decrease acid >> H. pylori infection >> even less stomach acid >> chronic heartburn and GERD

As you can see, taking PPIs or h3 blockers is akin to throwing the baby out with the bathwater:  reducing the much-needed stomach acid (baby) in an attempt to reduce the symptoms of heartburn, acid reflux, and GERD (bath water).

Risks of Acid-Reducing Drugs

In addition to the fact that taking PPIs and h3 blockers do not fix the real cause of acid reflux, they also carry some serious risks, especially when taken beyond packaging instructions.  I’ve already covered the problems caused by acid reduction leading to bacterial overgrowth. Other consequences include reduced nutrient absorption, increased risk of infection, and increased risk of cancer and other diseases.

When you don’t have enough acid, the chemical reactions that are necessary to absorb vitamins, minerals and other nutrients into your bloodstream are impaired. Research confirms that low stomach acid reduces absorption of iron, B12, folic acid, calcium and zinc.

Low iron levels can lead to anemia, resulting in the cells of your body not getting enough oxygen.  Folic acid is essential for cardiovascular health and for preventing some birth defects. Zinc plays a role in many parts of a healthy metabolism including new bone formation, immunity, vision, tissue growth, and the stability of cell membranes. B12 is needed for the normal function of the brain and nervous system. Calcium is important for strong teeth and bones, and some research indicates that long-term use of PPIs is linked to hip fractures.  Calcium also impacts bodily function in many, many other ways.

One of the most important roles of stomach acid is to kill harmful bacteria.  When you reduce the amount of acid in your stomach, you are increasing your risk of infections.  Research has linked acid reducing drugs to increased risk of pneumonia, tuberculosis, typhoid, and disentary. Other studies found evidence of contracting salmonella, campylobacter, chorea, listeria, giardia, and c. difficlie.

Decreased levels of stomach acid can also lead to atrophic gastritis which is associated with an array of serious health concerns including: stomach cancer, allergies, ulcers, asthma, depression, anxiety, auto immune diseases (e.g. RA and Graves disease), Irritable Bowel Syndrome (IBS), Crohn’s disease, ulcerative colitis, and many more.

Read the Labels

It’s estimated that 70 percent of PPI use is outside of FDA guidelines.  According to their dosage instructions, Prilosec OTC can taken for 14 days up to 3 times a year; Nexium and Prevacid can be taken up to 8 weeks; and Pepcid and Zantac are intended to be taken for 14 days.  Yet, it’s not uncommon to talk to people who have been taking these drugs for years, sometimes on the advice of their doctor.

At this point, you might be thinking, “why didn’t anyone tell me these pills are so dangerous?”  In many cases they did. Much of this information is in the fine print that comes along with the medications.   For example, the Nexium Medication Guide lists “serious side effects” including: kidney problems, diarrhea (caused by c.difficlie infection), bone fractures (including hip, wrist, or spine), and lupus. A page or so later it lists “other serious side effects” including vitamin B-12 deficiency and low magnesium levels (whose symptoms include: seizures, dizziness, abnormal or fast heartbeat, jitteriness, tremors, muscle weakness, spasms, cramps or muscle aches). And finally, the “common side effects” include headache, diarrhea, nausea, gas, abdominal pain, constipation, dry mouth, and drowsiness.

If you’re like me, when you read this list of “common side effects” you can also hear it in your head, as your brain recalls the many times you’ve heard that list read during a pharmaceutical TV ad. It seems to me that after hearing these side effects so often, we begin to tune them out. And once we’ve tuned them out, we lose sight of how serious the really are.

But as we tune out or ignore the warnings, studies continue to be published that bring the issues back to the forefront, including those linking extended PPI use to heart disease, kidney failure, and dementia.

Don’t Quit Cold Turkey

If the information presented thus far in this article has you scared (it should) you might be tempted to stop taking PPIs and h3 blockers immediately (you shouldn’t). Quitting PPIs cold turkey can cause a serious rebound effect, making your symptoms worse than before you started taking the medication. In fact, this rebound effect is believed to be responsible for why so many people take these drugs for longer than the recommended term. Rather than quit cold turkey, it is better to enlist the help of a health care professional to wean yourself off of the drugs over time.

Alternative Treatments for Heartburn, Acid Reflux, and GERD

Admittedly, there’s a lot of information in this article. That’s because this is a big, complex issue. It might be hard to digest (excuse the pun) not only because of sheer volume, but also because it’s contradicting what mainstream medicine and media have told you.

If you’re suffering from chronic heartburn, acid reflux, and GERD you need to know that there are other options available to you that don’t involve the use of potentially dangerous drugs. Functional Medicine employs strategies work to fix the root source of the problem and may include eliminating food triggers, increasing the body’s natural production of stomach acid, taking natural supplements, changes to diet and exercise, and other lifestyle modifications.

Remember, drug companies are not interested in cures – it’s bad for their business. If you’re ready to find a healthy way to reduce heartburn, acid reflux, and GERD, I invite you to contact our office at 715-355-4224 to set up a no-cost Functional Medicine consultation.

Treating Heartburn and GERD | Choosing Wisely

Heartburn is a feeling of burning pain in your lower chest, behind the breastbone. It comes from acid backing up from your stomach to your throat. You may have seen ads for heartburn drugs, such as Nexium, Prilosec or Prevacid. These drugs are called PPIs (proton pump inhibitors). They keep the stomach from making too much acid. They have been shown to heal irritation of the tube between the throat and the stomach (the esophagus).

In most cases, you don’t need a PPI for heartburn. You can get relief from a less powerful drug. And when you do need a PPI, you should take the lowest dose for as short a time as possible. Here’s why:

You may not need a PPI?

More than half of the people who take PPIs probably do not need them. Simple heartburn can be treated with antacids or other drugs, plus diet and lifestyle changes.

You may only have heartburn every now and then—such as after a big, spicy meal. This may be uncomfortable, but it is not serious. You can usually get relief from an antacid, like Rolaids or Tums, or an h3 blocker, such as Pepcid AC or Zantac.

PPIs have risks.

If you need a PPI, taking a low dose for less than a year is probably safe. PPIs are expensive and have been linked to higher risk of some
problems. Talk with your doctor before taking them for longer than two weeks. Be sure you have a good reason to take the PPI, and take it
for the shortest time possible.

Some risks of taking a PPI for a year or longer include:

  • Higher risk of certain fractures.
  • Higher risk of kidney disease, or kidney disease that gets worse.
  • A higher risk of heart attack.
  • In people age 75 and older, a higher risk of dementia.
  • Trouble absorbing calcium and vitamin B12.
  • Low levels of magnesium in your blood.
  • Pneumonia.
  • An infection in the intestines called Clostridium difficile.

PPIs can change the way other drugs work.

PPIs interact with some common prescription drugs. For example, some PPIs can reduce the blood-thinning effect of the drug Plavix (generic clopidogrel), according to the US Food and Drug Administration. This can increase the risk of heart attack and even death. If you take Plavix, talk to your doctor about whether you should take a PPI.

PPIs cost more.

Why spend more money on a PPI unless antacids or h3 blockers don’t work? Both the prescription and over-the-counter versions of PPIs are usually more expensive than antacids and h3 blockers. If you are worried about cost, talk to your doctor. He or she can help you find
the least expensive medicine that will work for you.

When should you consider a PPI?

Talk to your doctor if you have symptoms such as trouble swallowing, weight loss, or chest pain. Call the doctor if you don’t get better in about two weeks. The doctor will look for signs of problems such as GERD (gastroesophageal reflux disease).

If you have GERD, you probably need a PPI. Talk to your doctor if:

  • You have heartburn at least twice a week for several weeks.
  • Food or acid often come back up into your throat.
  • You take antacid or h3 blockers, and you make changes like the ones described on this page, but your heartburn does not go away.

If your doctor thinks you need a PPI:

  • Ask to start with a low dose of generic prescription lansoprazole or omeprazole. You can also get these medicines over the counter.
  • If the heartburn gets better after a few weeks, talk to your doctor about gradually lowering your dose.

This report is for you to use when talking with your healthcare provider. It is not a substitute for medical advice and treatment.  Use of this report is at your own risk.

© 2017 Consumer Reports. Developed in cooperation with the American Gastroenterological Association.

05/2012

90,000 “Throwing in the heat.” Those vaccinated against the coronavirus honestly talked about everything

https://ria.ru/20201230/vaktsinatsiya-15

753.html

“It threw in a fever.” Those vaccinated against the coronavirus honestly told about everything

“I threw in a fever.” Those vaccinated against the coronavirus honestly told about everything – RIA Novosti, 07/27/2021

“It threw in a fever.” Those vaccinated against coronavirus honestly talked about everything

Mass vaccination against coronavirus is gaining momentum. The Sputnik V drug, developed by the Gamaleya Center, has already demonstrated its safety and high… RIA Novosti, 27.07.2021

2020-12-30T08: 00

2020-12-30T08: 00

2021-07-27T17: 01

science

vaccination

health

covid-19 coronavirus

coronavirus in russia

satellite v vaccine

epivaccoron vaccine

vaccination of Russians against covid-19

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https: // cdn25.img.ria.ru/images/07e4/0c/0f/1589334254_0:300:2726:1833_1920x0_80_0_0_eacca96aff29297d3ef28789ba298960.jpg

