What is glimepiride used to treat: Glimepiride: MedlinePlus Drug Information
Amaryl (Glimepiride) – Functio, Suitability, Side Effects & Safety
Amaryl is an oral blood sugar-lowering drug that is used to treat patients with type 2 diabetes.
It contains the active ingredient glimepiride and belongs to the sulphonylurea class of diabetes medicines, which work by boosting the secretion of natural insulin and increasing the body’s sensitivity to the blood sugar-regulating hormone.
- Trade name: Amaryl
- Generic name: Glimepiride
- Drug class: Sulphonylureas
- Manufacturer: Sanofi-Aventis
Mechanism of action
Amaryl helps reduce the amount of glucose in your blood by stimulating the release of insulin from the pancreas into the blood and encouraging the use of sugar in your blood by the cells that need it.
Who is Amaryl suitable for?
Amaryl is indicated for treatment of adults with type 2 diabetes who are unable to achieve glycemic (blood glucose) control through diet and exercise alone.
Amaryl can be taken on its own (monotherapy) or in combination with metformin (sitagliptin) or insulin when these have not proved effective enough on their own.
Who is it not suitable for?
As with any drug, Amaryl is not suitable for everyone – some people should never use it while others should only use it with special care.
Glimepiride should not be prescribed to people who:
- are allergic or sensitive to or have had a reaction to any of the ingredients in the medicine
- are allergic or sensitive to or have had a bad reaction to sulphonylureas or sulphonylurea-like substances in the past
- have type 1 diabetes
- have ketoacidosis
- have kidney, liver or thyroid problems
- are pregnant or breastfeeding
- are on dialysis
- have adrenal or pituitary gland problems
- have glucose-6-phosphate dehydrogenase deficiency
How and when to take Amaryl
Amaryl tablets are available in 1mg, 2mg, 3mg and 4mg doses. Normally a single daily dose of glimepiride is sufficient, and it is recommended that this dose be taken whole with some liquid shortly before or during breakfast or – if you skip breakfast – shortly before or during your first main meal.
Your GP will determine the dose and frequency of dosage depending on your blood sugar levels, and these instructions will be printed on the dispensing label attached to your medication.
If you forget to take a dose, start your medication regimen again with your next meal. Do not take increase your dose to make up for a missed one.
Glimepiride tablets should always be kept in the original container and stored at room temperature. You must also make sure the medicine is kept out of the sight and reach of children.
Common adverse effects of Amaryl include:
Very rare side effects include:
- Hypersensitivity reactions including breathing difficulties, lowered blood pressure or shock
- Liver problems
- Metabolic problems
- Stomach pain and discomfort
Please note this is not a complete list of side effects and others may occur. A full list can be found in the patient information leaflet that is enclosed with the medication.
What to do in the event of an overdose
Taking more doses of some medicines than stated in the instructions can be harmful. In case of an overdose, you should seek emergency medical attention.
There are a number of different types of medicines that may interact with glimepiride. Some of these may reverse the action of Amaryl, while others that have the same blood sugar-lowering effect may increase the risk of hypoglycaemia.
Medicines that interact include:
- ACE inhibitors
- Anabolic steroids
- Cytochrome P450 enzyme inducers and inhibitors
- Oestrogens and progestogens
- Oral hypoglycemics
- Thiazide diuretics
- Thyroid stimulating agents
Please note this is not a comprehensive list and other types of medication may affect the action of glimepiride.
If you are taking any of medications listed above, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want to adjust the dose of one or both of the medications; change one of the medications to another; or stop one of the drug treatments.
Glimepiride – tabletwise.net
Severe Low Blood Sugar Level
Patients with severe low blood sugar level are at an increased risk when using this medicine. Such patients may have an increased risk of loss of consciousness or convulsions and may result in temporary or permanent abnormality in the functioning of the brain or can be possibly fatal. Use necessary precautions while starting and increasing the dose ofGlimepiridein elderly patients, patients with abnormal functioning of the kidneys and in patients who are on other anti-diabetic medicines.
Allergy to Glimepiride
Patients who are allergic toGlimepirideare at an increased risk when using this medicine.Glimepiridecan cause allergic reactions including life-threatening allergic reaction, swelling of the lower layer of the skin, severe skin reaction (called, stevens-johnson syndrome). If an allergic reaction occurs, discontinue the use of Glimepiride, and alternative treatment for low blood sugar level should be taken.
Enzyme (Glucose 6-Phosphate Dehydrogenase) Deficiency
Patients with enzyme (glucose 6-phosphate dehydrogenase) deficiency are at an increased risk when using sulfonylureas. Use of sulfonylureas can cause red blood cells deficiency in these patients. Precaution should be taken in patients with enzyme (glucose 6-phosphate dehydrogenase) deficiency and use of non-sulfonylurea should be considered.
Patients with inherited disorders such as reduced or absent activity of lactase (galactose intolerance), enzyme (Lapp lactase) deficiency or defect in glucose and galactose transport across the intestinal are at increased risk while using this medicine. The use of this medicine is avoided in patients with lactose intolerance as it contains lactose monohydrate.
Alterations in Diet in Patients Using Glimepiride
When meals are taken at the irregular interval or skipped altogether, treatment withGlimepiridemay increase the risk of low blood sugar levels. This medicine cause headache, nausea, vomiting, insomnia, restlessness, aggressiveness, depression, alertness and reaction time, confusion, speech and visual disorders, speech problems, tremor, muscular weakness, sensory disturbances, dizziness, helplessness, loss of self-control, disturbance in mental abilities, convulsions, sleeplessness, slow heart rate, sweating, decreased or increased heartbeat, clammy skin, anxiety, rapid heart rate, high blood pressure, palpitation, and chest pain.Glimepirideshould be taken shortly before or during a meal.
