How does the combination of Glimepiride and Metformin work to control blood sugar levels. What are the potential side effects and drug interactions of this diabetes medication. How should patients take Glimepiride and Metformin for optimal results.

Understanding Glimepiride and Metformin: A Powerful Duo for Diabetes Management

Glimepiride and Metformin are two medications commonly prescribed together to help manage type 2 diabetes. This powerful combination works synergistically to control blood sugar levels through different mechanisms of action. Let’s explore how these drugs function individually and in tandem to improve glycemic control in diabetic patients.

How Does Glimepiride Work?

Glimepiride belongs to a class of drugs called sulfonylureas. Its primary function is to stimulate the pancreas to produce and release more insulin. By enhancing insulin secretion, Glimepiride helps lower blood sugar levels in the following ways:

• Increases insulin production by pancreatic beta cells
• Improves insulin sensitivity in peripheral tissues
• Enhances glucose uptake by cells
• Reduces glucose output from the liver

How Does Metformin Work?

Metformin, on the other hand, is a biguanide that primarily targets insulin resistance. It works through several mechanisms to lower blood glucose:

• Decreases glucose production in the liver
• Improves insulin sensitivity in muscle and fat cells
• Reduces glucose absorption in the intestines
• Increases glucose uptake and utilization in peripheral tissues

By combining these two medications, doctors can address multiple aspects of blood sugar control, making it an effective strategy for managing type 2 diabetes.

Benefits of Combining Glimepiride and Metformin for Diabetes Treatment

The combination of Glimepiride and Metformin offers several advantages for patients with type 2 diabetes. These benefits include:

1. Complementary mechanisms of action
2. Improved glycemic control
3. Potential for lower doses of each medication
4. Reduced risk of side effects compared to higher doses of individual drugs
5. Convenience of taking fewer pills

Are there any specific patient populations that benefit most from this combination therapy? While individual cases may vary, the Glimepiride-Metformin combination is often particularly effective for patients who have not achieved adequate blood sugar control with metformin alone or those who require multiple medications to manage their diabetes.

Proper Dosage and Administration of Glimepiride and Metformin

Determining the right dosage of Glimepiride and Metformin is crucial for optimal diabetes management. Healthcare providers typically start with lower doses and adjust based on the patient’s response and blood sugar levels. Here are some key points to consider:

• Initial dosing is usually once or twice daily with meals
• Dosage may be increased gradually to achieve target blood glucose levels
• Maximum daily doses: Glimepiride (8 mg) and Metformin (2000 mg)
• Doses may be adjusted based on kidney function and other individual factors

Should patients take Glimepiride and Metformin together or separately? In many cases, these medications are available as a combination pill for convenience. However, some patients may be prescribed separate tablets to allow for more flexible dosing. Always follow your healthcare provider’s instructions regarding timing and administration.

Potential Side Effects and Risks of Glimepiride and Metformin Therapy

While Glimepiride and Metformin are generally well-tolerated, patients should be aware of potential side effects. Common side effects may include:

• Nausea and vomiting
• Diarrhea or stomach discomfort
• Headache
• Dizziness
• Hypoglycemia (low blood sugar)

More serious but rare side effects can occur, such as lactic acidosis with Metformin or severe hypoglycemia with Glimepiride. Patients should be vigilant and report any unusual symptoms to their healthcare provider promptly.

Can the risk of side effects be minimized? Yes, several strategies can help reduce the likelihood of experiencing adverse effects:

1. Starting with low doses and titrating slowly
2. Taking medications with food to reduce gastrointestinal side effects
3. Monitoring blood glucose levels regularly
4. Staying well-hydrated
5. Avoiding excessive alcohol consumption

Drug Interactions and Precautions for Glimepiride and Metformin Use

Understanding potential drug interactions is crucial for patients taking Glimepiride and Metformin. These medications can interact with various substances, including:

• Other diabetes medications
• Certain antibiotics
• Some blood pressure medications
• Diuretics
• Corticosteroids
• Alcohol

Why is it important to inform healthcare providers about all medications and supplements? By providing a complete list of all drugs and supplements you’re taking, your doctor can assess potential interactions and adjust your treatment plan accordingly. This helps prevent adverse effects and ensures the effectiveness of your diabetes management.

Special Precautions for Certain Patient Groups

Some patients may require extra caution when using Glimepiride and Metformin:

• Elderly patients (increased risk of hypoglycemia)
• Those with kidney or liver impairment
• Patients undergoing surgery or medical procedures
• Pregnant or breastfeeding women

In these cases, close monitoring and potential dose adjustments may be necessary to ensure safe and effective treatment.

Lifestyle Modifications to Enhance the Effectiveness of Glimepiride and Metformin

While Glimepiride and Metformin are powerful tools for managing diabetes, they work best when combined with healthy lifestyle choices. Patients can optimize their treatment by incorporating the following strategies:

1. Following a balanced, diabetes-friendly diet
2. Engaging in regular physical activity
3. Maintaining a healthy weight
4. Monitoring blood glucose levels as recommended
5. Managing stress through relaxation techniques
6. Getting adequate sleep

How do these lifestyle modifications complement medication therapy? By adopting these healthy habits, patients can improve insulin sensitivity, reduce the body’s glucose production, and enhance the effectiveness of their medications. This holistic approach often leads to better glycemic control and may even allow for lower medication doses over time.