MOSCOW, Dec 30 – RIA Novosti, Alfiya Enikeeva. Mass vaccination against coronavirus is gaining momentum. Sputnik V, developed by the Gamaleya Center, has already demonstrated safety and high efficiency – 91.4 percent. Participants of post-registration tests and civil vaccination told RIA Novosti about how they felt after vaccination. Olga Shemonaeva, 52: “There was a desire to breathe out as soon as possible.” realistically assess the situation with the covid.In my opinion, everything is very serious. Among my acquaintances there are a lot of those who had very severe and sometimes fatal complications after this disease. Therefore, the decision to get vaccinated a long time ago. I even planned to participate in clinical trials, but I was stopped by the opportunity to receive a placebo. I am not a young girl, I am 52 years old. Overweight, there is a violation of glucose tolerance – this is not diabetes, but a condition that requires increased attention. These factors could aggravate the disease with natural infection.There was every chance not to slip through the easy option. In general, I was looking forward to the start of the mass vaccination. And on the very first day I signed up on the mos.ru website. I was a little worried before the vaccination. On the eve, the pressure has risen. But it was rather due to internal tension. The year turned out to be not easy – you are constantly in anxious anticipation, you listen to every sneeze. God forbid infecting elderly relatives. Therefore, there was a desire to breathe out as soon as possible, get the cherished antibodies and gain some confidence in the future.I was not afraid of the side effects of the vaccine itself. As far as I can imagine, Sputnik V has minimal risk. The drug was created on a well-known, tested platform. Yes, fever, flu-like syndrome, pain at the injection site are possible. But the manufacturer honestly warns about this, and, in my opinion, it is not difficult to survive. With the injection, no negative sensations – well, a little painful. It seemed to me that after about an hour – I was driving at that time – facial hyperemia appeared, that is, redness.Probably, the temperature has risen, I did not measure. Nothing more. Plus, the injection site reminded of itself for three days. And only when I accidentally lay down on my arm at night. Now I even have a feeling of a holiday. But I’m still careful, I go everywhere wearing a mask. I certainly advise acquaintances, friends and relatives to get vaccinated. To everyone who is ready to listen. Ruslan Khaitkulov, 32: “I signed up, I came, I did it.”But in any case, it’s better than nothing. If there is even a small chance that after this vaccination, immunity will form, why not take advantage of it? As far as I know, any serious post-vaccination complications are unlikely. These are very rare cases. My work involves communication with people – I teach at the university and at the lyceum at it. I would not like to accidentally infect anyone. Therefore, a week and a half ago, I signed up for the vaccination through the mos.ru website, came and made it. By the evening, the temperature rose slightly, there was a chill.One night I slept under the blankets, and the next day everything was in order. Until I feel completely protected, because only the first dose of the vaccine was injected. There will be a second in January. In any case, until I pass the antibody test, I will not be one hundred percent sure. Alfiya Maksutova, 33: “It’s better to sit with a temperature for a couple of days than to spend a couple of weeks on mechanical ventilation” I am a science journalist and, in principle, used to rely on scientific sources of information. I have been following the topic of vaccine development and discussion for a long time, reading the opinions of scientists.An article about Sputnik V appeared in the Lancet in September. I got acquainted with it and came to the conclusion that this drug is based on a long-known mechanism – such vector vaccines have been used for about 50 years. Yes, now it protects against covid, but the technology by which it was created is old, proven and reliable. She invited her husband and her dad to take part in clinical trials, which then began. My mother and I abstained because there was little data on health risk groups. The husband was not taken for testing.By that time, there were already enough 30-year-old male volunteers, but the 59-year-old dad was vaccinated. However, he had no side effects and we assumed he received a placebo. After the second dose of the drug, he also felt great. When, two weeks later, my father was tested for antibodies to the S-protein, he had a high titer. Naturally, there would be so many antibodies if he had been seriously ill, and we calmed down a bit. When the mass vaccination began, all adult family members signed up, except for the mother, who has a serious chronic illness.I myself have asthma, and, unfortunately, there is no information yet whether the vaccine has been tested on people like me. But I decided it was safe enough anyway. The side effects didn’t scare me. Still, a couple of days to sit with a temperature is much better than to spend a couple of weeks on mechanical ventilation. Only my brother and I had gotten after vaccination. Literally a couple of days I had a headache and my temperature was 37.3-37.5. Nothing more significant happened. But now we all feel much more confident. And as soon as the results of clinical trials appear in the group over 60 years old and people with serious chronic diseases, we will vaccinate the only adult in our family who remains unprotected – mom. Honestly, I thought I would have to wait for vaccinations for several weeks. But now you can sign up for any time. Unfortunately, people are afraid of vaccinations and don’t seem to be very active. But, as far as I understand, the biggest danger in the case of “Sputnik V” is that the vaccine for some reason will not work. Vladislav Strekopytov, 56 years old: “The end of voluntary imprisonment” “Coronavirus history” for me was the need to isolate myself. Due to an illness complicating COVID-19, I had to switch to telecommuting in April.Nine months without communication with family and friends is overkill. Therefore, when the vaccine was offered, I ran in the first rows to do it, and was vaccinated in a polyclinic on the Arbat. He came from the dacha, injected himself – and back. I received the first dose on December 11, January 4 will be the second. The vaccination itself is completely painless. I felt good when I was injected with it. The injection was given at 11 o’clock in the morning, and the reaction began at 6 o’clock in the evening: the temperature rose to 38. But the doctor warned me during vaccination that this happens in people over forty in 90 percent of cases.And it is true – of my friends who made Sputnik V, all of them had a high temperature on the first evening. At night I felt very bad, like with the flu – sometimes it was hot or cold. I was all sweaty and changed my clothes three times. Until the morning I drank four cups of tea with raspberries. My head ached very much. The next day everything was more or less normal. But in the evening the temperature rose again, although it was already lower – a little over 37. I had a headache again, and I went to bed early. On the third day there was no temperature, but my face turned red and my hands and ankles began to itch.There was also a feeling that the lymph nodes were swollen. On the fourth day, everything went away, no symptoms. I had no fear of getting sick with covid from the vaccine. I understood that they were not injecting us with a live virus. I was not afraid of side effects either. Every day, from morning to evening, I read about the coronavirus and the infection it causes: what happens to the sick, what complications, and so on. This is no joke, and it is clear that the pandemic will not end tomorrow. The only thing is not yet clear how long post-vaccination immunity lasts.But, at least, at least a little it will be possible to live in peace. Roman Maksimov, 30 years old: “I don’t want to put my elderly parents at risk” I have been thinking about vaccination for a long time. This was not a spontaneous decision. I already wanted to return to my usual way of life: go to the gym, meet with friends. So far I have limited almost all contacts. I rarely see my parents even. I don’t want to put them at risk because they are aged and chronic. We are wearing masks, of course, when I visit them, but all the same, my soul is restless.After the antibodies from the vaccine appear, I think it will be easier. I was vaccinated with “Sputnik V”. Before that, I read the available materials and realized that there was nothing wrong with it. Such vaccines have already been made – the technology was developed back in the Soviet Union – and they are effective. Of course, now no one knows what will happen in the long term, but for myself, I estimated the risks of vaccination much lower than the risks of getting sick. I have acquaintances who have nevertheless become infected with covid. They tolerated average. Honestly, I don’t want to be in their place at all.I was vaccinated on December 20th. When I was vaccinated, I thought: it finally happened. There was joy. But it’s too early to relax. I understand that after the first dose of the vaccine until February, when immunity develops, I am not protected. Therefore, so far nothing has changed globally in my life: I still sit at home, order food, rarely go outside. I had minor side effects after vaccination, but I would not even call them that. On the first day – weakness, light fog in the head. The temperature did not rise. The injection site did not hurt.For several days, with a sharp turn of the hand, I felt it, but it did not hurt. To be honest, I was preparing for the worst. My mom is a “Chronicle” and she is afraid while “Sputnik V” is vaccinated. Waiting for EpiVacCorona to enter civilian circulation. It is believed that there are not such serious restrictions. My father is in better health, he is going to get vaccinated right after the New Year. Among colleagues and friends, someone plans to get vaccinated in the near future, someone says: we will graft “.There is a certain inertia, someone is skeptical – we are all different. Of course, I would definitely recommend getting vaccinated. I think this is better than nothing. But everyone assesses their own risks.

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vaccination, health, covid-19 coronavirus, coronavirus in Russia, satellite v vaccine, epivaccorona vaccine, vaccination of Russians against covid-19

MOSCOW, Dec 30 – RIA Novosti, Alfia Enikeeva. Coronavirus mass vaccination gains momentum. Sputnik V, developed by the Gamaleya Center, has already demonstrated safety and high efficiency – 91.4 percent. Participants in post-registration trials and civil vaccination told RIA Novosti how they felt after vaccination.

Olga Shemonaeva, 52 years old: “There was a desire to breathe out as soon as possible”

By education I am a doctor, and I have the opportunity to understand information, separate truth from lies, realistically assess the situation with covid. In my opinion, everything is very serious. Among my acquaintances there are many who have had very severe and sometimes fatal complications after this disease.

Therefore, the decision to be vaccinated arose long ago. I even planned to participate in clinical trials, but I was stopped by the opportunity to receive a placebo.I am not a young girl, I am 52 years old. Overweight, there is a violation of glucose tolerance – this is not diabetes, but a condition that requires increased attention. These factors could aggravate the disease with natural infection. There was every chance not to slip through the easy option.

In general, I was looking forward to the start of mass vaccination. And on the very first day I signed up on the mos.ru website.

I was a little worried before vaccination. On the eve, the pressure has risen. But it was rather due to internal tension.The year turned out to be not easy – you are constantly in anxious anticipation, you listen to every sneeze. God forbid infecting elderly relatives. Therefore, there was a desire to breathe out as soon as possible, get the cherished antibodies and gain some confidence in the future.

December 25, 2020, 08:00 The whole truth about the vaccine against coronavirus

I was not afraid of side effects from the vaccine itself. As far as I can imagine, Sputnik V has minimal risk. The drug was created on a well-known, tested platform.Yes, fever, flu-like syndrome, pain at the injection site are possible. But the manufacturer honestly warns about this, and this, in my opinion, is not difficult to survive.

No negative sensations during injection – well, a little painful. It seemed to me that after about an hour – I was driving at that time – facial hyperemia appeared, that is, redness. Probably, the temperature has risen, I did not measure. Nothing more. Plus, the injection site reminded of itself for three days. And only when I accidentally lay on my hand at night.

Now I even have a feeling of a holiday. But I’m still careful, I go everywhere wearing a mask. I certainly advise acquaintances, friends and relatives to get vaccinated. Anyone who is willing to listen.

12 August 2020, 13:36 Infographics Sputnik V: the first registered vaccine against COVID-19

Infographics

View

Ruslan Khaitkulov, 32 years old: “Enrolled, came, did”

It is clear: so far there is little data, and we are not so sure in vaccines against coronavirus, as in all others. But in any case, it’s better than nothing. If there is even a small chance that after this vaccination, immunity will form, why not take advantage of it? As far as I know, any serious post-vaccination complications are unlikely. These are very rare cases.

My work involves communicating with people – I teach at the university and at the lyceum attached to it. I would not like to accidentally infect anyone. Therefore, a week and a half ago, I signed up for the vaccination through the mos.ru website, came and made it. By the evening, the temperature rose slightly, there was a chill.One night I slept under the blankets, and the next day everything was in order.

So far I do not feel completely protected, because only the first dose of the vaccine was administered. There will be a second in January. In any case, until I pass the antibody test, I will not be one hundred percent sure.

1 of 5

COVID-19 vaccine “Sputnik V” (“Gam-COVID-Vac”)

2 of 5

Employees load a container with Sputnik V COVID-19 vaccine at the National Center for Epidemiology and Microbiology named Gamalei in Moscow

3 of 5

Employee of the research laboratory of the biotechnological company BIOCAD in St. Petersburg.The Sputnik V vaccine is produced at its facilities.

Health workers during vaccination against coronavirus COVID-19 with the Sputnik V vaccine at the vaccination point of the city polyclinic No. 191, the head institution of the outpatient center GBUZ “GP No. 191 of the Moscow Department of Health”

5 of 5

Health workers during vaccination against coronavirus COVID-19 vaccine “Sputnik V” in the vaccination station of the city polyclinic No. 191, the head institution of the outpatient center GBUZ “State Enterprise No. 191 of the Department of Health of St.Moscow “

1 of 5

Vaccine against COVID-19″ Sputnik V “(” Gam-COVID-Vac “)

2 of 5

Microbiology named after Gamaleya in Moscow

3 of 5

An employee of the research laboratory of the biotechnological company BIOCAD in St. Petersburg, which produces the Sputnik V vaccine

4 of 5

A nurse holds a package with a coronavirus vaccine “Gam-Covid-Vac” in the city polyclinic No. 4 in Volgograd

5 of 5

Medical workers during vaccination against the coronavirus COVID-19 with the Sputnik V vaccine at the vaccination point of the city polyclinic No. 191, the head institution of the outpatient center GBUZ “GP No. 191 of the Department of HealthMoscow “

Alfiya Maksutova, 33 years old:” Better to sit with a temperature for a couple of days than to spend a couple of weeks on a ventilator “

I am a science journalist and, in principle, used to rely on scientific sources of information. An article about “Sputnik V” appeared in the Lancet in September and I came to the conclusion that this drug is based on a well-known mechanism – such vector vaccines have been used for about 50 years.Yes, now it protects against covid, but the technology by which it was created is old, proven and reliable.

Invited her husband and her dad to take part in clinical trials, which were then beginning. My mother and I abstained because there was little data on health risk groups. The husband was not taken for testing. By that time, there were already enough 30-year-old male volunteers, but the 59-year-old dad was vaccinated. However, he had no side effects and we assumed he received a placebo.Upset.

After the second dose of the drug, he also felt great. When, two weeks later, my father was tested for antibodies to the S-protein, he had a high titer. Naturally, there would be so many antibodies if he were seriously ill.

And we calmed down a bit. When the mass vaccination began, all adult family members signed up, except for the mother, who has a serious chronic illness. I myself have asthma, and, unfortunately, there is no information yet whether the vaccine has been tested on people like me.But I decided it was safe enough anyway. The side effects didn’t scare me. Still, a couple of days to sit with a temperature is much better than to spend a couple of weeks on a ventilator.

Only me and my brother had side effects after vaccination. Literally a couple of days I had a headache and my temperature was 37. 3-37.5. Nothing more significant happened. But now we all feel much more confident. And as soon as the results of clinical trials appear in the group over 60 years old and people with serious chronic diseases, we will vaccinate the only adult in our family who remains unprotected – mom.

Honestly, I thought I would have to wait for vaccinations for several weeks. But now you can sign up for any time. Unfortunately, people are afraid of vaccinations and don’t seem to be very active. But, as far as I understand, the biggest danger in the case of Sputnik V is that the vaccine, for some reason, will not work.

November 30, 2020, 12:29 pm The spread of coronavirus The expert explained the cases of COVID after vaccination with “Sputnik V”

Vladislav Strekopytov, 56 years old: “The end of the voluntary confinement” I needed to isolate myself.Due to an illness complicating COVID-19, I had to switch to telecommuting in April. Nine months without communication with family and friends is overkill.

Therefore, when the vaccine was offered, I ran in the forefront to do it.