Abnormal Functioning of the Kidney
Such patients are at an increased risk when using this medicine. Use ofGlimepiridecan cause low blood sugar level in these patients. Use of insulin is indicated in patients with abnormal functioning of the kidneys.
Severe Abnormal Functioning of the Liver
Patients with severe abnormal functioning of the liver are at an increased risk when using this medicine. Use ofGlimepiridecan cause low blood sugar level in these patients. Regular monitoring of liver and blood parameters such as leucocytes and thrombocytes are required during treatment withGlimepiridetablets.
What is The Difference Between Glimepiride and Metformin?
What is Glimepiride (Amaryl)?
Glimepiride is a prescription drug that is available as oral tablet. This drug is commonly prescribed with an exercise and diet program to control blood glucose in type 2 diabetic patients. Glimepiride is also sold under the brand name Amaryl. Amaryl belongs to a class of medication called sulfonylureas. Sulfonylureas work by increasing the amount of insulin that is released by the pancreas. This helps to reduce high amounts of blood glucose. This medication should be taken orally with breakfast once every day.
What is Metformin?
It is an oral diabetes medication that is taken by patients with type 2 diabetes. Metformin is marketed under the brand name Glucophage and belongs to a class of medication called biguanides. The medication works by improving your cells’ response to the natural insulin produced by the pancreas. This oral drug also works by reducing the amount of glucose that is released by your liver and that is absorbed by the stomach. Glucophage can be prescribed as a combination therapy with other diabetes drugs, but should not be used to treat type 1 diabetic patients. You should not take this medicine if you have diabetic ketoacidosis or severe kidney disease.
Similarities and differences between Glimepiride and Metformin
Glimepiride and metformin are oral prescription drugs that are used to control blood sugar in type 2 diabetic patients. Both medications are normally taken once every day with the first main meal. Your dosage will be determined by your health-care provider. These meds can be used alone or as part of a combination therapy to control high blood sugar in type 2 diabetic people. When it comes to side effects, both glimepiride and metformin share the same side effects that include nausea, headache, and weakness.
Amaryl is available in pill form while Glucophage comes in pill, extended release pill and liquid form. As well, both medications come in different strengths. Glimepiride is usually prescribed to treat type 2 diabetic patients. On the other hand, doctors also prescribe metformin to reduce the risk of developing diabetes in patients with polycystic ovary syndrome (PCOS).
Disclaimer: Please note that the contents of this community article are strictly for informational purposes and should not be considered as medical advice. This article, and other community articles, are not written or reviewed for medical validity by Canadian Insulin or its staff. All views and opinions expressed by the contributing authors are not endorsed by Canadian Insulin. Always consult a medical professional for medical advice, diagnosis, and treatment.
Amaryl (glimepiride) Drug / Medicine Information
Consumer Medicine Information (CMI)
What is in this leaflet
This leaflet answers some common questions about Amaryl.
It does not contain all the available information. It does not take the place of talking to your doctor, pharmacist or diabetes
All medicines have risks and benefits. Your doctor has weighed the risks of you taking Amaryl against the benefits they expect
it will have for you.
If you have any concerns about taking this medicine, ask your doctor or pharmacist.
Keep this leaflet with the medicine.
You may need to read it again.
What Amaryl is used for
Amaryl is used to control blood glucose in patients with type 2 diabetes mellitus.
Amaryl is used when healthy eating and increased physical activity are not enough to control your blood glucose.
Amaryl can be used alone, or together with insulin or other medicines for treating diabetes.
How it works
Amaryl lowers high blood glucose by increasing the amount of insulin produced by your pancreas.
Amaryl belongs to a group of medicines called sulfonylureas.
If your blood glucose in not controlled properly, you may experience hypoglycaemia (low blood glucose – a “hypo”) or hyperglycaemia
(high blood glucose).
Low blood glucose can occur suddenly. Signs may include:
weakness, trembling or shaking
lightheadedness, dizziness, headache or lack of concentration
tearfulness or crying
numbness around the lips and tongue
If not treated promptly, these may progress to:
loss of co-ordination
loss of consciousness or seizures
High blood glucose usually occurs more slowly than low blood glucose. Signs of high blood glucose may include:
lethargy or tiredness
passing large amounts of urine
High blood glucose can lead to serious problems with your heart, eyes, circulation or kidneys.
Ask your doctor if you have any questions about why this medicine has been prescribed for you.
This medicine is only available with a doctor’s prescription.
There is no evidence that Amaryl is addictive.
Before you take Amaryl
When you must not take it
Do not take Amaryl if:
you have an allergy to:
related medicines such as sulfur antibiotics or thiazide diuretics
any of the ingredients listed at the end of this leaflet
Symptoms of an allergic reaction to Amaryl may include skin rash, itchiness, shortness of breath, or difficulty breathing.