Monitoring and Follow-up Care for Patients on Glimepiride and Metformin

Regular monitoring is essential for patients taking Glimepiride and Metformin to ensure optimal diabetes management and detect any potential issues early. Key aspects of follow-up care include:

• Regular blood glucose monitoring (both fasting and postprandial)
• Periodic HbA1c tests to assess long-term glucose control
• Kidney function tests
• Liver function tests
• Regular check-ups with healthcare providers

Why is consistent monitoring crucial for patients on this combination therapy? Regular check-ups and tests allow healthcare providers to assess the effectiveness of the treatment, make necessary adjustments, and catch any potential complications early. This proactive approach helps ensure the best possible outcomes for patients managing their diabetes with Glimepiride and Metformin.

Patient Education and Self-Management

Empowering patients with knowledge and skills is a crucial component of successful diabetes management. Key areas of focus include:

• Understanding how to recognize and manage hypoglycemia
• Proper use of blood glucose monitoring devices
• Medication adherence strategies
• Nutrition and meal planning
• Incorporating physical activity safely
• Foot care and other preventive measures

By actively participating in their care and staying informed, patients can maximize the benefits of their Glimepiride and Metformin therapy while minimizing risks.

Alternatives and Complementary Treatments to Glimepiride and Metformin

While Glimepiride and Metformin are effective for many patients, alternative or additional treatments may be considered in certain situations. These may include:

1. Other oral diabetes medications (e.g., DPP-4 inhibitors, SGLT2 inhibitors)
2. Injectable medications (e.g., GLP-1 receptor agonists, insulin)
3. Herbal supplements (under medical supervision)
4. Bariatric surgery for severe obesity

When might a healthcare provider consider alternative treatments? Alternatives may be explored if a patient experiences significant side effects, fails to achieve adequate glucose control, or has contraindications to Glimepiride or Metformin. The decision to change or add treatments should always be made in consultation with a healthcare professional.

Emerging Therapies and Research

The field of diabetes management is constantly evolving, with new treatments and technologies on the horizon. Some areas of ongoing research include:

• Novel drug combinations
• Artificial pancreas systems
• Stem cell therapies
• Gene editing approaches

While these innovations hold promise, it’s important for patients to focus on currently approved and evidence-based treatments while staying informed about potential future options.

In conclusion, the combination of Glimepiride and Metformin offers a powerful approach to managing type 2 diabetes. By understanding how these medications work, following proper dosing guidelines, being aware of potential side effects and interactions, and adopting healthy lifestyle habits, patients can optimize their diabetes management and improve their overall health outcomes. Regular monitoring and open communication with healthcare providers are key to successful long-term diabetes control with this medication combination.

Glimepiride and Metformin Tablet Uses, Side Effects, Dosage & Interaction

Last updated on April 9th, 2022

Glimepiride and Metformin, both help diabetes patients in keeping their blood sugar levels under control. Being an anti-diabetic drug, Metformin chemically biguanide, helps reduce glucose production within the liver, while Glimepiride lowers blood sugar by enhancing the release of body’s natural insulin (a natural substance that is needed to break down sugar in the body) and helps the body use insulin efficiently. It belongs to a class of drugs called sulfonylureas.

Doctors administer these medications together to maintain optimal blood glucose levels in the patient’s body.

Table of Contents

Uses of Glimepiride and Metformin

Glimepiride helps in combating type 2 diabetes. This drug will only help lower blood sugar in people whose bodies naturally produce insulin and is ineffective in diabetes mellitus type 1.  Doctors recommend having these medicines along with a healthy diet and adequate exercising.

This medicine can be used with insulin or other types of diabetes medicines to help control your high blood sugar.

Metformin reacts in your body to bring down the blood sugar levels. Doctors suggest having this drug along with a healthy diet and sufficient exercise. When a patient takes metformin, it helps restore the insulin response that occurs naturally in the human body. Taking this drug as per the doctor’s recommendation, aids in reducing sugar production by the liver.

In most of the cases of type 2 diabetes, the doctor suggests consuming Glimepiride and Metformin in a combination form after analysing the patient’s condition. In this case, you must:

• Follow the instructions given by the doctor
• Take medications as mentioned in the prescription
• Read the info available on the medicine cover carefully
• Understand the procedure perfectly
• Doctors usually prescribe two doses of each medicine for a day, but depending upon your condition, your dosage might be adjusted

Summary

Glimepiride and Metformin are known to produce great results for diabetes, and are the best combinational anti-diabetic drugs available in the market. However, since diabetes is a lifestyle disorder, for better results, the drugs must be taken along with a healthy diet and sufficient amount of exercise.