Was vaccinated at the clinic on Arbat. He came from the dacha, injected himself – and back. I received the first dose on December 11, January 4 will be the second.

The vaccination itself is completely painless. I felt good when I was injected with it. The injection was given at 11 o’clock in the morning, and the reaction began at 6 o’clock in the evening: the temperature rose to 38.But the doctor warned me during vaccination that in people over forty in 90 percent of cases it happens. And it’s true – of my friends who made Sputnik V, everyone had a high temperature on the first evening.

At night I felt very bad, as with the flu – it was hot or cold. I was all sweaty and changed my clothes three times. Until the morning I drank four cups of tea with raspberries. My head ached very much. The next day everything was more or less normal. But in the evening the temperature rose again, however, already lower – just above 37. I had a headache again, and I went to bed early. On the third day there was no temperature, but my face turned red and my hands and ankles began to itch. There was also a feeling that the lymph nodes were swollen. On the fourth day, everything went away, no symptoms.

I was not afraid of getting sick with covid from vaccination. I understood that they were not injecting us with a live virus. I was not afraid of side effects either. Every day, from morning to evening, I read about the coronavirus and the infection it causes: what happens to the sick, what complications, and so on.This is no joke, and it is clear that the pandemic will not end tomorrow. The only thing is not yet clear how long post-vaccination immunity lasts. But, at least, at least a little it will be possible to live peacefully.

28 December 2020, 17:47 Spread of coronavirus Ginzburg spoke about the combination of Sputnik V and AstraZeneca vaccines

Roman Maksimov, 30: “I don’t want to put elderly parents at risk”

I have been thinking about vaccination for a long time. This was not a spontaneous decision. I already wanted to return to my usual way of life: go to the gym, meet with friends.So far I have limited almost all contacts. I rarely see my parents even. I don’t want to put them at risk because they are aged and chronic. We are wearing masks, of course, when I visit them, but all the same, my soul is restless. After the antibodies from the vaccine appear, I think it will be easier.

I was grafted with Sputnik V. Before that, I read the available materials and realized that there was nothing wrong with it. Such vaccines have already been made – the technology was developed back in the Soviet Union – and they are effective. Of course, now no one knows what will happen in the long term, but for myself, I estimated the risks of vaccination much lower than the risks of getting sick.I have acquaintances who have nevertheless become infected with covid. They tolerated average. Honestly, I don’t want to be in their place at all.

December 26, 2020, 12:42 pm Sputnik V coronavirus spread has shown an efficiency of over 90% for people over 60 years old

I was vaccinated on December 20. When I was vaccinated, I thought: it finally happened. There was joy. But it’s too early to relax. I understand that after the first dose of the vaccine until February, when immunity develops, I am not protected. Therefore, so far nothing has changed globally in my life: I still sit at home, order food, rarely go outside.

I had minor side effects after vaccination, but I would not even call them that. On the first day – weakness, light fog in the head. The temperature did not rise. The injection site did not hurt. For several days, with a sharp turn of the hand, I felt it, but it did not hurt. To be honest, I was preparing for the worst.

My mother is a “chronicler” and she is afraid while “Sputnik V” will be vaccinated. Waiting for EpiVacCorona to enter civilian circulation. It is believed that there are not such serious restrictions. My father is in better health, he is going to get vaccinated right after the New Year.

Among colleagues and friends, someone is planning to get vaccinated in the near future, someone says: “We will see for a couple of months how people will cope with the vaccination, and if everything is in order, then we will get vaccinated.” There is a certain inertia, someone is skeptical – we are all different. Of course, I would definitely recommend getting vaccinated. I think this is better than nothing. But everyone assesses their own risks.

Questions and answers on the topic “Obesity treatment”

Obesity is a chronic disease requiring long-term treatment

  • Obesity is recognized as a chronic disease requiring long-term treatment by various health organizations, including the World Health Organization (WHO) and the American Medical Association 1-3 .
  • Obesity is a complex multifactorial disease influenced by physiological, psychological, socioeconomic and genetic factors as well as environmental factors 4 .
  • Obesity is associated with decreased life expectancy and a variety of comorbidities, including type 2 diabetes, cardiovascular disease, hypertension, dyslipidemia 5.6 , sleep apnea syndrome 7 and some cancers 8.9 .Obesity is also associated with reduced physical activity and poor health-related quality of life 10-12 .
  • The risk of comorbidity and mortality increases with the severity of obesity 13 .

There are significant unmet medical needs in the treatment of obesity

  • Losing body weight by 5-10% has beneficial effects on the health of obese people, including improving blood glucose and cholesterol levels, blood pressure, and improving the condition of people with obstructive sleep apnea 14-18 .
  • Healthy eating and physical activity should be an integral part of any weight loss program, but this is not always enough to maintain the result 19 .
  • Maintaining a reduced body weight is challenging, in part due to metabolic changes in the body 19.20 .
  • Obesity is a complex disease, and therefore the patient needs to be offered several treatment options aimed at reducing body weight and maintaining the result and thus improving health 21 .

Type 1 glucagon-like peptide (GLP-1) regulates appetite and food intake

  • GLP-1 is a naturally occurring hormone released in response to food intake 22 . It regulates appetite and food intake by reducing hunger and increasing fullness and satiety after eating 23.24 .
  • GLP-1 also plays an important role in maintaining normal blood glucose levels by stimulating insulin release and suppressing glucagon secretion based on blood glucose levels 25 .
  • The regulating effect of GLP-1 on appetite and blood pressure has therapeutic potential for treating obese people 26 .

Novo Nordisk is committed to improving the quality of obesity care

  • Novo Nordisk is committed to improving the quality of obesity care through the introduction of new treatment methods and tools, as well as support programs created by listening carefully to obese people and learning from them and those who support them.
  • In the long term, we aim to use our rich experience to help obese people. We are paving the way for innovative treatments for obese people.

QUESTIONS AND ANSWERS

Basic information on obesity

1. What is obesity?

2. How is the severity of obesity measured?
3. What is the prevalence of overweight and obesity?
4. What is the current level of obesity diagnosis?
5.How does obesity affect people?
6. What is the societal burden of obesity?
7. Is obesity just a lifestyle problem?
8. What is the medical rationale for treating obesity?
9. What health professionals treat obesity?
10. What comorbidities are associated with obesity?
11. How are obesity and type 2 diabetes related?
12. How many obese people have type 2 diabetes in Russia?
13.How is prediabetes determined?
14. How are obesity and cardiovascular disease related?
15. How obesity and hypertension are related?
16. How are obesity and dyslipidemia related?
17. What is obstructive sleep apnea (OSA)?
18. How are obesity and OSA related?
19. Can weight loss improve people with OSA?
20. How is OSA usually treated?
21. What is the natural physiological role of GLP-1 in appetite regulation?
22.What is appetite?
23. Why is appetite regulation so important?
24. How are the brain and intestines related to the regulation of appetite?
25. How do gut hormones, including GLP-1, alter the periods of time before and after meals?
26. Why did Novo Nordisk decide to enter a new therapeutic area of ​​obesity treatment?
27. What is Saxenda®?
28. How does Saxenda® work for obese people?
29. How does Saxenda® (liraglutide 3 mg) affect appetite regulation?
30.Does Novo Nordisk research and develop drugs for the treatment of obesity?
31. How was Saxenda®
studied 32. How does Saxenda® affect weight loss?
33. In addition to weight loss, what other effects does Saxenda® have?
34. How much weight loss that Saxenda® provides can affect the patient’s health?
35. What are the most common side effects caused by Saxenda®?
36. What device will be used to administer Saxenda®?
37.In which countries is Saxenda® registered?
38. What indication for the use of Saxenda® is registered in Russia?
39. What to do if body weight does not decrease during therapy with Sakenda®?
40. What drugs for the treatment of obesity are present on the Russian market at the moment?
41. How does Saxenda® differ from other drugs for the treatment of obesity?
42. Can Saxenda® be used in combination with other drugs for the treatment of obesity?
43.Why is there a need for pharmacotherapy?
44. Why is there a need for pharmacotherapy if bariatric surgery is showing good results in weight loss?

Definition and Measurement

1. What is obesity?

Obesity is a chronic condition that requires long-term treatment. It is a complex and multifactorial disease that is influenced by physiological, psychological, environmental, socioeconomic and genetic factors 4 .

Obesity is recognized as a chronic disease by many health organizations, including the World Health Organization (WHO) and the American Medical Association1,3,39 and is defined as excess fat accumulation that poses a health risk 40 .

2. How is the severity of obesity measured?

Usually, the severity of obesity is measured using the body mass index (BMI), which is an estimate of the amount of fat in a person’s body in relation to their body weight and height.Table 1) 4 . Obesity is classified as a BMI ≥30 kg / m2 2 , and is further subdivided into three classes (class I, II, III) depending on how much BMI is higher than 30 kg / m2 2 .

BMI has its limitations – it does not differentiate between fat and lean body mass (eg muscle) and therefore can lead to overestimation or underestimation of body fat in some people 41 . Alternative ways to measure the amount of body fat: measuring the waist circumference and the waist-to-hip ratio.

Table 1. Classification of overweight / obesity by BMI

Classification BMI (kg / m 2 )
Deficit of body weight <18.5
Normal body weight ≥18.5 and <25
Overweight ≥25 and <30
Obesity ≥30
Obesity I degree ≥30 and <35
Obesity II degree ≥35 and <40
Obesity III degree ≥40

Prevalence

3.What is the prevalence of overweight and obesity?

The prevalence of obesity is growing at an alarming rate on all continents; the percentage of obese people has almost doubled since 1980 40 . According to WHO, obesity has reached pandemic proportions: more than 1.9 billion adults (> 18 years old) are overweight (BMI ≥25 kg / m2 2 ) 40 . More than 600 million of them are obese (BMI ≥30 kg / m2 2 ) 40 .

The global rise in the prevalence of obesity is a problem affecting the health systems of many countries and at a significant cost to the health system 40.42 . In Russia, approximately 27% of the adult population, or about 38 million people, are obese 43 .

Obesity is associated with reduced life expectancy and a variety of comorbidities, including type 2 diabetes, cardiovascular disease, hypertension, dyslipidemia 5.6 , sleep apnea syndrome 7 , some cancers 8.9 and diseases gallbladder 45 .Obesity is also associated with decreased physical activity 10 and a deterioration in health-related quality of life11,12.

The risk of comorbidity and mortality increases with the severity of obesity13. Although not all obese people have health problems, comorbidities are usually more common in people with a BMI of 35 kg / m2 2 and above (grade II and III obesity) 6 .

Reducing body weight by 5-10% has a beneficial effect on the health of obese people, including normalizing blood glucose and cholesterol levels, blood pressure and improving the condition of people with obstructive sleep apnea 14-18 .

Obesity is a complex disease, and therefore the patient needs to be offered several treatment options aimed at reducing and maintaining body weight and thus improving health 21 .

4. What is the current level of obesity diagnosis?

The obesity diagnosis rate remains inadequate and the obesity prevalence estimate is still understated at 46.47; According to the Ministry of Health of the Russian Federation, in Russia less than 1% of patients with BMI from 30 to 40 kg / m2 are diagnosed with obesity48.

Obesity treatment

5. How does obesity affect people?

Obesity is a chronic disease that requires long-term treatment. It has many serious health consequences and is associated with reduced life expectancy 5.49 . The risk of comorbidity and mortality increases with the severity of obesity 5.49 . It is a complex multifactorial disease that is influenced by genetic, physiological, environmental and psychological factors.

Obesity is associated with many serious comorbidities, including type 2 diabetes, heart disease, hypertension, increased cholesterol and triglyceride levels, obstructive sleep apnea, and certain cancers 10,26,35,36 . More than half of people with a BMI of 35 kg / m2 2 and above (obesity II and III degrees) have increased glucose levels 50 . Regardless of the initial body weight, maintaining a 5-10% weight loss result has a beneficial effect on the health of obese people 51 , and has been shown to slow and / or prevent the development of type 2 diabetes 17.52 .