If you are not sure you have an allergy to Amaryl, check with your doctor.
you have previously had a reaction to glimepiride or any other sulfonylurea or sulfonamide
you have or have had any of the following conditions:
type 1 diabetes mellitus
diabetic coma or pre-coma
severe kidney disease or if you require dialysis
severe liver failure
If you are not sure if you have any of the above, ask your doctor.
you are pregnant or intend becoming pregnant
Insulin is more suitable for controlling blood glucose during pregnancy. Your doctor will replace Amaryl with insulin.
you are breastfeeding or plan to breastfeed
Amaryl passes into breast milk and therefore there is the possibility that the breastfed baby may be affected.
the packaging is torn or shows signs of tampering (or the tablets do not look quite right)
the expiry date printed on the pack has passed
If you take this medicine after the expiry date has passed, it may not work as well.
Do not give Amaryl to children.
There is not enough experience with the use of Amaryl in children.
If you are not sure whether you should start taking Amaryl, talk to your doctor or pharmacist.
Before you start to take it
Tell your doctor if:
you have any allergies to any other medicines or any other substances such as foods, preservatives or dyes
you are breastfeeding or plan to breastfeed
Amaryl passes into breast milk and therefore there is the possibility that the breastfed baby may be affected.
you have or have had any of the following medical conditions
a history of diabetic coma
adrenal, pituitary or thyroid problems
glucose-6-phosphate dehydrogenase (G6PD) deficiency
you drink alcohol in any amount
you do not eat regular meals
you do a lot of exercise or you do heavy exercise or work
you are ill or feeling unwell
Alcohol, diet, exercise and your general health all strongly affect the control of your diabetes.
you are taking any other anti-diabetic treatment
If you have not told your doctor or pharmacist about any of the above, tell them before you start taking Amaryl.
Taking other medicines
Tell your doctor, pharmacist or diabetes educator if you are taking any other medicines, including any that you buy without
a prescription from your pharmacy, supermarket or health food shop.
Some medicines may lead to low blood glucose (hypoglycaemia) by increasing the blood glucose-lowering effect of Amaryl. These
other medicines used to treat diabetes
some medicines used to treat reflux and stomach ulcers
some anti-inflammatory agents, such as ibuprofen and naproxen
some medicines used to treat arthritis and gout
some blood pressure lowering medicines, such as beta-blockers and ACE inhibitors
some medicines used to treat blood clots, blood vessel problems and irregular heart rhythms
some cholesterol-lowering and weight reduction medicines
some cancer and organ transplant treatments
Some medicines may lead to loss of control of your diabetes by weakening the blood glucose-lowering effect of Amaryl. These
some antibiotics, such as rifampicin
some blood pressure, cholesterol and heart medications
some medicines used to treat reflux and stomach ulcers
some medicines used to treat epilepsy
corticosteroids, glucagon, adrenaline and other hormonal therapies
some asthma medicines, preparations for coughs and colds, and weight reduction medicines
some fluid and glaucoma medications
large doses of laxatives
some psychiatric and sedating medications
Amaryl may change the effects of other medicines. These include:
coumarin derivatives, which are used to prevent blood clots
Some medicines may hide the symptoms of low blood glucose (hypoglycaemia). These include:
certain heart medications, such as beta-blockers
You may need different amounts of your medicine or you may need to take different medicines. Your doctor, pharmacist or diabetes
educator can tell you what to do if you are taking any of these medicines. They also have a complete list of medicines to
be careful with or avoid while taking Amaryl.
Ask your doctor or pharmacist if you are not sure if you are taking any of these medicines.
How to take Amaryl
Follow all directions given to you by your doctor, pharmacist or diabetes educator carefully.
They may differ from the information contained in this leaflet.
If you do not understand the instructions on the box, ask your doctor or pharmacist for help.
How much to take
Your doctor will tell you how many tablets to take each day. Your doctor may increase or decrease the dose, depending on your
blood glucose levels.
How to take it
Swallow the tablets whole with a glass of water.
When to take it
You must make sure that you take Amaryl just before or with a meal.
Amaryl tablets are usually taken once a day, immediately before breakfast. If you eat only a light breakfast, you should delay
taking the tablet until after the first main meal of the day (eg lunch).
Do not skip meals while taking Amaryl.
How long to take it
Continue to take Amaryl for as long as your doctor recommends. Make sure you keep enough Amaryl to last over weekends and
Amaryl will help control your diabetes but will not cure it. Therefore, you may have to take it for a long time.
If you forget to take it
If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise,
take it as soon as you remember, and then go back to taking your medicine as you would normally.
Missed doses can cause high blood glucose (hyperglycaemia).
If you are not sure whether to skip the dose, talk to your doctor or pharmacist.
Do not take a double dose to make up for the dose that you missed.
If you double a dose, this may cause low blood glucose (hypoglycaemia).
If you take too much (overdose)
Immediately telephone your doctor or pharmacist or the Poisons Information Centre (13 11 26 in Australia; 0800 POISON or 0800
764 766 in New Zealand), or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may
have taken too much Amaryl.
Do this even if there are no signs of discomfort or poisoning.
You may need urgent medical attention.
If you take too much Amaryl, you may experience the symptoms of low blood glucose (hypoglycaemia).
At the first signs of hypoglycaemia, raise your blood glucose quickly by taking one of the following:
5-7 jelly beans
3 teaspoons of sugar or honey
1/2 can of a sugar-containing soft drink
2-3 concentrated glucose tablets
Unless you are within 10 to 15 minutes of your next meal, follow up with extra carbohydrates, e.g. plain biscuits, fruit or
milk, when over the initial symptoms.
Taking this extra carbohydrate will prevent a second drop in your blood glucose level.
If not treated quickly, these symptoms may progress to loss of co-ordination, slurred speech, confusion, loss of consciousness
While you are using Amaryl
Things you must do
If you become pregnant while you are taking Amaryl, stop taking it and tell your doctor immediately.