Side Effects of Glimepiride and Metformin

This medicine can cause changes in blood sugar levels. You need to know the symptoms of low and high blood sugar and what to do if you have these symptoms.
Glimepiride and Metformin, when taken in combination, may cause some side effects. Consult with your physician as soon as possible if any of the below-mentioned symptoms get severe or persist for a significant amount of time
Side effects Glimepiride and Metformin could be: 

• Nausea
• Dizziness
• Vomiting
• Headache
• Hypoglycemia
• Deep or rapid breathing
• Muscle spasms
• Upper respiratory tract infection
• Taste change
• Stomach Ache
• Loss of energy
• Fatigue
• Restlessness
• Muscle weakness
• seizures
• Loss of appetite
• Irritability
• Muscle cramps
• Confusion

It is advised to immediately see your doctor if you suffer from any of the above-mentioned health issues. After evaluating your condition, your doctor will determine the future course of action to help you in getting relief from the side effects.

It is a rare occurrence, but sometimes, the patient may suffer from severe side-effects, such as lactic acidosis (which is an excess of lactic acid in the blood) or yellowing of the eyes or skin (jaundice). In such cases, the patients are advised to immediately see a doctor to cut down the chances of anything serious.

Also, you must tell your doctor if you have a history of being allergic to any of the ingredients used in Glimepiride and Metformin.

Summary:

These medications, on being given together, do not usually produce any side effects, but in some patients, they may suffer from some mild symptoms like Vomiting, Headache, Hypoglycemia, Deep or rapid breathing, Muscle spasms, Upper respiratory tract infection, Taste change, Stomach Ache, etc. There are some serious side-effects also but they occur very rarely. If you experience any of these symptoms, or the symptoms persist for a long time, you are advised to see a doctor immediately.

Glimepiride Interactions

While taking glimepiride, you must talk to your doctor before consuming alcohol, as it may cause side-effects. Depending upon your condition, your doctor may suggest you to either take alcohol in moderation or stop consuming it completely.

Ignoring the warning on alcohol consumption may cause symptoms like vomiting, flushing, nausea, chest pain, headache, blurred vision, weakness, sweating, choking, breathing difficulty, mental confusion, and anxiety.

Apart from alcohol consumption, the patients while being on glimepiride are advised to avoid prolonged sun exposure. They should wear protective clothing, sunglasses and sunscreen as the medicine makes your skin sensitive to sunlight.

You should also discuss with your doctor beforehand to know the procedure to follow if you fall sick, get an infection or fever or feel stressed. These conditions may increase your blood glucose levels, leading your doctor to adjust your dosage.

Also Read: Galvus met for diabetes

Metformin Interactions

While being on metformin, you can consume alcohol but only in moderate amounts. Women can have a drink a day and men can have a couple of drinks a day while being on this medication, but drinking heavily during the time may cause serious concerns.

Heavy drinking is known to increase the risk of lactic acidosis, and it is also a side-effect of metformin. Hence, consuming both the things at the same time only doubles your chances of developing lactic acidosis.

Experts, however, clear you to eat anything while being on this drug. Metformin generally works by reducing your blood sugar levels between meals, hence, it allows you to eat anything (however, in moderation) while being on this medication.

Generally, you are advised to take metformin along with meals as it may reduce the chances of any gastrointestinal (GI) issues. You can also take metformin without food too if you do not have any symptoms of GI.

Summary

Glimepiride and Metformin, both, are very helpful in controlling blood glucose levels, but when you are taking them in combination, you are advised not to consume alcohol in large amounts. It is more beneficial for the patients if they take the medicine with the meal to avoid the possibility of any kind of stomach disturbance.

Missed Dose of Glimepiride and Metformin

It is advised to consume a missed dose as soon as you remember. You must skip your missed dose if the time of your next dose is very near. Trying to co compensate for a missed dose is never recommended as it may cause health complications in the patient.

Overdose of Glimepiride and Metformin

Overdose of these Glimepiride and Metformin can lead to other health problems in a patient.Breathing difficulty, dizziness, irregular heartbeat, and vomiting are some of the side effects that a patient can suffer from. Hence, overdosing of these medications is strictly forbidden.

Also Read: Long term side effects of metformin

WARNINGS

Pregnancy

Pregnant women are advised to take metformin and glimepiride only if their doctor recommends it. You should never start the combination of these drugs on your own, as it can cause serious complications.

You are advised to talk to your doctor first about the benefits and side-effects of taking metformin and glimepiride together before starting the course. After analyzing your condition, your doctor may suggest a different medication.

Nursing Mothers

Breastfeeding mothers should not take the combination of metformin and glimepiride, as studies have shown that it can pass into breast milk and cause health problems in babies. Self-medication of these drugs is completely forbidden for nursing mothers.

Summary

These drugs should not be consumed by lactating mothers and pregnant women as some studies have shown that these medications may pass on to the baby, which may cause complications. Hence, patients are recommended to see a doctor in such conditions to rule out the possibility of any complications.