6. What is the societal burden of obesity?

Obesity is a complex multifactorial disease characterized by excessive accumulation of fat, which entails many consequences for various organs and systems of the body. In addition to the impact of obesity on the health of the individual, the global rise in the prevalence of obesity is also a health problem in many countries, with enormous costs to health systems.In Russia, approximately 27% of the adult population, or about 38 million people, are obese 43

7. Is obesity just a lifestyle problem?

In June 2013, the American Medical Association (AMA), the largest medical community in the United States, officially recognized obesity as a disease to change the medical community’s approach to treating obese people and improve treatment outcomes, especially in people with obesity-related comorbidities. 39 .This policy change by the AMA was an important step towards improving the quality of obesity care and has been recognized by other leading professional and patient associations, including the World Health Organization.

Despite this, obesity is still perceived as a lifestyle choice rather than a disease, because we can choose what to eat. However, we can also choose not to smoke, exercise, or drink less – and yet lung cancer, cardiovascular disease, and cirrhosis of the liver are considered diseases.

8. What is the medical rationale for treating obesity?

Obesity is associated with serious comorbidities, including type 2 diabetes, heart disease, high blood pressure, high cholesterol and triglyceride levels, obstructive sleep apnea, and certain cancers 5,21,56,57 . More than half of people with a BMI of 35 kg / m2 2 and above (obesity II and III degrees) have increased glucose levels 50 .Regardless of initial body weight, sustained weight loss of 5-10% is beneficial for obese people and has been shown to slow and / or prevent the development of type 2 diabetes 58-60 .

9. What health professionals treat obesity?

Obesity treatment, including medication, is dealt with by a variety of specialists – primarily endocrinologists, but it can also be therapists, gastroenterologists, nutritionists, andrologists, gynecologists, cardiologists and somnologists.

Obesity-related comorbidities

10. What comorbidities are associated with obesity?

Obesity is a multifactorial chronic disease that is associated with many serious comorbidities, including hypertension, prediabetes, type 2 diabetes mellitus, dyslipidemia 5.6 , some cancers 8.9 , obstructive sleep apnea 7 , and also reduced life expectancy 5.49 .Obese people also suffer from physical symptoms (eg joint pain, urinary incontinence), limited physical activity (eg limited mobility) and psychosocial problems (eg disorders of body awareness or depression). More than half of people with a BMI of 35 kg / m2 2 and above (obesity II and III degrees) have increased glucose levels 50 .

Type 2 diabetes mellitus

11. What is the relationship between obesity and type 2 diabetes?

Type 2 diabetes mellitus is a common comorbid condition in obese people 4 .The mechanisms underlying this relationship are not clearly defined; however, insulin resistance, which is often seen in obese people, plays a key role 56 . Excessive accumulation of fatty tissue in the abdomen is also one of the main risk factors 65 .

12. How many obese people have type 2 diabetes in Russia?

Obesity is closely related to the development of type 2 diabetes mellitus 4 .The prevalence of diabetes mellitus among people with a body mass index (BMI) of 35 kg / m2 2 and higher in Russia is 57.8% 66 .

13. How is prediabetes determined?

Prediabetes is an increase in blood sugar levels to borderline values ​​in humans; this is no longer the norm, but not yet diabetes mellitus. Prediabetes is one of the main risk factors for developing diabetes. It is also known as impaired glucose tolerance, or dysglycemia.A very indicative indicator of blood sugar levels is the level of glycated hemoglobin (HbA 1c ) in the blood. This indicator can also be diagnosed.

Cardiovascular diseases

14. How are obesity and cardiovascular disease related?

Obesity directly affects the cardiovascular system and is associated with numerous heart complications, including congestive heart failure, arrhythmias (heart rhythm disturbances), coronary heart disease and stroke 69 .In particular, obesity increases the risk of heart disease due to 69 :

  • Increase in the level of cholesterol and triglycerides in the blood 90 240

  • Lowering the level of high-density lipoprotein cholesterol (HDL; “good” cholesterol) 90 240

  • Increase in blood pressure
  • Prediabetes / Diabetes Mellitus
  • Obstructive sleep apnea 70

Obesity and overweight are also independent risk factors for myocardial infarction and coronary heart disease (coronary artery disease) 71 , the leading cause of death worldwide 72 .

15. How are obesity and arterial hypertension related?

Arterial hypertension (high blood pressure) is a common comorbid condition in obese people, and the link is well established. High blood pressure is more common among obese people compared to people who are not obese. The mechanism underlying why obesity directly causes hypertension is not clearly defined 73 .

16. How are obesity and dyslipidemia related?

Dyslipidemia (abnormal lipid profile) is a common comorbid condition in obese people. Obesity affects blood lipid levels, which leads to an increased risk of cardiovascular disease. Typically, obese people have elevated fasting plasma triglycerides, high low-density lipoprotein cholesterol, and low HDL (“good”) cholesterol 49.73 .

Obstructive sleep apnea

17. What is obstructive sleep apnea (OSA)?

OSA is a common sleep-breathing disorder that affects 2 to 5% of people in the age group from 30 to 60 years old in Russia 74.75 . It is characterized by a decrease or complete cessation of air flow during breathing. OSA symptoms include daytime sleepiness, having to wake up at night to urinate, decreased sex drive, restless sleep, and snoring 90 238 74 90 239.The diagnosis of OSA is usually made by a somnologist after somnography – a special study that is performed at night.

The most common cause of OSA is overweight and obesity: 60-90% of people with OSA are overweight or obese 76 .

OSA is also associated with an increased risk of hypertension, stroke, insulin resistance, metabolic syndrome, type 2 diabetes mellitus, decreased quality of life, increased risk of road traffic accidents, and increased risk of sudden death 77-80 .

18. How are obesity and OSA related?

Obesity is associated with several complications for the respiratory system, including OSA, due to increased demand for ventilation and respiratory load, decreased reserve ventilation capacity, and closure of the peripheral lungs 82 .

Obese people also have excess fat around the neck and chest, which puts additional stress on the larynx and chest when the muscles are relaxed during sleep.Fat deposits can also build up in the throat, narrowing the air passage. These factors can weaken or completely block air flow during sleep 76 .

19. Can weight loss improve people with OSA?

It is recommended that people who are overweight or obese who have been diagnosed with OSA be encouraged to lose weight. Weight loss in people with OSA is believed to result in symptom relief 83 .

20. How is OSA usually treated?

Continuous positive airway pressure (CPAP) is a common treatment for people with moderate to severe OSA. This is a mask that covers the mouth or nose and mouth, to which a pump is connected, which provides a continuous supply of compressed air, which prevents the larynx from closing during sleep 83 .

The use of GLP-1 in the treatment of obesity

Mechanism of action

21.What is the natural physiological role of GLP-1 in appetite regulation?

GLP-1 is a naturally occurring hormone released in response to food intake 22 . It regulates appetite and food intake by reducing hunger and increasing fullness and satiety after eating 22.23 .

GLP-1 also plays an important role in maintaining normal blood glucose levels by stimulating insulin release and suppressing glucagon secretion based on blood glucose levels 25 .

The regulating effect of GLP-1 on appetite and blood pressure has therapeutic potential for treating obese people 26.84 .

Appetite regulation

22. What is appetite?

Appetite is the desire to consume food, it manifests itself in the form of a physical feeling of hunger. Appetite regulation is a complex process involving several hormones that transmit signals from the gut to the brain.

23. Why is appetite regulation so important?

Appetite regulation is important for maintaining a healthy body weight, while hunger exists to ensure that people consume enough nutrients to meet the body’s needs. A dysregulated appetite can lead to wasting or obesity, both of which have serious health consequences.

24. How are the brain and intestines related to the regulation of appetite?

Both the brain and intestines play an important role in appetite regulation.After a meal, the gut detects and reacts to the presence of food by producing several hormones / peptides such as ghrelin, leptin and GLP-1. They enter the brain and stimulate the feeling of satiety or hunger, thus controlling food intake 85 .

25. How do gut hormones, including GLP-1, alter the periods of time before and after meals?

After a meal, the levels of hormones responsible for feeling hunger decrease and the levels of hormones responsible for feeling full stomach (satiety) in response to an increase in glucose levels increase.Before a meal, the opposite is true – the levels of hunger hormones gradually rise and the levels of satiety hormones decrease, which stimulates food intake.

GLP-1 levels rise sharply in response to an increase in postprandial blood glucose levels. GLP-1 causes the saturation center in the brain to be stimulated. At the same time, GLP-1 stimulates the release of insulin and suppresses the release of glucagon, which lowers the blood sugar level, it is important that if the blood sugar is normal, it does not decrease. 86

Significant differences were found between the levels of the hormone in the gut in obese and normal weight people. Also, responses to hunger and satiety hormones are less pronounced, which affects both the increase and maintenance of body weight in obese people 86.87 .

Obesity and Novo Nordisk

26. Why did Novo Nordisk decide to enter a new therapeutic area of ​​obesity treatment?

Novo Nordisk is committed to discovering and developing new innovative treatments that will help people suffering from chronic diseases.

Obesity is a disease associated with many serious comorbidities, including obstructive sleep apnea, heart disease, type 2 diabetes, high blood pressure, high cholesterol and triglyceride levels, atherosclerosis, and certain cancers 5,21,56,57 .

Current pharmacotherapy options are limited, and we believe there is a need for new therapies to help adults who fight obesity and obesity-related comorbidities, thereby improving their health and reducing complications.

We have long been a global leader in the treatment of diabetes and other chronic diseases, and therefore we believe that we have the right combination of experience, knowledge and innovation to improve our understanding of obesity and its treatment.

Brief information on Saxenda®

27. What is Saxenda®?

Saxenda® (liraglutide 3 mg) is an analogue of glucagon-like peptide-1 (GLP-1), 97% identical to natural human GLP-1 – an intestinal hormone involved in the regulation of appetite 27 – for use once a day.

28. How does Saxenda® work for obese people?

Saxenda® (liraglutide 3 mg), an analogue of glucagon-like peptide-1 (GLP-1) involved in the regulation of appetite, for use once a day, reduces body weight by reducing food intake. Saxenda® does not increase the 24-hour energy expenditure 36 .

In addition, Saxenda® stimulates the release of insulin and suppresses the secretion of glucagon, depending on the level of glucose in the blood, if necessary.These properties of the drug allow it to lower blood glucose levels 36 .

29. How does Saxenda® (liraglutide 3 mg) affect appetite regulation?

Saxenda® binds to the GLP-1 receptors in the brain, which are involved in the regulation of appetite, and activates them. Receptor activation induces satiety, thus controlling food intake 85 .

In Russia, Saxenda® is indicated for use in combination with a low-calorie diet and increased physical activity for the treatment of chronic obesity in adults with a baseline body mass index (BMI) of 164:

  • ≥ 30 kg / m2 2 and above (obesity) or
  • ≥ 27 kg / m2 2 to <30 kg / m2 2 (overweight) with at least one overweight-related comorbidity, such as prediabetes, type 2 diabetes, hypertension, dyslipidemia, or syndrome obstructive sleep apnea.

The instructions for medical use of Saxenda® in Russia say that treatment should be discontinued if the patient has not achieved 5% weight loss after 12 weeks at a dose of 3 mg per day), since the likelihood that the patient will achieve clinically significant weight loss and maintain the result with continued treatment is very low 164 .

30. Does Novo Nordisk conduct research and develop drugs for the treatment of obesity?

Yes.Novo Nordisk is committed to discovering, developing and implementing new innovative methods and treatment tools in order to improve the lives of people suffering from chronic diseases.

The new Obesity Research and Development Center in Seattle, USA, announced on September 25, 2014, will illustrate Novo Nordisk’s commitment to discovering, developing and deploying new treatments for obesity. A motivated team of obesity researchers will work to identify new drug targets and improve the scientific understanding of existing therapeutic targets.

31. How Saxenda® was investigated

Saxenda® has been studied in large-scale international clinical trials. The drug research program included 4 studies –

SCALE ™ Study Obesity and Prediabetes

Research SCALE ™ Maintain

SCALE ™ Study Diabetes Mellitus

SCALE ™ Study Sleep Apnea

More than 5,000 patients were included in the studies.The follow-up period ranged from 6 months to three years.

32. How does Saxenda® affect weight loss?

Clinical studies of Saxenda® have shown that in most (9 out of 10) patients, the drug leads to weight loss. The largest study SCALE obesity and prediabetes in people treated with Saxenda® in combination with diet and exercise and completed the 56-week treatment period, there was a decrease in body weight by 9.2% Most patients treated with Saxenda® responded to treatment 28.99 .