If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking Amaryl.
Tell all doctors, dentists and pharmacists who are treating you that you are taking Amaryl.
If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are taking Amaryl.
Make sure all friends, relatives, workmates or carers know that you have diabetes. Make sure they can recognise the symptoms
of hypoglycaemia and know how to treat them. Provide them with the telephone number for your doctor, the Poisons Information
Centre (13 11 26 in Australia; 0800 POISON or 0800 764 766 in New Zealand) and Emergency Services.
Always carry some sugary food or drink with you.
If you experience any of the symptoms of low blood glucose (hypoglycaemia), immediately eat some sugary food or have a drink,
e.g. lollies, biscuits or fruit juice. Diet and low calorie soft drinks do NOT contain sugar and are unsuitable to take for
If you are elderly or are taking other medicines for diabetes, the risk of hypoglycaemia is increased.
The risk of hypoglycaemia is also increased in the following situations:
too much Amaryl
too much or unexpected exercise
delayed meal or snack
too little food
If you experience any of the signs of high blood glucose (hyperglycaemia), contact your doctor immediately.
The risk of hyperglycaemia is increased in the following situations:
undiagnosed or uncontrolled diabetes
illness, infection or stress
too little Amaryl
certain other medicines
too little exercise
sudden immobilisation, e.g. after an accident
eating more carbohydrate than normal
If you become ill or experience extra stress, injury, fever, infection or need surgery, tell your doctor.
Your blood glucose may become difficult to control at these times. Your doctor may decide to change your treatment and use
insulin instead of Amaryl.
Make sure you check your blood glucose levels regularly.
This is the best way to tell if your diabetes is being controlled properly. Your doctor or diabetes educator will show you
how and when to do this.
Visit your doctor for regular checks of your eyes, feet, kidneys, heart, circulation, blood and blood pressure.
Carefully follow your doctor’s and/or dietician’s advice on diet, drinking alcohol and exercise.
If you drink alcohol while taking Amaryl, you may get flushing, headache, breathing difficulties, rapid heart beat, stomach
pains or feel sick and vomit.
Tell your doctor immediately if you notice the return of any symptoms you had before starting Amaryl.
These may include lethargy or tiredness, headache, thirst, passing large amounts of urine and blurred vision.
These may be signs that Amaryl is no longer working, even though you may have been taking it successfully for some time.
Things you must not do
Do not give Amaryl to anyone else, even if they have the same condition as you.
Do not skip meals while taking Amaryl.
Things to be careful of
Protect your skin when you are in the sun, especially between 10am and 3pm.
Amaryl may cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight may cause a skin rash,
itching, redness, or a severe sunburn.
If outdoors, wear protective clothing and use a 15+ sunscreen. If your skin does appear to be burning, tell your doctor immediately.
If you have to be alert, e.g. when driving, be especially careful not to let your blood glucose levels fall too low.
Low blood glucose levels may slow your reaction time and affect your ability to drive or operate machinery. Drinking alcohol
can make this worse. However, Amaryl by itself is unlikely to affect how you drive or operate machinery.
Make sure you know how you react to Amaryl before you drive a car, operate machinery or do anything else that could be dangerous
if you are dizzy or light-headed. If this occurs, do not drive.
If you are travelling, it is a good idea to:
wear some form of identification showing you have diabetes
carry some form of sugar to treat hypoglycaemia if it occurs, e.g. sugar sachets or jelly beans
carry emergency food rations in case of a delay, e.g. dried fruit, biscuits or muesli bars
keep Amaryl readily available
If you become sick with a cold, fever or flu, it is very important to continue taking Amaryl, even if you feel unable to eat
your normal meal. If you have trouble eating solid foods, use sugar-sweetened drinks as a carbohydrate substitute or eat small
amounts of bland food.
Your diabetes educator or dietician can give you a list of food to use for sick days.
Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Amaryl.
Amaryl helps most people with diabetes, but it may have unwanted side effects in a few people.
All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment
if you get some of the side effects.
Ask your doctor or pharmacist to answer any questions you may have.
Tell your doctor or pharmacist if you notice any of the following and they worry you:
signs of hypoglycaemia, which may include weakness, trembling or shaking, sweating, light-headedness, headache, dizziness,
lack of concentration, tearfulness or crying, irritability, hunger and numbness around the lips and fingers
eye problems, including blurred or double vision
stomach upset including nausea (feeling sick) and vomiting
diarrhoea, abdominal pain or a feeling of fullness in the stomach
Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:
rash, sores, redness or itching of the skin, itchy hives-like rash or spots
symptoms of sunburn such as redness, itching, swelling or blistering which may occur more quickly than normal
bleeding or bruising more easily than normal, or reddish or purplish blotches under the skin
yellowing of the skin or eyes, also called jaundice
signs of frequent or worrying infections, such as fever, severe chills, sore throat or mouth ulcers
signs of anaemia, such as tiredness, being short of breath and looking pale.
Tell your doctor or pharmacist if you notice anything that is making you feel unwell.
Other side effects not listed above may occur in some people.
Do not be alarmed by this list of possible side effects.
You may not experience any of them.
After using Amaryl
Keep your tablets in the blister pack until it is time to take them.
If you take the tablets out of the blister pack they may not keep well.
Keep your tablets in a cool dry place where the temperature stays below 25°C.
Do not store Amaryl or any other medicine in the bathroom or near a sink. Do not leave it in the car on hot days or on window
Heat and dampness can destroy some medicines.