Takeaway

Glimepiride And Metformin are very effective anti-diabetes medications. Doctors widely use these drugs to treat diabetes in patients. On time consumption of these drugs helps in maintaining blood sugar levels in patients. When a patient is kept on these drugs, the medical practitioner advises to follow a proper diet chart and exercise regime.

Also Read: Hba1c test full form

FAQs:

What is the safest drug to take for type 2 diabetes?

Experts believe that Metformin is still the safest and the most reliable drug to manage type-2 diabetes.

Is glimepiride bad for kidneys?

Glimepiride is safe and effective for diabetic patients with kidney functions. The raised plasma release of glimepiride with reduced kidney function is understandable on the basis of altered protein binding with an increase in unbound drug.

What is the best time of day to take glimepiride?

You are generally given glimepiride once in a day. This medicine produces better results when taken along with food. Usually, people take it right after breakfast in the morning. If you do not take breakfast, you should make sure to take it along with the first meal of the day.

When should I take metformin and glimepiride?

These medications should be taken after breakfast and dinner, or as suggested by the doctor. The highest dose per day should not exceed 8mg for glimepiride and 2000mg for metformin. Only a few patients see positive results with more than 6mg daily dosage of glimepiride.

How does glimepiride and metformin work together?

Taking Metformin and Glimepiride together can raise your risk of developing hypoglycemia, or low blood sugar. While being on this combination of drugs, you are advised to keep a close watch on your blood glucose levels to know if you need a dose adjustment. It is highly recommended to consult a doctor immediately if the patient experiences hypoglycemia while undergoing treatment.

References:

1. https://www.getroman.com/health-guide/metformin-interactions/
2. https://www.rxwiki.com/glimepiride
3. https://pubmed.ncbi.nlm.nih.gov/8960852/

Last Updated on April 9, 2022 by Dr. Damanjit Duggal 

Glimepiride + Metformin: View Uses, Side Effects and Medicines

>glimepiride + metformin

Information about Glimepiride + Metformin

How Glimepiride + Metformin works

Glimepiride + Metformin is a combination of two antidiabetic medicines: Glimepiride and Metformin. Glimepiride is a sulfonylurea which works by increasing the amount of insulin released by the pancreas in order to lower the blood glucose. Metformin is a biguanide which works by lowering glucose production in the liver, delaying glucose absorption from intestines and increasing the body’s sensitivity to insulin.

Common side effects of Glimepiride + Metformin

Nausea, Diarrhea, Headache, Upper respiratory tract infection, Dizziness, Flatulence

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Expert advice for Glimepiride + Metformin

• You have been prescribed this combination medicine as it can control blood sugar better than metformin alone.

• You should continue to exercise regularly, eat a healthy diet, and take your other diabetes medicines along with Glimepiride + Metformin.
• Take it with food to lower your chance of having an upset stomach.
• Monitor your blood sugar level regularly while you are taking this medicine. 
• It can cause hypoglycemia (low blood sugar level) when used with other antidiabetic medicines, alcohol or if you delay or miss a meal.  
• Inform your doctor about your diabetes treatment if you are due to have surgery under a general anesthetic.
• Tell your doctor immediately if you experience any deep or rapid breathing or if you have persistent nausea, vomiting, and stomach pain as Glimepiride + Metformin may cause a rare but serious condition called lactic acidosis, which is an excess of lactic acid in the blood.
• Your doctor may check your liver function regularly. Inform your doctor if you develop symptoms such as abdominal pain, loss of appetite, or yellowing of the eyes or skin (jaundice).

Frequently asked questions for Glimepiride + Metformin

Glimepiride + Metformin

Q. What are the recommended storage conditions for Glimepiride+Metformin?

Keep this medicine in the container or the pack it came in, tightly closed. Store it according to the instructions mentioned on the pack or label. Dispose of the unused medicine. Make sure it is not consumed by pets, children and other people.

Q. Can the use of Glimepiride+Metformin lead to lactic acidosis?

Yes, the use of Glimepiride+Metformin can lead to lactic acidosis. It is a medical emergency which is caused by increased levels of lactic acid in the blood. It is also known as MALA (Metformin-associated lactic acidosis). It is a rare side effect associated with the use of metformin and therefore, it is considered to be harmful for patients with underlying kidney disease, old age patients or who take large amounts of alcohol. Symptoms of lactic acidosis may include muscle pain or weakness, dizziness, tiredness, feeling of cold in arms and legs, difficulty in breathing, nausea, vomiting, stomach pain or slow heart rate. If you have these symptoms, stop taking Glimepiride+Metformin and consult your doctor immediately.

Q. What is Glimepiride+Metformin?

Glimepiride+Metformin is a combination of two medicines: Glimepiride and Metformin. This medicine is used in the treatment of type 2 diabetes mellitus (DM). It improves blood glucose levels in adults when taken along with proper diet and regular exercise. Glimepiride lowers the blood glucose levels by increasing the release of insulin from the pancreas. Metformin works by lowering the glucose production in the liver and improving insulin sensitivity. This combination is not indicated for the treatment of type 1 DM.