  • 63% of obese patients treated with Saxenda® achieved a clinically significant weight loss, i.e., weight loss ≥5% of baseline body weight compared to 27% in the placebo group (p <0.0001) 90 240
  • 33% of obese patients treated with Saxenda® achieved a weight loss of> 10% from baseline, compared with 11% in the placebo group 90 240

  • 69% of obese patients with high blood sugar (prediabetes) returned to normal blood sugar levels when using Saxenda® 31 .

33. In addition to weight loss, what other effects does Saxenda® have?

In addition to weight loss, Saskenda® has a number of positive effects – taking the drug lowers blood pressure, lowers cholesterol levels, and normalizes breathing in the presence of sleep apnea. During therapy, the waist circumference decreased. It has also been shown that Saxenda mainly reduces the amount of fat around the internal organs, the so-called visceral fat., which is very important for the prevention of complications of obesity

34. To what extent can the decrease in body weight provided by Saxenda® affect the patient’s health?

5-10% weight loss in obese people brings significant health benefits, including improvements in blood glucose, blood pressure, cholesterol levels 14 and improvement in obstructive sleep apnea 15-18

35.What are the most common side effects caused by Saxenda®?

Throughout the clinical development program, Saxenda® was generally well tolerated 104 . The most common side effects were from the gastrointestinal tract: for example, nausea, vomiting, diarrhea, and constipation; they were not heavy and were of a transient nature 94, 97 .

In most cases, these phenomena disappeared within four weeks.

Nausea is a common side effect with all drugs in this group and is usually seen early in treatment.

Novo Nordisk carefully monitors the safety of patients and constantly monitors adverse events associated with the use of its drugs.

36. What device will be used to administer Saxenda®?

Saxenda® is administered by subcutaneous injection using a device called a multi-dose disposable pen.

The Saxenda® pen is the latest in pre-filled drug delivery devices from Novo Nordisk. This pen is a multi-option, user-friendly pen designed to make your daily injections easy. These options include an easy-to-read dose counter, ergonomic design, and a dedicated click sound to confirm dose setting.

37. In which countries is Saxenda® registered?

Saxenda® is the first analogue of human glucagon-like peptide-1 (GLP-1), registered for use in the treatment of obesity in the USA, EU, Canada and Russia. 34.36.164

38. What indication for the use of Saxenda® is registered in Russia?

The Ministry of Health of the Russian Federation has registered the drug Saxenda® (liraglutide 3 mg) as an adjunct to a low-calorie diet and increased physical activity for long-term use to correct body weight in adult patients with BMI: ≥ 30 kg / m 2 (obesity) or ≥ 27 kg / m2 2 up to <30 kg / m2 2 (overweight) with at least one overweight-related co-morbidity, such as prediabetes, type 2 diabetes, hypertension, dyslipidemia, or obstructive sleep apnea in a dream.

39. What to do if body weight does not decrease during therapy with Sakenda®?

The instructions for medical use of the drug indicate that doctors should evaluate the change in body weight 12 weeks after starting the use of Saxenda® at a dose of 3.0 mg. If the patient’s body weight has not decreased by at least 5% of the original Saxenda® drug is canceled, since the likelihood that the patient will achieve clinically significant weight loss and maintain the result while continuing treatment is very low.

40. What drugs for the treatment of obesity are present on the Russian market at the moment?

If obese people are unable to lose weight through diet and exercise alone, there are a number of pharmacotherapy options that work through different mechanisms. Currently registered drugs include:

  • Orlistat and preparations based on it , inhibits the absorption of fats from food by blocking the enzyme that breaks down fats
  • Sibutramine and preparations based on it Available only in Russia and a limited number of countries.It is a selective inhibitor of the reuptake of serotonin and norepinephrine, enhances the feeling of satiety, increases the body’s energy consumption.

Another way to lose weight is bariatric surgery, which is only used as a last resort. Weight loss surgery is only recommended for people with a BMI> 40 kg / m2 2 or 35-40 kg / m2 2 with a serious underlying medical condition (eg, type 2 diabetes).However, surgery is expensive and risky. According to current guidelines, the decision about surgery should be made after two unsuccessful attempts at conservative treatment.

41. How does Saxenda® differ from other drugs for the treatment of obesity?

A direct comparison was made between Saxenda® and orlistat. Patients who received Saxenda® therapy, 1 year after starting treatment in combination with diet and exercise, lost 3.8 kg more than people who took orlistat. 91.92

No direct comparisons have been made for sibutramine. It should be noted that a large-scale study of sibutramine, called SCAUT, revealed an increase in the incidence of heart attacks and strokes in patients receiving the drug, and led to the withdrawal of the drug sibutramine from the market in most countries. In a number of countries (including the Russian Federation), sibutramine has remained on the market under various brand names.

42. Can Saxenda® be used in combination with other drugs to treat obesity?

The efficacy and safety of Saxenda® in combination with other drugs for the treatment of obesity has not been studied in the SCALE ™ clinical development program.Accordingly, the combination of Saxenda® with other drugs for the treatment of obesity is a contraindication.

43. Why is there a need for pharmacotherapy?

Most often, obesity begins to be treated with diet and physical activity, but if it is possible to achieve a result, it is usually short-lived. The reason is the ancient mechanisms of our body, aimed at preserving the accumulated fat. Once upon a time, with a lack of food at the dawn of human history, this was a necessary condition for survival.The situation has changed, but the mechanism has remained. Therefore, when BMI rises to 27 or more in the presence of complications, obesity, or to 30 or more, regardless of the presence of complications, international recommendations for the treatment of obesity recommend starting drug therapy. But what drug to prescribe – only the doctor decides.

44. Why is there a need for pharmacotherapy if bariatric surgery shows good results in weight loss?

Bariatric surgery has been shown to be highly effective in reducing body weight in most severely obese patients.However, bariatric surgery carries significant risks and not all patients want to undergo surgery.

In addition, there are certain criteria for identifying patients for whom surgery is indicated (for example, BMI ≥ 40 kg / m2 2 without concomitant diseases or ≥35 kg / m2 2 with serious concomitant diseases). 4.141 In most countries, only a small proportion of patients qualify for bariatric procedures.

In most current guidelines, the decision to perform bariatric surgery is considered only after unsuccessful attempts at conservative treatment.

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90,000 Capsaicin for non-allergic rhinitis | Cochrane

Review Question

Is capsaicin, when taken intranasally (nasally), in the treatment of non-allergic rhinitis compared to no therapy, placebo, or other topical or systemic drugs?

Relevance

Rhinitis (runny nose) means inflammation of the mucous membrane (inner) lining of the nose.It affects between 30% and 40% of the total population. There are many forms of rhinitis: rhinosinusitis (or simply sinusitis), allergic rhinitis, and non-allergic rhinitis. Non-allergic rhinitis is diagnosed in patients who have negative allergy test results and do not have sinusitis. Symptoms include nasal congestion, a feeling of a blockage or blockage in the nose causing difficulty breathing, clear nasal discharge (runny nose), sneezing, and itching in the nose. There are several subtypes of non-allergic rhinitis: occupational (from exposure to chemicals), smokers’ rhinitis, edible rhinitis (associated with food or fluid intake), hormonal rhinitis (associated with changes in hormone levels in the body), rhinitis of pregnancy, senile rhinitis or rhinitis of the elderly (mainly found in the elderly), drug-induced rhinitis (for example, with overuse of nasal sprays for nasal congestion) and local allergic rhinitis (local allergy in the nose when skin tests or blood tests for allergies are negative).The most common subtype of non-allergic rhinitis is “idiopathic” or “vasomotor” rhinitis, which occurs as a result of an imbalance in the nervous system (nerve) that controls the nasal system. The mechanisms of development of many of these subtypes remain unknown. Non-allergic rhinitis affects approximately 25 % – 50% of patients with rhinitis, and thus it is a very common disease.

Capsaicin is the active ingredient in hot peppers (chili).It has medicinal properties and is used in other areas of medicine, such as neuralgia (pain associated with nerve damage) and psoriasis (skin disease). Side effects with intranasal (nasal) use of capsaicin include irritation, burning, sneezing, and coughing, but there are no known long-term side effects of capsaicin. Capsaicin is given as a short-term application, usually for one day. It works by decreasing the expression (down-regulation of expression) of the transient receptor potentials of vanilloid (TRPV) receptors on C-sensory fibers.TRPVs are special ion channels involved in the generation of sensations of pain, cold, heat, tastes, pressure and vision. C-fibers help conduct some of these sensations. Research is ongoing on the effects of capsaicin on these mechanisms and its clinical use.

Research characteristics

We included four studies with 302 patients with idiopathic non-allergic rhinitis. All included in the review studies described patients with moderately severe idiopathic non-allergic rhinitis between the ages of 16 and 65 years.The follow-up period in the included studies ranged from four to 38 weeks after treatment.

Main results

Individually, each study reported that overall nasal function in patients with non-allergic rhinitis improved with capsaicin treatment compared with placebo. It also appears that capsaicin works better than another commonly used nasal drug (topical nasal drug), budesonide (a steroid).The best knowledge we have on capsaicin treatment supports using it five times in one day and using a dose of at least 4 micrograms per breath. We were unable to combine the results into a single analysis. The studies included in the review did not provide enough information to allow us to conclude on side effects. We also wanted to include other outcomes in the review (eg, quality of life, treatment failure, endoscopic measurements, turbinate or mucosal size, cost of therapy), but none of these outcomes were assessed or reported in the included studies.

Quality of evidence

Overall, we rated the quality of the evidence as low to moderate. This evidence is current to June 2015.

Conclusions

Given that many other treatment options do not work well for non-allergic rhinitis, capsaicin is a reasonable option to try under medical supervision.

Somatuline Autogel instructions for use: indications, contraindications, side effects – description Somatuline Autogel gel for long-term administration.action 120 mg: syringe 1 pc. in set with needle (22042)

Acromegaly

The recommended starting dose is 120 mg every 28 days.

Patients who have achieved effective control over the disease during therapy with somatostatin analogues can be prescribed Somatulin ® Autogel ® at a dose of 120 mg with an increased interval – every 42-56 days. In these patients, clinical symptoms and levels of GH and IGF-1 should be monitored regularly and in the long term.

All patients are shown regular monitoring of clinical symptoms, GH and IGF-1 levels.

Carcinoid tumors

The recommended starting dose is 120 mg every 28 days. In the future, the dose should be selected depending on the achieved reduction in symptoms.

Patients who have achieved effective control over the disease during therapy with somatostatin analogues can be prescribed Somatulin ® Autogel ® at a dose of 120 mg with an increased interval – every 42-56 days.

Rules of administration of the drug

Gel for subcutaneous administration of prolonged action is supplied in a pre-filled syringe equipped with a protective device that automatically closes the needle immediately after the injection, thereby helping to prevent accidental needle sticking after use.

The drug should be injected deeply s / c immediately after opening the package.

1 syringe with the drug is intended for single administration only.

The drug is injected by medical personnel into the upper lateral quadrant of the buttock.

If the patient receives a stable dose of the drug Somatulin ® Autogel ® , injections can be carried out at home by the patients themselves or their relatives after prior appropriate training from a doctor. When self-administered by the patient, the drug should be injected into the upper thigh.

When administering the drug, the following instructions should be observed.

1. Take Somatulin ® Autogel ® out of the refrigerator 30 minutes before use.

2. Make sure there is a clean preparatory area and wash your hands.

3. Before opening, check the integrity of the package containing the syringe with the preparation. Also, you need to make sure that the drug has not expired. The expiration date is shown on the package label. Do not use the drug in case of violation of the integrity of the package or after the expiration date.

4. Open the bag and remove the syringe with the protective device from it.

5. Choose a site for the proposed injection. Disinfect the intended injection site (upper thigh or upper lateral quadrant of the buttock), avoiding rubbing the skin. The injection is done alternately each time, then in the left, then in the right buttock or thigh.

6. Turn and pull the piston travel guard, then remove it.

7. Remove the needle cap.

8.Insert the needle into the upper thigh or upper lateral quadrant of the buttock without grasping the skin fold, but holding the skin with your thumb and forefinger.

The needle should be inserted quickly, full length, perpendicular to the skin surface (deep subcutaneous injection).

9. Slowly inject the entire drug, applying constant, even pressure on the plunger, while leaving the needle stationary (usually, it takes about 20 seconds to fully administer the drug). At the moment when the piston completely passes the entire body of the syringe and abuts against the opposite end, a click is heard.