Keep it where children cannot reach it.
A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.
If your doctor tells you to stop using Amaryl or the tablets have passed their expiry date, ask your pharmacist what to do
with any that are left over.
What it looks like
Amaryl 1 mg tablets: pink oblong, scored tablets with “NMK” and the Hoechst logo on both sides.
Amaryl 2 mg tablets: green oblong, scored tablets with “NMM” and the Hoechst logo on both sides.
Amaryl 3 mg tablets: pale yellow oblong, scored tablets with “NMN” and the Hoechst logo on both sides.
Amaryl 4 mg tablets: light blue oblong, scored tablets with “NMO” and the Hoechst logo on both sides.
The tablets are packed in blister packs of 30 tablets.
sodium starch glycollate
In order to distinguish between the different tablet strengths, each strength contains different colourings. These are:
Amaryl 1 mg tablets – iron oxide red
Amaryl 2 mg tablets – iron oxide yellow and indigo carmine lake
Amaryl 3mg tablets – iron oxide yellow
Amaryl 4 mg tablets – indigo carmine lake
Amaryl is supplied in Australia by:
sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
This leaflet was prepared in August 2016.
Australian Registration Numbers:
Amaryl 1 mg: AUST R 57186
Amaryl 2 mg: AUST R 57189
Amaryl 3mg : AUST R 79334
Amaryl 4 mg: AUST R 57191
Glimepiride: Uses, Side Effects, Precautions, Dosage and More
Details on Glimepiride | www.healthura.com
GENERIC NAME: Glimepiride
COMMON BRAND: Amaryl
Uses | Side-Effects | Precautions | Interactions| Forms and Strengths | Dosage | FAQ’s
Glimepiride is a long-acting oral anti-diabetic prescription medicine belonging to a class of drugs known as sulfonylureas. This drug is used only in patients with type II diabetes. It can be used along with Insulin or other medicines to control the blood sugar levels better. Glimepiride acts by stimulating the pancreas to produce insulin and helps the body use insulin more efficiently.
What is Glimepiride used for?
Glimepiride is used along with a proper diet, exercise program, and sometimes with other medications, to control high blood sugar levels in people with type 2 diabetes. This medication helps to lower blood sugar in people who produce insulin naturally. This drug is not recommended to use in the treatment for type 1 diabetes (a condition in which the body does not produce insulin). 
The drug may also be used to lessen the risk of life-threatening complications such as kidney damage, nerve problems, blindness, loss of limbs, and sexual function issues that develop in type 2 diabetic patients.
How to use Glimepiride?
Glimepiride comes as a tablet to take it orally. It is taken once a day with breakfast or the first main meal of the day, as directed by your doctor. Follow all the instructions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. The dose of the drug is based on your medical condition and response to treatment.
Take this drug exactly as prescribed at around the same time every day, do not take more frequently or less of it or take it more than your doctor prescribed.
Follow your doctor’s instructions carefully, to lessen the risk of side effects; your doctor may direct you to start on a low dose of glimepiride and gradually increase your dose if needed. Ensure your doctor about your blood sugar level results, whether it is higher or lower than normal during your treatment.
This drug helps to control blood sugar levels but does not cure diabetes. Regularly take glimepiride even if you feel better. Do not stop taking this drug without informing your doctor.
What are the side effects of Glimepiride?
The most common side effects of this drug are low blood sugar (hypoglycemia), headache, nausea, dizziness, weakness, and unexplained weight gain. If any of these side effects remains or worsens, inform your doctor or pharmacist promptly.
Seek emergency medical assistance promptly if you notice any of these severe side effects like stomach/abdominal pain, yellowing eyes/skin, dark urine, unusual tiredness/weakness, easy bleeding/bruising, signs of infection (such as fever, persistent sore throat), unusual/sudden weight gain, mental/mood changes, seizures.
Hypersensitivity (allergic) reactions to this drug are infrequent. Still, it may cause severe allergic reactions, like anaphylaxis (symptoms like trouble breathing, swelling of your throat or tongue, hives, or difficulty swallowing), angioedema (symptoms like swelling of your skin, the layers under your skin, and your mucous membranes.
This drug sometimes causes hyperglycemia (high blood sugar) symptoms like thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, and fruity breath odor. If any of these symptoms occur, inform your doctor right away. Your dose of the drug may need to be increased.
This is not a full record of all possible side effects. If you notice any other effects not listed above, contact your doctor or pharmacist.
What are the precautions while using Glimepiride?
Tell your doctor or pharmacist about your medical history, mainly liver disease, thyroid disease, kidney disease, certain hormonal conditions (adrenal/pituitary insufficiency, syndrome of inappropriate secretion of antidiuretic hormone), hyponatremia (electrolyte imbalance).
Consult your doctor if you have a certain complication like fever, infection, injury, or surgery. It may require to change in your treatment plan or medications to control your blood sugar level.
You may observe drowsiness or dizziness, blurred vision due to extremely low or high blood sugar levels. Avoid using machinery, driving, or doing any other activity that requires alertness or clear vision until you can safely.
Restrict the use of alcohol with this drug as it increases your risk of low blood sugar. Older adults are more prone to the side effects of this drug, mainly low blood sugar.
This drug can cause hemolytic anemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency, use caution in patients with G6PD deficiency, and consider using a non-sulfonylurea alternative.