Q. What are the possible side effects of Glimepiride+Metformin?

The use of Glimepiride+Metformin is associated with common side effects like hypoglycemia (low blood sugar level), altered taste, nausea, stomach pain, diarrhea, headache and upper respiratory tract infection. Its use can also lead to serious but rare side effects like lactic acidosis. On long-term use it can also lead to Vitamin B12 deficiency.

Q. Can the use of Glimepiride+Metformin cause hypoglycemia?

Yes, the use of Glimepiride+Metformin can cause hypoglycemia (low blood sugar level). Symptoms of hypoglycemia include nausea, headache, irritability, hunger, sweating, dizziness, fast heart rate and feeling anxious or shaky. It happens more often if you miss or delay your food, drink alcohol, over-exercise or take other antidiabetic medicine along with it. So, regular monitoring of the blood sugar level is important. Always keep a quick source of sugar like glucose tablets, honey or fruit juice with you.

Q. Can the use of Glimepiride+Metformin lead to Vitamin B12 deficiency?

Yes, the use of Glimepiride+Metformin can cause Vitamin B12 deficiency on long-term use. It interferes with the absorption of Vitamin B12 in the stomach. If untreated, it may cause anemia and nerve problems and the patient can experience tingling sensation and numbness in hands and feet, weakness, urinary problems, change in mental status and difficulty in maintaining balance (ataxia). To avoid such problems, some researchers suggest an intake of Vitamin B12 from outside sources at least once every year.

Q. Is it safe to take alcohol while I am also taking Glimepiride+Metformin?

No, it is not safe to take Glimepiride+Metformin along with alcohol, as it may lower your blood sugar levels and lead to hypoglycemia. It can also increase the chances of lactic acidosis.

The use of a combination of fixed doses of glimepiride and metformin in patients with type 2 diabetes mellitus. Results of a Russian observational study | Zaitseva

Annotation

Therapy with fixed doses of combination drugs demonstrates high efficacy and safety and may increase patient adherence to therapy.
Purpose.
Efficacy and safety of a fixed-dose combination of glimepiride and metformin (Amaryl?M) in patients with type 2 diabetes mellitus (T2DM) in a multicentre, open, prospective, observational study.
Materials and methods.
.
The study included 1200 patients who did not achieve glycemic control targets while taking metformin and/or glimeperide for at least 12 weeks. HbA _1c , fasting plasma glucose and 2 hours after meals, body mass index (BMI), number of hypoglycemia and other adverse events were assessed in dynamics.
Results.
After 12 weeks of Amaryl? M, baseline HbA _1c (8.24?0.42%) significantly decreased and amounted to 7.48?0.48%; after 24 weeks, the level of HbA _1c was 6.88?0.56%. 65.1% of patients achieved HbA _1c ?7% by the end of the study. The decrease in fasting glycemia and postprandial glycemia by the end of the study amounted to 1.45-1.14 mmol/l and 2.17-1.27 mmol/l, respectively. No episodes of severe hypoglycemia were noted. BMI significantly decreased by 0.85?1.28 kg/m ² (p<0.001).
Conclusion.
The use of a combination of fixed doses of metformin and glimepiride (Amaryl?M) can significantly improve the state of carbohydrate metabolism in patients with type 2 diabetes. Such therapy is safe due to the low risk of developing hypoglycemic conditions, the absence of side effects and a negative effect on body weight.

.

Keywords

type 2 diabetes,
glycated hemoglobin,
glimepiride,
metformin,
Amaril?

For citation:

Zaitseva N. V., Yarek-Martynova I.R. The use of a combination of fixed doses of glimepiride and metformin in patients with type 2 diabetes mellitus. Results of a Russian observational study. Diabetes mellitus . 2015;18(2):84-88. https://doi.org/10.14341/DM2015284-88

For citation:

Zaytseva N.V., Jarek-Martynova I.R. Evaluation of fixed dose combination of glimepiride and metformin in patients with type 2 diabetes. Results of Russian observational study. Diabetes mellitus . 2015;18(2):84-88.
(In Russ.)

https://doi.org/10.14341/DM2015284-88

Relevance

Type 2 diabetes mellitus (DM2) is one of the most common chronic diseases that leads to a decrease in life expectancy and quality of life. The incidence of type 2 diabetes is steadily increasing due to an increase in the number of obese patients and life expectancy.

Since the initial disorders of carbohydrate metabolism are often asymptomatic, when DM2 is detected, many patients already have micro- and macrovascular complications. In T2DM, target glycemic levels have been clearly defined, the achievement of which leads to a decrease in the incidence of late complications [1]. Treatment based on the use of drugs with a high antihyperglycemic effect, a minimum number of side effects, and convenient for continuous use, is the best tactic leading to improved control of diabetes [2].

Carbohydrate metabolism disorders in T2DM are based on insulin resistance (inadequate biological response of cells to a sufficient physiological level of insulin in the blood) and pancreatic β-cell dysfunction. The main goals of T2DM treatment include achieving blood glucose levels as close to normal as possible without a high risk of hypoglycemia, maintaining β-cell function, and reducing insulin resistance. National and international programs for the treatment of DM2 are annually updated and supplemented taking into account pathogenetic approaches to therapy and newly obtained data.