Note: the piston must be kept pressed in order to avoid triggering the safety device.

10. While holding the plunger, remove the needle from the injection site.

11. After that, release the piston, the needle will automatically be pulled into the tube of the safety device and locked in it.

12. Gently apply a dry cotton pad or sterile tissue to the injection site to avoid bleeding. Do not rub or massage the injection site after injection.

13. Dispose of the used syringe according to the instructions.

90,000 Type 1 diabetes – New treatments

Immunotherapy

Type 1 diabetes is an autoimmune disease that is modulated by cytotoxic T cells. Several drugs are being tested to treat the first manifestation of the disease. Nonspecific antigenic systemic immunotherapy, including T cell suppressors (cyclosporine), antiproliferative drugs (methotrexate, azathioprine), and antithymocyte globulin have shown a significant trend towards side effects.Although the use of cyclosporine did reduce the required insulin dose for a short time, the drug causes nephrotoxicity, and the effect on beta cells weakened with discontinuation of treatment. Specific antigen vaccination with recombinant glutamate decarboxylase (GAD) demonstrated an increase in stimulated C-peptide within 3 months of treatment after diagnosis. [93] Ludvigsson J, Faresjö M, Hjorth M, et al. GAD treatment and insulin secretion in recent-onset type 1 diabetes.N Engl J Med. 2008 Oct 30; 359 (18): 1909-20.
https://www.nejm.org/doi/full/10.1056/NEJMoa0804328

http://www.ncbi.nlm.nih.gov/pubmed/18843118?tool=bestpractice.com
Clinical trials are ongoing for the treatment of type 1 diabetes using dendritic cells, mesenchymal stem cells, cord blood transfusions, and immunomodulators that are now approved for the treatment of other diseases such as granulocyte colony-stimulating factor (G-CSF) or tumor necrosis factor inhibitors -alpha.[94] Rewers M, Gottlieb P. Immunotherapy for the prevention and treatment of type 1 diabetes: human trials and a look into the future. Diabetes Care. 2009 Oct; 32 (10): 1769-82.
http://care.diabetesjournals.org/content/32/10/1769.long

http://www.ncbi.nlm.nih.gov/pubmed/19794002?tool=bestpractice.com

Teplizumab

One clinical trial of the anti-CD3 monoclonal antibody, teplizumab, in new-onset diabetes patients showed that the decline in beta cell function (as measured by C-peptide) was slowed down and the insulin requirement for glycemic control was reduced.[95] Sherry N, Hagopian W, Ludvigsson J, et al. Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomized, placebo-controlled trial. Lancet. 2011 Aug 6; 378 (9790): 487-97.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC31

/

http://www.ncbi.nlm.nih.gov/pubmed/21719095?tool=bestpractice.com
[96] Hagopian W, Ferry RJ Jr, Sherry N, et al. Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protégé trial.Diabetes. 2013 Nov; 62 (11): 3901-8.
https://www.doi.org/10.2337/db13-0236

http://www.ncbi.nlm.nih.gov/pubmed/23801579?tool=bestpractice.com
In one study in non-diabetic patients who were at high risk (≥2 type 1 diabetes autoantibodies and dysglycemia), teplizumab slowed the progression to clinical disease. [97] Herold KC, Bundy BN. Long SA, et al. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes.N Engl J Med. 2019 Aug 15; 381 (7): 603-13.
https://www.doi.org/10.1056/NEJMoa1

6

http://www.ncbi.nlm.nih.gov/pubmed/31180194?tool=bestpractice.com
Teplizumab has been awarded breakthrough therapy status by the FDA to prevent or delay clinical type 1 diabetes in people at risk, which could speed up the approval process for this drug.

Langerhans islet transplant

Langerhans islets isolated from the donor pancreas are injected into the portal vein.The cells are seeded in the liver and produce insulin. Patients who undergo this procedure require immunosuppressive therapy after this. This procedure is effective in the beginning, but the long-term results are disappointing. Even in the best centers, less than 50% of patients do not need insulin in the first year, and only 10% within 5 years. [98] Shapiro AM, Ricordi C, Hering BJ, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med.2006 Sep 28; 355 (13): 1318-30.
https://www.nejm.org/doi/full/10.1056/NEJMoa061267

http://www.ncbi.nlm.nih.gov/pubmed/17005949?tool=bestpractice.com
[99] Ryan EA, Paty BW, Senior PA, et al. Five-year follow-up after clinical islet transplantation. Diabetes. 2005 Jul; 54 (7): 2060-9.
http://diabetes.diabetesjournals.org/content/54/7/2060.long

http://www.ncbi.nlm.nih.gov/pubmed/15983207?tool=bestpractice.com
The American Diabetes Association recommends that this procedure should only be performed in controlled trials at this stage.

Inhaled insulin

In June 2014, the FDA approved a rapid-acting inhaled insulin. It can be administered before meals and must be used in combination with long-acting insulin. It can cause bronchospasm in patients with asthma and chronic obstructive pulmonary disease, so it should not be used for these conditions. The most common side effects found during the 24-week safety and efficacy study were hypoglycemia, cough, and pharyngeal infections.Long-term safety data are not available. [100] US Food and Drug Administration. FDA approves Afrezza to treat diabetes. Jun 2014 [internet publication].
https://wayback.archive-it.org/7993/20170112222845/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm403122.htm
Moreover, such insulin is only available in fixed doses of 4 or 8 units. Therefore, dose adjustments can only be made in multiples of 4, which can present certain difficulties for accurate dose selection for patients with type 1 diabetes.More experience is needed before inhaled insulin can be prescribed as a standard treatment for type 1 diabetes.

Regeneration of islets of Langerhans

Clinical studies carried out in mouse models show that from the moment of onset of insulinitis, a formation is formed from beta cells within the focus of inflammation, which can be collected and which can serve as a future source of working beta cells. [101] Akirav E, Kushner JA, Herold KC.Beta-cell mass and type 1 diabetes: going, going, gone? Diabetes. 2008 Nov; 57 (11): 2883-8.
http://diabetes.diabetesjournals.org/content/57/11/2883.long

http://www.ncbi.nlm.nih.gov/pubmed/18971435?tool=bestpractice.com
Several clinical studies are underway to investigate mono and combination therapies to stop inflammation and possible beta cell regeneration.

Insulin sensitizers

A systematic review suggests that metformin use in children with type 1 diabetes decreases insulin requirements, but not A1C (glycosylated hemoglobin) levels one year after initiation.[102] Vella S, Buetow L, Royle P, et al. The use of metformin in type 1 diabetes: a systematic review of efficacy. Diabetologia. 2010 May; 53 (5): 809-20.
https://link.springer.com/article/10.1007%2Fs00125-009-1636-9

http://www.ncbi.nlm.nih.gov/pubmed/20057994?tool=bestpractice.com
Further clinical studies are needed to pinpoint the indications and benefits of this treatment for type 1 diabetes. [103] DeGeeter M, Williamson B. Alternative agents in type 1 diabetes in addition to insulin therapy: metformin, alpha-glucosidase inhibitors, pioglitazone, GLP-1 agonists, DPP-IV inhibitors, and SGLT-2 inhibitors.J Pharm Pract. 2016 Apr; 29 (2): 144-59.
http://www.ncbi.nlm.nih.gov/pubmed/25312263?tool=bestpractice.com
[104] Petrie JR, Chaturvedi N, Ford I, et al; REMOVAL Study Group. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomized, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017 Aug; 5 (8): 597-609.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641446/

http://www.ncbi.nlm.nih.gov/pubmed/28615149?tool=bestpractice.com

Inhibitors of the sodium-dependent glucose co-transporter 2

Inhibitors of the sodium-dependent glucose co-transporter 2 (NGKG-2) lower glucose levels in an insulin-dependent manner by suppressing NZKG-2 in the proximal renal tubule and blocking glucose reabsorption. They are associated with mild reductions in body weight and blood pressure. NZKG-2 inhibitors are approved for use in people with type 2 diabetes. The risk of normoglycemic diabetic ketoacidosis has been reported several times in both type 1 and type 2 diabetes.[105] Garg SK, Henry RR, Banks P, et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes. N Engl J Med. 2017 Dec 14; 377 (24): 2337-48.
https://www.nejm.org/doi/10.1056/NEJMoa1708337

http://www.ncbi.nlm.nih.gov/pubmed/28899222?tool=bestpractice.com
[106] Hampp C, Swain RS, Horgan C, et al. Use of sodium-glucose cotransporter 2 inhibitors in patients with type 1 diabetes and rates of diabetic ketoacidosis. Diabetes Care. 2020 Jan; 43 (1): 90-7.
https: // www.doi.org/10.2337/dc19-1481

http://www.ncbi.nlm.nih.gov/pubmed/31601640?tool=bestpractice.com
Research is ongoing to evaluate the safety and efficacy of this class of drugs in type 1 diabetes. [1] American Diabetes Association. Standards of medical care in diabetes – 2020. Diabetes Care. 2020; 43 (suppl 1): S1-212.
https://care.diabetesjournals.org/content/43/Supplement_1
[107] Chen J, Fan F, Wang JY, et al. The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis.Sci Rep. 2017 Mar 9; 7: 44128.
https://www.nature.com/articles/srep44128

http://www.ncbi.nlm.nih.gov/pubmed/28276512?tool=bestpractice.com
[108] Taylor SI, Blau JE, Rother KI, et al. SGLT2 inhibitors as adjunctive therapy for type 1 diabetes: balancing benefits and risks. Lancet Diabetes Endocrinol. 2019 Dec; 7 (12): 949-58.
https://www.doi.org/10.1016/S2213-8587(19)30154-8

http://www.ncbi.nlm.nih.gov/pubmed/31585721?tool=bestpractice.com
The European Medicines Assessment Agency for Medicinal Products for Medical Use (CHMP) has approved the use of the selective NZKG-2 inhibitor dapagliflozin for use in patients with type 1 diabetes mellitus and a BMI ≥27 kg / m 2 as an adjunct insulin agents when insulin therapy alone does not provide adequate glycemic control despite optimal insulin therapy.[109] Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicenter, double-blind, phase 3, randomized controlled trial. Lancet Diabetes Endocrinol. 2017 Sep 14; 5 (11): 864-76.
http://www.ncbi.nlm.nih.gov/pubmed/28919061?tool=bestpractice.com
[110] Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: the DEPICT-1 52-week study.Diabetes Care. 2018 Oct 23; 41 (12): 2552-9.
http://www.ncbi.nlm.nih.gov/pubmed/30352894?tool=bestpractice.com
[111] Mathieu C, Dandona P, Gillard P, et al; DEPICT-2 Investigators. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 Study): 24-week results from a randomized controlled trial. Diabetes Care. 2018 Jul 19; 41 (9): 1938-46.
http://care.diabetesjournals.org/content/41/9/1938.long

http://www.ncbi.nlm.nih.gov/pubmed/30026335?tool=bestpractice.com
In March 2019, KMLP also recommended approval of sotagliflozin, a dual inhibitor of NGR-1 and NGR-2, for the same indication [105] Garg SK, Henry RR, Banks P, et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes. N Engl J Med. 2017 Dec 14; 377 (24): 2337-48.
https://www.nejm.org/doi/10.1056/NEJMoa1708337

http://www.ncbi.nlm.nih.gov/pubmed/28899222?tool=bestpractice.com
[112] Danne T, Cariou B, Buse JB, et al. Improved time in range and glycemic variability with sotagliflozin in combination with insulin in adults with type 1 diabetes: a pooled analysis of 24-week continuous glucose monitoring data from the inTandem Program.Diabetes Care. 2019 May; 42 (5): 919-30.
http://www.ncbi.nlm.nih.gov/pubmed/30833371?tool=bestpractice.com
[113] Buse JB, Garg SK, Rosenstock J, et al. Sotagliflozin in combination with optimized insulin therapy in adults with type 1 diabetes: the North American inTandem1 Study. Diabetes Care. 2018 Jun 24; 41 (9): 1970-80.
http://care.diabetesjournals.org/content/41/9/1970.long

http://www.ncbi.nlm.nih.gov/pubmed/29937430?tool=bestpractice.com
[114] Danne T, Cariou B, Banks P, et al.HbA1c and hypoglycemia reductions at 24 and 52 weeks with sotagliflozin in combination with insulin in adults with type 1 diabetes: the European inTandem2 Study. Diabetes Care. 2018 Jun 24; 41 (9): 1981-90.
http://care.diabetesjournals.org/content/41/9/1981.long

http://www.ncbi.nlm.nih.gov/pubmed/29937431?tool=bestpractice.com
[115] Musso G, Gambino R, Cassader M, et al. Efficacy and safety of dual SGLT 1/2 inhibitor sotagliflozin in type 1 diabetes: meta-analysis of randomized controlled trials.BMJ. 2019 Apr 9; 365: l1328.
https://www.doi.org/10.1136/bmj.l1328

http://www.ncbi.nlm.nih.gov/pubmed/30967375?tool=bestpractice.com
However, in March 2019, the UPM rejected approval for the use of sotagliflozin for the treatment of type 1 diabetes. Patients should be adhered to to minimize the increased risk of developing diabetic ketoacidosis with both drugs.