Pregnancy may induce or worsen diabetes. Discuss with your doctor for managing your high blood sugar level in pregnancy. Your doctor may change your diabetic treatment during your pregnancy (like diet and medications, including insulin). In pregnancy, this medication should be used only when the benefits outweigh the risk.
Breastfeeding while using this medication is not recommended as it is not clear whether this medication passes into breast milk. Consult your doctor before breastfeeding.
What are the drug interactions of Glimepiride?
Many drugs may affect your blood sugar levels, making it difficult to control. Before you start using this drug, tell your doctor about all the products you are using, including prescription and over-the-counter medications. Regularly monitor your blood sugar levels and share the results with your doctor. Inform your doctor right away if you have high or low blood sugar symptoms as it may require to adjust your diabetes medication, exercise program, or diet.
Beta-blocker drugs (like propranolol, metoprolol, glaucoma eye drops such as timolol) may prevent the fast/pounding heartbeat you generally feel when your blood sugar falls too low (hypoglycemia). Other symptoms of low blood sugar like hunger, dizziness, or sweating are unaffected by these drugs.
Read all the labels carefully on your medicines (like cough-and-cold products) as they may contain ingredients that could affect your blood sugar levels. Seek advice from your pharmacist about using those products safely.
What are the forms and strengths of Glimepiride?
Strengths: 1mg, 2mg, 4mg, 6mg, and 8mg
Form: Oral tablet
Strengths: 1mg, 2mg, and 4mg
What is the dosage of Glimepiride?
For Type 2 Diabetes Mellitus:
Adult (18 to 64 years):
Initial dose: 1 to 2mg orally once a day
Maintenance dose: Increase the dose by 1-2mg every 1-2 weeks based on your glycemic response.
Maximum dose: Not to exceed 8mg per day.
Use in monotherapy or, if the glycemic response to glimepiride is inadequate at the maximum dose, with insulin or metformin.
Renal impairment: Start with 1mg orally once a day, and if the required increase dose based on fasting blood glucose levels.
Hepatic impairment: start with 1mg orally once a day and if the required increase dose carefully. It is not recommended to use in severe hepatic impairment.
The patients who are at high risk for hypoglycemia(low blood sugar level), start with 1mg orally once a day and increase slowly.
Observe patients for 1-2 weeks when being transferred from long half-life sulfonylureas to glimepiride, as of potential for overlapping of hypoglycemic effects.
children (0 to 17 years):
The use of this drug in children is not recommended as the safety and efficacy of this drug are not established.
Geriatric (65 years and above):
Start with 1mg orally once a day and if required increase dos at weekly intervals to avoid hypoglycemia.
Prolonged hypoglycemia reported with the use of this drug, increase the dose slowly; monitor closely for hypoglycemic or hyperglycemic symptoms.
Most Commonly Asked Questions/faqs:
Is Glimepiride the same as Metformin?
Glimepiride and Metformin are both used for the treatment of type-2 diabetes. However, the significant difference is in their structures; and glimepiride is a long-acting oral anti-diabetic prescription drug, belonging to a class known as sulfonylureas, whereas metformin is a prescription medicine belonging to a class known as biguanides. Glimepiride is usually prescribed once a day.
What does Glimepiride do to your body?
Like all sulfonylureas, glimepiride also works as an insulin secretagogue (stimulates insulin secretion). It reduces blood sugar levels by stimulating insulin release by pancreatic beta cells and by inducing increased activity of intracellular insulin receptors. Glimepiride is used with diet and exercise and sometimes with other medications to treat type 2 diabetes.
What are the side effects of taking Glimepiride?
The most common side effects of glimepiride are hypoglycemia (low blood sugar), headache, nausea, dizziness, weakness, and unexplained weight gain.
What are the symptoms of hypoglycemia?
Some of the hypoglycemia symptoms are trembling or shaking, nervousness or anxiety, irritability, sweating, lightheadedness or dizziness, headache, increase in heart rate or palpitations, intense hunger, fatigue, or tiredness.
How do you take Glimepiride?
Glimepiride is taken exactly as your doctor has recommended. It is usually prescribed once a day and is taken shortly before or with your first meal of the day (usually breakfast).
Can I drink alcohol while taking Glimepiride?
Taking alcohol while using glimepiride can worsen the side effects and may lead to flushing, headache, blurred vision, chest pain, nausea, vomiting, weakness, confusion, sweating, choking, difficulty breathing, and anxiety.
Does Glimepiride cause weight gain?
Yes, glimepiride is known to cause weight gain in some patients. It is not recommended for people under 18 years old because it may affect body weight and cause low blood sugar. If your blood sugar level is under good control, you should not stop or change your medication without discussing your condition with your doctor. 
Is Glimepiride long-acting?
Yes, glimepiride is a long-acting oral anti-diabetic prescription medicine belonging to a class of drugs known as sulfonylureas. It is also classified as the first third-generation sulfonylurea or as a second-generation sulfonylurea.
How long does Glimepiride work in the body?
Glimepiride is a long-acting oral anti-diabetic drug, and this means there is no sudden peak of the concentration of this drug in the blood, and it will maintain the blood glucose level even for 24 hours.
How does Glimepiride work in the body?
Glimepiride works as an insulin secretagogue (stimulates insulin secretion). It lowers the body’s blood sugar level by stimulating the release of insulin by pancreatic beta cells and causes increased activity of intracellular insulin receptors. Glimepiride is used along with proper diet and exercise and sometimes in combination with other medications to treat type 2 diabetes.
What does Glimepiride do for diabetes?