In 2015, the Council of Experts of the Russian Association of Endocrinologists (RAE) updated the Consensus on the initiation and intensification of hypoglycemic therapy for type 2 diabetes [3]. International clinical guidelines are fully included in the 7th edition of the Algorithms for Specialized Medical Care for Patients with Diabetes in the Russian Federation as part of the federal program “Diabetes Mellitus” [4]. In 2015, updated ADA/EASD (American Diabetes Association/European Association for the Study of Diabetes) recommendations were issued, also based on current views on the treatment of patients with type 2 diabetes [5].

According to the latest recommendations, an individual approach to the patient and, accordingly, the determination of an individual target level of glycated hemoglobin (HbA1c) should be the basis for choosing a strategy for hypoglycemic therapy (CCT).

Mechanisms of action of hypoglycemic drugs are different, but in general they are aimed at eliminating the three main metabolic disorders that lead to hyperglycemia in T2DM: impaired insulin secretion by the pancreas, peripheral insulin resistance and excessive production of glucose by the liver.

Lifestyle modification remains the first step towards T2DM treatment, due to the beneficial effects of weight loss and increased physical activity on carbohydrate and lipid metabolism. However, only a small number of patients manage to maintain normoglycemia through non-pharmacological interventions. Therefore, simultaneously with lifestyle changes, it is advisable to start metformin therapy, the action of which is aimed at the main causes of DM2 – insulin resistance and hyperproduction of glucose by the liver, for which it is called the “gold” standard in the treatment of DM2. An alternative for metformin intolerance may be dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists. If this step is ineffective, which is manifested by the persistence of a non-target HbA1c level for 6 months or its decrease by less than 0.5%, a transition to the next stage is recommended.

The second stage is the intensification of drug therapy. In this case, the choice of the drug is determined by the level of glycated hemoglobin (HbA1c), and also takes into account the characteristics of the course of DM2, comorbidities, age, and duration of diabetes.

All this together forms individual target indicators of glycemia. The latest recommendations of the International Diabetes Federation (IDF – International Diabetes Federation, 2012) [6], ADA (2014) [7], RAE (2011) [3], based on large-scale international clinical trials (ADVANCE – Action in Diabetes and Vascular Disease -Preterax and Dimicron MR Controlled Evaluation, ACCORD – Action to Control Cardiovascular Risk in Diabetes, VADT – Veteran Affairs Diabetes Trial), much attention is paid to hypoglycemic conditions and their consequences for patients’ health. It has been proven that cardiovascular complications and death are more common among patients with an intensified decrease in glycemic levels and frequent hypoglycemic episodes (especially severe hypoglycemia) [8]. Priority in this clinical situation should be given to agents with minimal risk of hypoglycemia.

With an HbA1c level of 7.6-9.0% already at the onset, combination therapy should be started immediately. Sulfonylureas (PSMs), like metformin, have half a century of clinical experience.

The mechanism of action is maximally realized only with the preserved function of the insular apparatus of the pancreas and is due to the binding of PSM to specific receptors of the plasma membrane of β-cells integrated into the structure of ATP-dependent potassium channels of plasma membranes. Glimepiride is a PSM characterized by a higher rate of association and dissociation with the β-cell receptor (2.5–3.0 and 8–9times higher, respectively) than other drugs of the second generation [9]. This explains a better reduction in postprandial glycemia (PPG) and a lower risk of hypoglycemic conditions. In addition, rapid depletion of the insular apparatus of the pancreas is prevented.

Purpose

A registry study was initiated in the Russian Federation to determine the efficacy and safety of a fixed dose combination (FDC) of glimepiride and metformin (Amaryl® M) in everyday clinical practice in patients with type 2 diabetes with an HbA1c level of 7 ,6–9%. His main task was to assess the change in HbA1c levels 3 and 6 months after the use of FDA glimepiride and metformin in patients with type 2 diabetes.

Secondary goals were to determine the percentage of patients who achieved HbA1c≤6.5 and HbA1c≤7% after 3 and 6 months of taking FDA glimepiride and metformin, as well as to assess the change in fasting plasma glucose (FPG) and PPG after 3 and 6 months of taking FDA. glimepiride and metformin; assessment of the average daily dose of FDC glimepiride and metformin after 3 and 6 months; assessment of BMI after 6 months of FDC use of glimepiride and metformin; assessment of the frequency of confirmed episodes of hypoglycemia per 1 patient per month after 3 and 6 months of taking FDA glimepiride and metformin. In addition, adverse events (AEs)/serious AEs were assessed.

Design and Methods

The clinical study involved 119 centers from various regions of Russia (the study was conducted in the following regions of the Russian Federation: Western and Eastern Siberia, North-West Russia, Central Federal District, Northern and Southern Volga, Ural, South of Russia, Moscow region).