Glucagon-like peptide-1 (GLP-1) agonists

GLP-1 is an intestinal peptide that increases insulin secretion and decreases glucagon secretion in a glucose-dependent manner.In patients with type 2 diabetes, GLP-1 receptor agonists increase GLP-1 levels and increase glucose-dependent insulin secretion, decrease glucagon secretion, delay gastric emptying and increase satiety. A specific advantage of GLP-1 receptor agonists is weight reduction, which is desirable for most patients with type 1 diabetes. [116] Janzen KM, Steuber TD, Nisly SA. GLP-1 agonists in type 1 diabetes mellitus. Ann Pharmacother. 2016 Aug; 50 (8): 656-65.http://www.ncbi.nlm.nih.gov/pubmed/27252246?tool=bestpractice.com
The addition of a GLP receptor agonist to insulin therapy improves glucose control in clinical trials of type 1 diabetes, but also leads to an increased risk of both hypoglycemia and hyperglycemia with ketosis. Thus, GLP-1 receptor agonists should not be routinely used in type 1 diabetes.

Experience that matters. VII All-Russian Congress of Endocrinologists. AstraZeneca Satellite Symposium

As part of the VII All-Russian Congress of Endocrinologists, a satellite symposium of AstraZeneca was held, where leading Russian and foreign experts discussed approaches to the treatment of patients with type 2 diabetes mellitus and considered the therapeutic possibilities of a wide range of antihyperglycemic drugs.Source: Umedp.ru.

Can Integrated Solutions Change Current Clinical Practice?

Professor, Head of the Department of Endocrinology and Diabetology of the Russian Medical Academy of Postgraduate Education, Honored Scientist of the Russian Federation, Doctor of Medical Sciences Alexander Sergeevich AMETOV at the beginning of his speech noted that the prevalence of diabetes mellitus (DM) continues to increase, which means that an increasing number of patients require special attention and active drug treatment.In addition, diagnosis is often delayed and many diagnosed patients do not achieve treatment goals and therefore cannot manage their disease. As a result, the risk of developing cardiovascular disease and premature death increases. The presence of vascular complications, in turn, significantly reduces the quality of life of patients.

Treatment of diabetes mellitus is a difficult task, since all organs and tissues are somehow involved in the pathological process. Hyperglycemia is the primary underlying cause of many disorders in diabetic patients.

Currently, there are eight reasons for the development of hyperglycemia – a threatening octet. First of all, this is a dysfunction of the beta cells of the pancreas in relation to the secretion of insulin, which is necessary to overcome insulin resistance. In parallel with the dysfunction of beta cells, there is a decrease in the mass of functioning cells. This can be the cause of the development of fasting hyperglycemia and postprandial glycemia. Further, if we talk about the pancreas, the islet apparatus, alpha-cell dysfunction, which leads to an increase in glucagon secretion.As a result, increased gluconeogenesis and fasting glycemia. In addition, there is a decrease in the insulin sensitivity of the target tissues. Insulin resistance of liver cells is manifested by insufficient suppression of gluconeogenesis, as a result of which fasting glucose levels increase, as well as impaired glycogen synthesis and an increase in glucose levels after meals. Muscle tissue also plays an important role in the regulation of glucose homeostasis. Thus, the development of insulin resistance and a decrease in glucose utilization lead to an increase in fasting glucose and after a meal.

In recent years, the study of the role of hormones of the gastrointestinal tract (GIT) in the regulation of insulin secretion, and, consequently, in the regulation of glucose homeostasis in the body, has been of great scientific and practical interest. The important role of hormones such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) has been proven. A decrease in signals from GLP-1 / GIP, information exchange between various organs and tissues, production of GLP-1 / GIP, although this is quite rare, as well as the resistance of beta cells to GLP-1 / GIP, lead to a decrease postprandial insulin secretion and postprandial glycemia.

Clinical observations of recent years indicate the existence of a causal relationship between the dysregulation of glucose homeostasis and the work of the central nervous system, in particular, the development of insulin resistance in the brain due to neurotransmitter dysfunction.

And one more of the central organs that ensure the balance of glucose in the body is the kidneys. Increased renal reabsorption of glucose leads to hyperfiltration.

The kidneys perform a number of important functions, such as filtration, secretion, and reabsorption.The kidneys perform endocrine and metabolic functions, producing physiologically active substances. Basic kidney function is considered critical in the regulation of fluid and electrolyte balance, osmolarity of body fluids, acid balance, excretion of metabolic wastes and foreign molecules.

The kidneys are involved in the regulation of blood pressure (BP), hormone secretion and glucose balance. They, like the beta cell, being an “energy sensor”, control the concentration of circulating nutrients (with the participation of neurohormonal signals) and ensure the balance of glucose in the body.

Professor A.S. Ametov noted that the optimal treatment of type 2 diabetes involves work in two directions – the management of hyperglycemia and dysmetabolic syndrome. “The time has come to expand and redefine the concept of intensive care,” the speaker emphasized. The goal of intensive care for diabetes should be to reduce the risk of developing and progression of complications through the implementation of measures aimed at reducing vascular risk on a regular and long-term basis.

In the analysis of a number of studies (ACCORD, ADVANCE, VADT, UKPDS, etc.) devoted to the study of glycemic control parameters, the importance of glycated hemoglobin (HbA1c) control for reducing the risk of complications in patients with type 4 diabetes was demonstrated. However, the need to limit tight glycemic control with existing pharmaceuticals has been shown. This is due to the fact that the standard approach to assessing the effectiveness of diabetes treatment by the level of HbA1c assumes control of the average level of glycemia, but does not take into account its fluctuations.

It is necessary to treat the disease itself, not its symptom, that is, hyperglycemia. “It is important to understand that we are treating the disease, not just lowering glucose, we are treating the patient, not his glycemic level. Glucose is energy, without which no process in the body takes place, the speaker emphasized. – This is one of the main energy substrates. There is a so-called systemic demand for energy in the body, as well as a system that distributes this demand. ”

In connection with the change in ideas about the mechanisms of development of type 2 diabetes and the development of the concept of “threatening octet”, it is necessary to change the principles of treatment.

Management of type 2 diabetes today requires the use of drug combinations to correct various pathophysiological defects. To prevent beta cell dysfunction, therapy should be started as early as possible.

Currently, for the treatment of type 2 diabetes, there are several classes of hypoglycemic drugs with different mechanisms of action: sulfonylurea derivatives, metformin, thiazolidinediones, dipeptidyl peptidase 4 (DPP-4) inhibitors, GLP-1 agonists and inhibitors of the sodium glucose cotransporter type 2 ( 2).

SGLT-2 inhibitors – a new class of antidiabetic drugs that affect glycemic regulation regardless of insulin secretion and the patient’s glycemic status. A feature of this class of drugs is their effect on reducing body weight, blood pressure and, importantly, the minimum risk of hypoglycemia6. The active and highly selective inhibitor of SGLT-2 reversible action dapagliflozin (Forsiga®, AstraZeneca) improves the control of type 2 diabetes.

Five independent observational studies evaluated the reduction in HbA1c and body weight in standard practice in the UK primary care stage in patients with type 2 diabetes who were prescribed dapagliflozin8-12.Data analysis confirmed the effectiveness of dapagliflozin therapy in real clinical practice. There was a decrease in HbA1c levels and body weight during dapagliflozin therapy with different treatment regimens: double combination (added to metformin), triple and added to insulin.

Further, Professor A.S. Ametov reviewed a clinical case.

Patient 58 years old. The disease was diagnosed eight years ago. Sugar-lowering therapy included metformin 250 mg / day and modified-release gliclazide 90 mg / day.The patient has distal diabetic polyneuropathy, ischemic heart disease, stage II arterial hypertension, in 2013 – pulmonary embolism. Body mass index – 35.2 kg / m2. The HbA1c level is 8.6%.

Then the patient received intensive therapy: sitagliptin and metformin in a fixed combination 50/100 mg twice a day, modified release gliclazide 90 mg / day, prolonged-release metformin 500 mg at night. The drug Forsiga® 10 mg was added to the complex of hypoglycemic therapy.Already on the sixth day of taking the drug, the patient’s HbA1c level returned to normal.

Thus, the SGLT-2 inhibitor (dapagliflozin) has become the optimal drug for intensifying therapy in this patient. Additional advantages of its use are a moderate decrease in blood pressure and a low risk of hypoglycemia.

Concluding his speech, Professor A.S. Ametov noted that the SGLT-2 inhibitor (Forsiga®) is indicated for patients with type 2 diabetes at all stages of therapy to improve glycemic control.It can be used both as monotherapy and in combination therapy with other hypoglycemic drugs6.

Dapagliflozin – a place in real clinical practice. What is the ideal patient like?

Professor Andrea GIACCARI (President of the Association for the Study of Diabetes, Department of Endocrine and Metabolic Diseases, A. Gemelli University, Rome, Italy) in his speech focused on the choice of optimal therapy to achieve glycemic control in patients with type 2 diabetes.The speaker stated that today there is a large selection of antihyperglycemic drugs on the pharmaceutical market. In this regard, clinicians are faced with a serious task – to choose the most effective and safe treatment regimen for the patient.
To select a therapy, it is necessary to take into account the patient’s body weight, age, comorbidities, complications, diet, physical activity, compliance, nature of work, glycemic phenotype and pathogenesis of hyperglycemia, as well as clinical phenotype.

Today, metformin remains one of the most widely used antidiabetic drugs. It is recommended as a starting therapy for type 2 diabetes. This is due to the fact that metformin is the only drug with proven efficacy in the primary prevention of cardiovascular disease in patients with type 2 diabetes. The mechanism of the antihyperglycemic action of metformin is well understood.

What and how can be combined with metformin? How to choose the right option?

There are currently six classes of drugs for the treatment of diabetes that can be used in combination with metformin: sulfonylurea derivatives, acarbose, pioglitazone, incretins (DPP-4 inhibitors and GLP-1 agonists), SGLT-2 inhibitors, and insulin.With six drug classes, 720 combinations with metformin can be made. How to choose the right combination? Based on personal experience or the effectiveness of therapy? However, the effectiveness of the same therapy may differ in different patients …

The optimal choice should be based on the pros and cons of each treatment option, that is, evidence-based medicine.

The speaker reviewed several classes of antihyperglycemic drugs in terms of the evidence base.Sulfonylurea derivatives and repaglinide are fast acting and economically available. The arguments against their use in combination with metformin are the high incidence of hypoglycemia, rapid depletion of beta cells, weight gain and increased cardiovascular risk. A contraindication to the use of sulfonylurea derivatives and repaglinide is chronic kidney disease. Some sources indicate a certain risk of developing myocardial infarction against the background of their use.

The advantages of GLP-1 agonists include the absence of the risk of hypoglycemia, a significant decrease in body weight and cardiovascular risk, and easy dose titration.However, among their disadvantages are side effects from the gastrointestinal tract, the need for injections and the high cost. Drugs in this class are not indicated for chronic renal failure.

The advantages of drugs of the class of DPP-4 inhibitors, or gliptins, are considered the absence of the risk of hypoglycemia, stimulation of insulin secretion / suppression of glucagon secretion, rare side effects, no effect on cardiovascular risk factors, side effects from the gastrointestinal tract and the need for dose titration.The only argument against is the high cost of the drugs. There was evidence of a small risk of developing heart failure with the use of DPP-4 inhibitors, but they are contradictory.