Glimepiride is prescribed along with a proper diet and exercise to control high blood sugar in people with type 2 diabetes. It is also prescribed, along with other diabetes medications. Controlling high blood sugar levels helps prevent kidney damage, nerve problems, blindness, loss of limbs after infection, and sexual function problems.
Are Glipizide and Glimepiride the same?
Glipizide/Glimepiride/Glyburide (Sulfonylureas) works by a similar mechanism of action by stimulating the pancreas to release insulin. Sometimes, the pancreas releases more insulin than needed. However, glimepiride appears to reduce blood glucose more rapidly than glipizide over the first few treatment weeks.
Is Glyburide and Glimepiride the same?
Glipizide/Glimepiride/Glyburide (Sulfonylureas) works by a similar mechanism of action by stimulating the pancreas to release insulin. Sometimes, the pancreas releases more insulin than needed. The pancreas’ increase in insulin production tends to act as a more powerful courier to “muscle” glucose into the cells, achieving lower blood sugar levels.
Is Glimepiride safe for kidneys?
Sulfonylureas like Glipizide/Glimepiride/Glyburide are removed from your body by the kidneys. If you have any kidney problems, your doctor may prescribe you some other diabetes drug as glimepiride may build up in your body and can cause low blood sugar.
Cholesterol Lowering Drugs
Gastroesophageal Reflux Disease
High Blood Pressure
Proton Pump Inhibitors
selective serotonin reuptake inhibitors
type 2 diabetes
Glimepiride – Uses, Side Effects, Substitutes, Composition And More
This medicine is used for the management of noninsulin-dependent diabetes mellitus (type 2) as an adjunct to diet and exercise to lower blood glucose. Used in combination with insulin to lower blood glucose in patients whose hyperglycemia cannot be controlled by diet and exercise in conjunction with an oral hypoglycemic agent.
Glimepiride is a drug that is used on treating patients suffering from type 2 Diabetes, who can’t control blood sugar levels through diet and exercise alone. Hence this drug is used to enhance the positive effects of diet and exercise with respect to blood sugar.
It is also used in combination with other antidiabetic medicines. It is a type of sulfonylurea antidiabetic medicine, that helps the pancreas in releasing insulin thus helping reduce the blood sugar level. It belongs to a class of drugs known as sulfonylureas.
Glimepiride is a type of sulfonylurea antidiabetic medicine which helps the pancreas in releasing insulin thus helping reduce the blood sugar level. It belongs to a class of drugs known as sulfonylureas. Glimepiride is available in oral tablet form.
Before starting a course of the medication, there are certain precautions that need to be taken. Firstly, any form of allergy must be mentioned to the consulting doctor. Also, if you have any history of kidney or liver diseases, it should be mentioned to the doctor.
Glimepiride makes the skin much more sensitive to the sun. Hence, if you are using this medication, use sunscreen to avoid skin problems. Limit the intake of alcohol during medication. Also, inform the doctor if you are currently using any prescribed drugs or diet supplement.
This drug shouldn’t be used by pregnant women. If you had a surgery recently, it is advisable not to take this medicine. The starting dose for Glimepiride is a 1mg tablet once every day. Glimepiride should be stored at a temperature between 20 to 25 degree Celcius. It should be kept away from heat, moisture and direct sunlight. Keep the drug away from the reach of the children and pets.
Information given here is based on the salt content of the medicine. Uses and effects of the medicine may vary from person to person. It is advisable to consult a Diabetologist before using this medicine.
Glimepiride – Oral | HealthLink BC
Common Brand Name(s): Amaryl
Important: How To Use This Information
This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Glimepiride is used with a proper diet and exercise program to control high blood sugar in people with type 2 diabetes. It may also be used with other diabetes medications. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke. Glimepiride belongs to the class of drugs known as sulfonylureas. It lowers blood sugar by causing the release of your body’s natural insulin.
How To Use
Read the Patient Information Leaflet if available from your pharmacist before you start taking glimepiride and each time you get a refill. If you have any questions, ask your doctor or pharmacist.
Take this medication by mouth with breakfast or the first main meal of the day, as directed by your doctor, usually once daily. The dosage is based on your medical condition and response to treatment.
Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.
To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor’s instructions carefully.
If you are already taking another diabetes drug (such as chlorpropamide), follow your doctor’s directions carefully for stopping the old drug and starting glimepiride.
Colesevelam can decrease the absorption of glimepiride. If you are taking colesevelam, take glimepiride at least 4 hours before taking colesevelam.
Tell your doctor if your condition does not improve or if it worsens (your blood sugar is too high or too low).
Nausea and upset stomach may occur. If either of these effects persists or worsens, tell your doctor or pharmacist promptly.
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Tell your doctor right away if you have any serious side effects, including:
- yellowing eyes/skin
- stomach/abdominal pain
- dark urine
- unusual tiredness/weakness
- easy bleeding/bruising
- signs of infection (such as fever, persistent sore throat)
- mental/mood changes
- unusual/sudden weight gain
This medication can cause low blood sugar (hypoglycemia). This may occur if you do not consume enough calories from food or if you do unusually heavy exercise. Symptoms of low blood sugar include sudden sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, or tingling hands/feet. It is a good habit to carry glucose tablets or gel to treat low blood sugar. If you don’t have these reliable forms of glucose, rapidly raise your blood sugar by eating a quick source of sugar such as table sugar, honey, or candy, or drink fruit juice or non-diet soda. Tell your doctor right away about the reaction and the use of this product. To help prevent low blood sugar, eat meals on a regular schedule, and do not skip meals. Check with your doctor or pharmacist to find out what you should do if you miss a meal.