All patients signed informed consent to participate in the study, which included 1200 DM2 patients who met the inclusion/exclusion criteria, of which 1169 completed the study. The study included patients over 18 years of age who had received metformin and/or glimepiride therapy for at least 12 weeks prior to enrollment and did not reach an HbA1c level of less than 7.5%. Patients received FDC of glimepiride and metformin (Amaryl® M) for 6 months. The initial dose of Amaryl® M for all patients with type 2 diabetes was 2 mg/500 mg. Patients received a dose of the drug 1 time per day immediately before breakfast or, in case of skipping, before the next main meal. Efficacy was analyzed after 3 months in a group of 1190 (99.2%) patients and after 6 months – in the group of 1169 (97.4%) patients. Safety analysis was performed in the group of patients who took at least one dose of FDA glimepiride and metformin as prescribed by a doctor (1190 patients), and in the group of patients who completed the study in accordance with the protocol (1169 patients).

Because the program was observational, all statistical methods used were descriptive and used for the purposes of the study. No measurable indicators or statistical hypotheses were defined in advance to limit the risk of false positive results due to the possible high variability and diversity of the data studied.

Results

The study included 373 men (mean age 54.8 ± 9.8 years) and 827 women (mean age = 57.8 ± 9.6 years). The mean duration of T2DM was 3.5±3.3 years (median 2.4 years). Patients had a mean BMI of 32.5±3.9 kg/m2 (median 32.4 kg/m2) at baseline. An analysis of the degree of obesity in the studied population showed that 48% had the first degree of obesity, 27% – the second; 23% were overweight and 2% were normal. Body weight in men was 95.7±13.6, for women – 87.9±12.5 kg. The mean waist circumference (WC) in men was 106.9±15.6 cm, in women it was 101.2±14.5 cm. taking a combination of non-fixed doses of metformin and glimepiride. Mean levels of HbA1c were 8.

24±0.42% (median 8.2%), FPG – 8.45±1.34 (median – 8.3 mmol/l), PPG – 10.9±2.12 mmol /l (median – 10.5 mmol/l).

At baseline, one tablet of Amaryl® M per day was administered to all patients who self-titrated the dose according to the algorithm recommended by the physician, taking into account the results of self-monitoring of fasting glycemia. After 3 months of therapy, a two-fold increase in the initial dose was noted in 20.2% of cases, three or more times – in 1.7%. At the end of the study, 36.4% of patients took 2 tablets of the drug, 3.5% – 3 or more. Most patients continued to take the original recommended dose of the drug.

3 and 6 months after the initial stage, the HbA1c level decreased markedly – from 8.24±0.42% initially to 7.48±0.46 and 6.88±0.56%, respectively. The average decrease in HbA1c in absolute terms after 3 months of therapy was -0.76±0.47%, after 6 months -1.35±0.57% (Fig. 1).

Changes from baseline were 9.16±5.53 and 16.3±6.56%, respectively.

The proportion of patients who achieved HbA1c≤6.5% was 5.0% and 26.9% at 3 and 6 months, respectively (p<0.001). The effectiveness of the drug is also confirmed by the high percentage of patients who reached the level of HbA1c≤7.0%, 22.7 and 65.1%, respectively (p<0.001) (Fig. 2).

FPG level decreased on average from 8.45±1.34 to 7.00±1.04 mmol/l after 3 months and to 6.27±0.79 mmol/l after 6 months. The average decrease reached -1.45±1.14 and -2.17±1.27 mmol/l, which in relative terms was -16.3±11.0 and -24.6±11.6% of the initial value respectively.

The level of postprandial glucose decreased from 10.9±2.12 mmol/l initially to 8.68±1.63 and 7.78±1.23 mmol/l after 3 and 6 months, respectively. The changes were -2.22±1.67 and -3.12±1.79 mmol/l, which in relative terms reached -19.2±13.0 and -27.1±12.6% of the initial value (Fig. 3).

The average dose of FDC of glimepiride and metformin did not change significantly within 6 months from the start of therapy and after 6 months was 2.

90±1.25 mg/day (median 2.0 mg) and 726±312 mg/day (median – 500 mg), respectively (p>0.05). At the end of the study, 699/1169 (59.8%) patients continued to take the original recommended dose of the drug. A significant increase in the dose of the drug was not observed.

The use of the drug had a positive effect on the dynamics of BMI and WC. By the end of the study, BMI significantly (p

<0.001) decreased by 0.85±1.28 kg/m2 (-2.61±3.86% of the baseline) and amounted to 31.6±3.8 compared to 32, 5±3.9kg/m2. WC in women decreased over 6 months of therapy by -2.52±3.05% and amounted to 98.5±14.1 cm compared with 101.2±14.5 cm at the screening stage (p<0.001). In men, WC also significantly decreased and amounted to 104.3±15.2 cm compared to 106.9±15.4 cm at the initial stage (p<0.001). Compared with the initial value, WC decreased by -2.52±3.05% in women and by -2.12±3.49% in men.

Among patients who took the drug at least once, the proportion of episodes of asymptomatic hypoglycemia was 84/1190 (7.