A new class of antidiabetic drugs, SGLT-2 inhibitors, or glyflozins, is of great interest in the medical community. In patients with type 2 diabetes, an increased renal reabsorption of glucose makes a significant contribution to the maintenance of hyperglycemia. SGLT-2 inhibitors reduce the concentration of glucose in the blood by stimulating its excretion in the urine.Moreover, the effect of SGLT-2 inhibitors does not depend on the degree of insulin resistance and beta-cell deficiency.

The glucose-lowering efficacy of combination therapy with an SGLT-2 inhibitor (dapagliflozin 10 mg) and metformin was comparable to that of a combination of a sulfonylurea derivative, glipizide and metformin. During treatment with an SGLT-2 inhibitor in combination with metformin, HbA1c control remained longer.

The use of dapagliflozin in combination with insulin improved glycemic control, stabilized the insulin dose and contributed to a decrease in body weight and blood pressure in patients without increasing the frequency of hypoglycemic episodes.

Numerous studies confirm that SGLT-2 inhibitors can be used to treat patients with type 2 diabetes either alone or in combination with metformin, gliptins, pioglitazone, insulin and other drug classes. The absence of hypoglycemia and an insulin-independent mechanism of action make dapagliflozin (Forsiga®) a reasonable addition to existing treatment options.

Analysis of the results of observations in real clinical practice and randomized clinical trials allows us to conclude that dapagliflozin provides a comparable decrease in the level of HbA1c, blood pressure and body weight.So, according to real clinical practice, when dapagliflozin is added to metformin and insulin, the HbA1c level decreases by an average of 0.80-1.16% (versus -0.84-0.96% in clinical trials), body weight – by 2 , 5-4.6 kg (versus -2.65 kg (metformin) and -1.6 kg (insulin)), systolic blood pressure – by 2.3 mm Hg. Art. (versus -5.1 mmHg (metformin) and -6.7 mmHg (insulin)).

Thus, SGLT-2 inhibitors in complex antihyperglycemic therapy have shown efficacy in all groups of patients, no risk of hypoglycemia, elimination of glucose toxicity, significant and persistent decrease in body weight and blood pressure.Of the negative effects of the glyflozin group, it is worth noting a slight increase in the risk of developing urogenital infections and a decrease in efficiency at a low level of the estimated glomerular filtration rate.

Professor A. Giackari presented research data confirming the efficacy of a combination of SGLT-2 and DPP-4 inhibitors in patients with type 2 diabetes. Drugs of these classes have comparable glucose-lowering efficacy and complement each other’s action due to the effect on different links of pathogenesis.A direct comparative study was carried out in which patients with type 2 diabetes, not compensated for with metformin monotherapy, were additionally prescribed dapagliflozin, saxagliptin, or their combination. At the 24th week of use in the saxagliptin and metformin group, 18% of patients achieved HbA1c <7%, in the dapagliflozin and metformin group - 22%, in the triple combination “saxagliptin + dapagliflozin + metformin” group, this figure was 41%.

Thus, the advantage of a three-way combination has been demonstrated to achieve glycemic control in patients with type 2 diabetes.

In conclusion, Professor A. Giackari emphasized that there can be no single decision when choosing a therapy for type 2 diabetes, the treatment must be individual. The advantages and disadvantages of each drug for a particular patient must be carefully weighed.

Incremental therapy: confidence based on years of experience

Professor of the Department of Endocrinology and Diabetology of the Russian Medical Academy of Postgraduate Education of the Ministry of Health of Russia, Dr.M.Sc. Tatiana Yulievna DEMIDOVA. In clinical practice, two main classes of these drugs are used: DPP-4 inhibitors and GLP-1 agonists.

To date, DPP-4 inhibitors are a serious competitor to sulfonylureas, since they have established themselves as effective antihyperglycemic drugs with a proven safety profile both in terms of the risk of cardiovascular events and in terms of the risk of developing pancreatitis and pancreatic cancer. Saxagliptin (Onglisa drug) continues to be one of the most studied representatives of the DPP-4 inhibitor class, and its use in combination with metformin is one of the most common.

Indeed, in a head-to-head comparative study, saxagliptin has shown comparable antihyperglycemic efficacy with a sulfonylurea drug over two years of therapy in patients with type 2 diabetes. At the same time, those who received saxagliptin and metformin did not require dose titration of the drug. At the same time, those taking the drug sulfonylureas (in this case, glipizide) and metformin required dose titration on average twice, a third of patients even more than twice. A similar decrease in HbA1c levels in both groups persisted for two years (104 weeks).It should be noted that with the equal glucose-lowering efficacy of saxagliptin and sulfonylurea, the frequency of hypoglycemia noted in the saxagliptin and metformin group was 10 times less than in the comparison group – 3 versus 36.3% of cases.

Analysis of the results of a three-year (154 weeks) follow-up evaluating the effectiveness of combination therapy with saxagliptin and metformin in patients with type 2 diabetes showed that this therapy regimen provides longer, clinically significant glycemic control compared to metformin monotherapy.This does not increase the risk of developing episodes of hypoglycemia and weight gain.

The effectiveness of the drug plays an important role in deciding on the initiation of antihyperglycemic therapy. It was found that when using the starting combination “Saxagliptin 5 mg + Metformin”, the dynamics of HbA1c indicators depended on the initial level of glycemia. So, after 24 weeks of treatment, all patients who received saxagliptin in combination with metformin showed a significant decrease in the HbA1c level from the baseline, and the higher the initial level, the more significant the decrease was.It should be noted that in this study, in patients with type 2 diabetes with a baseline HbA1c level above 10%, administration of saxagliptin together with metformin led to a 3.3% decrease in this indicator.

Currently, one of the most important criteria when choosing a therapy is safety, including the lack of influence on the risk of developing cardiovascular complications. SAVOR-TIMI 53, a large-scale multicenter prospective phase IV study of 16,492 patients, evaluated the cardiovascular safety of saxagliptin29.The advantage of the study was that it included patients with different baseline characteristics. Therefore, the results obtained can be more reliably extrapolated to the entire cohort of patients with type 2 diabetes in everyday clinical practice.

The use of saxagliptin in patients with type 2 diabetes with cardiovascular diseases or multiple cardiovascular risk factors was not accompanied by an increase in the incidence of nonfatal myocardial infarction and ischemic stroke, as well as cardiovascular death, compared with patients taking placebo.The study found an increase in hospital admissions for chronic heart failure in the saxagliptin group compared with the placebo group (3.5% and 2.8%, respectively). However, the difference between the groups was small, and among those hospitalized for it, there was no increase in the frequency of deaths. In the SAVOR study, levels of the N-terminal fragment of brain natriuretic peptide (NT-proBNP) did not differ between the saxagliptin and placebo groups. NT-proBNP levels provide an objective assessment of cardiovascular risk in patients with chronic heart failure and predict a poor prognosis.

In addition, it has been proven that saxagliptin is one of the safest antidiabetic drugs for the treatment of older patients. The use of saxagliptin in elderly patients did not increase the risk of developing acute myocardial infarction, stroke. Against the background of such therapy, an increase in the incidence of cardiovascular death was not recorded. The risk of hospitalization due to chronic heart failure did not depend on the age of the patients.

According to the speaker, the preferred treatment for type 2 diabetes is a fixed combination of modified release metformin (MV) and saxagliptin (Combogliz Prolong®, AstraZeneca).

The drug Combogliz Prolong® combines two hypoglycemic drugs with complementary mechanisms of action. The peculiarity of the dosage form of metformin MB is the structure of the hydrophilic matrix system of the tablet. Once in the gastrointestinal tract, the matrix system is hydrated under the influence of gastric juice with the formation of a gel, which, combined with physiological slowdown of gastrointestinal tract motility at night, ensures uniform absorption of metformin hydrochloride in the upper gastrointestinal tract32. This allows you to take the drug once a day, after dinner, and, as a result, can improve adherence to therapy.Better tolerance of this form compared to the usual form of metformin was recorded: a decrease in the frequency of adverse events from the gastrointestinal tract by 50%, the risk of diarrhea by 75%.

The drug Combogliz Prolong® effectively controls glycemia, is characterized by cardiovascular safety, a low risk of hypoglycemia, and no effect on body weight.

Further T.Yu. Demidova focused on the therapeutic efficacy of GLP-1 agonists. The professor noted that 10 years ago, the first analogue of GLP-1 exenatide was registered in our country (Byeta®, AstraZeneca).Over the years, a positive experience of its use in diabetological practice has been accumulated. In numerous studies, Exenatide has shown clinically significant, dose-dependent, long-term improvement in key parameters of glycemic control with a low risk of hypoglycemia.

The choice of a method for further intensification of treatment in patients with type 2 diabetes, already receiving insulin, but not achieving satisfactory glycemic control against its background, is the area of ​​special responsibility of each specialist.Therapy in such patients is complicated by the increasing risk of hypoglycemia due to an increase in the insulin dose, an increase in body weight, the need to provide an adequate dose of insulin and other hypoglycemic agents in the case of combined use. Therefore, to date, a combination of a GLP-1 agonist (Byeta) and basal insulin is proposed to intensify insulin therapy6. In an open-label, multicenter, randomized trial, it was shown that the hypoglycemic effect of Exenatide when used with basal insulin (glargine) is comparable to that of insulin lispro.The dynamics of the HbA1c level was also comparable. Exenatide reduces HbA1c levels by acting on postprandial hyperglycemia. Against the background of therapy, including the drug Byetta®, in patients with type 2 diabetes, a more pronounced decrease in fasting glycemia was observed. In addition, the use of Exenatide in combination with glargine resulted in a statistically significant decrease in body weight (-2.5 kg) compared with the use of lispro and glargine.

Therefore, the addition of a short-acting GLP-1 agonist instead of ultrashort insulin before meals represents a novel therapeutic strategy for patients in whom intensification of basal insulin treatment does not lead to optimal glycemic control.

Summing up, Professor T.Yu. Demidova noted that the pronounced hypoglycemic effect is the key line of the strategy for approaching treatment and reducing vascular risks in patients with type 2 diabetes. Therefore, incretin therapy is a good alternative to traditional therapeutic strategies.

Conclusion

Today, when choosing a therapy for patients with type 2 diabetes, not only the hypoglycemic efficacy of drugs is considered, but also their cardiovascular safety, the risk of hypoglycemia and weight gain.In recent years, new classes of antihyperglycemic drugs have been developed and introduced into clinical practice, such as DPP-4 inhibitors, GLP-1 agonists and SGLT-2 inhibitors.

Combogliz Prolong® (AstraZeneca) combines two hypoglycemic drugs – the DPP-4 inhibitor saxagliptin and metformin. They have complementary mechanisms of action. The components of Combogliz Prolong® demonstrate effective glycemic control and cardiovascular safety, good tolerance, a low risk of hypoglycemia and a neutral effect on body weight.The fixed combination improves patient adherence to treatment. As shown by the research results, fixed combination therapy with Combogliz Prolong® can be recommended for elderly patients due to its good efficacy and tolerance.

Forsiga® (AstraZeneca) is a modern antihyperglycemic agent containing dapagliflozin. Dapagliflozin is an active and highly selective inhibitor of SGLT-2 with a reversible effect.The main hypoglycemic effect of dapagliflozin does not depend on insulin secretion and its activity. Dapagliflozin has a high bioavailability when administered orally, is rapidly absorbed from the gastrointestinal tract.

In numerous studies, Forsiga®, both as a monotherapy and as a combination therapy, has demonstrated an effective reduction in glycemia with a low risk of hypoglycemia. Additional benefits of the drug are a decrease in body weight and blood pressure without a compensatory increase in heart rate.The regimen of drug administration – once a day, regardless of food intake at any convenient time – contributes to an increase in patients’ adherence to treatment.

Byeta® (Exenatide) is a hypoglycemic drug for subcutaneous administration. It is a GLP-1 receptor stimulant. Byeta® mimics the effect of the natural human incretin hormone, GLP-1, released during meals. The unique properties of this drug are glucose-dependent stimulation of insulin secretion, suppression of the release of glucagon after eating, slowing down the speed and reducing food intake, which leads to a decrease in body weight.The use of Byetta® leads to the normalization of carbohydrate metabolism. During therapy, there is a decrease in body weight and a low risk of hypoglycemia. The clinical efficacy of Byeta has been proven in a number of long-term studies.

Source: Umedp.ru

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