06%), symptomatic hypoglycemia – 63/1190 (5.29%) and nocturnal symptomatic hypoglycemia – 11/1190 (0.92%). Among patients who completed the study according to the protocol, the proportion of patients with asymptomatic hypoglycemia was 84/1169 (7.19%), symptomatic hypoglycemia – 61/1169 (5.22%) and nocturnal symptomatic hypoglycemia – 9/1169 (0.78%) . No cases of severe hypoglycemia were recorded during the entire study period.

1.02% of patients in the at least 1 dose group and 1.03% of patients in the per-protocol study group were hospitalized for DM2. The average number of days in the hospital for type 2 diabetes was 12.9±1.62. There were no cases of contacting the ambulance service for DM2 (0%). No other AEs were reported during the entire study period.

Discussion

This study examined the results of the use of metformin and PSM (glimepiride) in the form of FDC in patients with T2DM who did not achieve the target indicators of carbohydrate metabolism during therapy with metformin and/or glimepiride.

The study demonstrated that the use of the drug Amaryl®M leads to a significant improvement in HbA1c, FPG, PPG. It should be noted that such therapy does not have a negative effect on body weight (in some cases, there is a decrease in BMI and WC), and these are the most important parameters that in themselves can lead to a deterioration in carbohydrate metabolism compensation.

In addition to the effectiveness of SST, according to current recommendations, it is necessary to assess the safety of the therapy. To this end, the frequency and severity of emerging cases of hypoglycemia are strictly controlled. The study clearly demonstrated a low risk of hypoglycemia while taking metformin and glimepiride, which indicates a high safety of this combination for patients with type 2 diabetes.

It should be noted that the non-interventional design of the studies is a possible limitation in relation to the estimation of body weight, and may also explain the small number of reported hypoglycemia.

The results are consistent with those of other studies. Thus, in the Charpentier study [9], it was shown that the combination of glimepiride and metformin, the use of which was started in patients with HbA1c≥7.0%, caused the achievement of glycemic control (HbA1c -0.74%), better than the use of glimepiride monotherapy. or metformin. In this study, glimepiride therapy was shown to be as safe as metformin monotherapy, although the incidence of hypoglycemic episodes was higher in the combination group than in the metformin group [10]. The effectiveness of the combination of glimepiride and metformin was proven in a study involving patients with type 2 diabetes without adequate control on the background of metformin monotherapy. Twelve weeks of therapy demonstrated the effectiveness of the combination in terms of improving (reducing) the levels of FPG and PPG, as well as HbA1c. The latter was the main efficacy parameter in the study and decreased during therapy from 8.35±0.93 to 7.

65±1.70% (p<0.001). The proportion of patients with a decrease in HbA1c≤6.5% and/or HbA1c≤7% was 65.79% [11].

The advantage of using FDC over taking a combination of drugs in individually adjusted dosages is to increase patient adherence to therapy. This was shown in a retrospective study by Melikian et al. and in the study by Penfornis et al. In the first study, the adherence of patients in the group receiving FDA of glibenclamide and metformin was 77%, in the group of combination therapy with drugs in individually selected dosages – 54% [12]. In the second study, it was shown that starting therapy with FDA or switching patients to FDA was accompanied by a significant increase in adherence to therapy [13].

In addition, there is evidence of a more pronounced efficacy of the components in the composition of FDA compared to the effectiveness of drugs in individually selected dosages in the combination, due to changes in the pharmacokinetic and pharmacodynamic properties of the components.

For example, Stephen R. Donahue et al. showed that the use of FDC glibenclamide and metformin increases Cmax by 16% and leads to a significant decrease in the intensity of the increase in PPG levels compared with taking a combination of non-fixed doses of drugs [14].

Conclusion

Combination therapy with metformin and glimepiride can improve carbohydrate metabolism in patients with type 2 diabetes. The use of this combination of drugs demonstrates a high level of safety due to the low risk of hypoglycemia (symptomatic, nocturnal, asymptomatic and especially severe) and the absence of other AEs. The indisputable advantage of this therapy is the lack of weight gain, which has a positive effect on carbohydrate metabolism. In addition, the use of fixed combinations of drugs, such as Amaryl®M, makes the treatment regimen more convenient and improves patient compliance.

Funding and conflict of interest information

The authors declare no conflicts of interest in the preparation of this publication.

Acknowledgments

Thanks to all investigators who participated in the GLMET_L_06048 clinical study.

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About authors

Natalya Vladislavovna Zaitseva

FGBU Endocrinological Research Center, Moscow

Russia

c. m.s., senior researcher departments of diabetic nephropathy and hemodialysis

Conflict of interest:

The authors declare no conflicts of interest in the preparation of this publication.

Ivona Renata Yarek-Martynova

FGBU Endocrinological Research Center, Moscow

Russia

Ph.D., leading researcher Department of Diabetic Nephropathy and Hemodialysis, Federal State Budgetary Institution Endocrinological Research Center, Moscow

Conflict of interest:

The authors declare no conflicts of interest in the preparation of this publication.

Additional files

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