Symptoms of high blood sugar (hyperglycemia) include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, and fruity breath odor. If these symptoms occur, tell your doctor right away. Your medication dosage may need to be increased.
A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including:
- itching/swelling (especially of the face/tongue/throat)
- severe dizziness
- trouble breathing
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
In the US –
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.
In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
Before taking glimepiride, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.
Before using this medication, tell your doctor or pharmacist your medical history, especially of:
- liver disease
- kidney disease
- thyroid disease
- certain hormonal conditions (adrenal/pituitary insufficiency, syndrome of inappropriate secretion of antidiuretic hormone-SIADH)
- electrolyte imbalance (hyponatremia)
You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely.
Limit alcohol while taking this medication because it can increase your risk of developing low blood sugar.
It may be harder to control your blood sugar when your body is stressed (such as due to fever, infection, injury, or surgery). Consult your doctor because this may require a change in your treatment plan, medications, or blood sugar testing.
This medication may make you more sensitive to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors. Tell your doctor right away if you get sunburned or have skin blisters/redness.
Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).
Older adults may be more sensitive to the side effects of this drug, especially low blood sugar.
During pregnancy, this medication should be used only when clearly needed. Pregnancy may cause or worsen diabetes. Discuss a plan with your doctor for managing your blood sugar while pregnant. Your doctor may substitute insulin for this drug during pregnancy. If glimepiride is used, it may be switched to insulin at least 2 weeks before the expected delivery date because of glimepiride’s risk of causing low blood sugar in your newborn. Discuss the risks and benefits with your doctor.
It is unknown if this medication passes into breast milk. However, similar drugs pass into breast milk. Breast-feeding while using this medication is not recommended. Consult your doctor before breast-feeding.
See also How to Use section.
Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.
Many drugs can affect your blood sugar, making it harder to control. Before you start, stop, or change any medication, talk with your doctor or pharmacist about how the medication may affect your blood sugar. Check your blood sugar regularly as directed and share the results with your doctor. Tell your doctor right away if you have symptoms of high or low blood sugar. (See also Side Effects section.) Your doctor may need to adjust your diabetes medication, exercise program, or diet.
Beta-blocker medications (including metoprolol, propranolol, glaucoma eye drops such as timolol) may prevent the fast/pounding heartbeat you would usually feel when your blood sugar falls too low (hypoglycemia). Other symptoms of low blood sugar such as dizziness, hunger, or sweating are unaffected by these drugs.
Check the labels on all your medicines (such as cough-and-cold products) because they may contain ingredients that could affect your blood sugar. Ask your pharmacist about using those products safely.
If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: shakiness, fast heartbeat, sweating, loss of consciousness.
Do not share this medication with others.
Attend a diabetes education program to learn more about how to manage your diabetes with medications, diet, exercise, and regular medical exams.
Learn the symptoms of high and low blood sugar and how to treat low blood sugar. Check your blood sugar regularly as directed.
Keep all regular medical and laboratory appointments. Laboratory and/or medical tests (such as liver and kidney function tests, fasting blood glucose, hemoglobin A1c, complete blood counts) should be performed periodically to monitor your progress or check for side effects.
If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.
Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).
Sulfanilamide of the third generation glimepiride in the treatment of type 2 diabetes mellitus | Dreval A.V.
In the treatment of type 2 diabetes mellitus (DM), a fairly wide range of drugs is currently used (Table 1), among which glimepiride occupies a special place. Brief information about glimepiride is presented in table 2.
In the treatment of type 2 diabetes mellitus (DM), a fairly wide range of drugs is currently used (Table 1), among which glimepiride occupies a special place.Brief information about glimepiride is presented in table 2.
According to the algorithms of the American Diabetes Association / European Association for the Study of Diabetes and the International Diabetes Federation (Fig. 1), the choice of antidiabetic therapy depends on the current and target level of glycated hemoglobin (HbA1c). Initial treatment for T2DM usually includes a recommendation for lifestyle changes (as close as possible to the so-called “healthy”) and metformin. In case of ineffectiveness of the prescribed therapy, tableted antihyperglycemic drugs (TSSP) are combined and injections of an analogue / mimetic GLP-1 or insulin (usually with prolonged action) can also be added .Within the framework of this algorithm, second- and third-generation sulfonylurea derivatives (SUDs) are preferable to the first generation, due to the lower risk of hypoglycemia [3,4].
Long-acting first-generation sulfonylurea derivatives (PSUs), such as chlorpropamide, frequently caused hypoglycemia and other side effects, including fluid retention, hyponatremia, and their efficacy was unpredictably altered when combined with a variety of drugs and alcohol .Second-generation PSMs (gliclazide, glipizide, glibenclamide) and third-generation PSMs (glimepiride), on the contrary, are usually safer and less likely to cause hypoglycemia. For example, in a study comparing glipizide with first-generation SCI, hypoglycemia during treatment with glipizide was 23% less common .
Glimepiride was first used in clinical practice in Sweden  and was registered by the FDA for use in the United States in 1995 . It is currently used in more than 60 countries around the world.It is packaged at a dosage of 1, 2, 3 and 4 mg / tab. [eight]. The main advantages of glimepiride in comparison with other PSMs are fast and complete absorption [6,9] and the ability to use it once a day . The risk of developing hypoglycemia with glimepiride is relatively low. A large prospective population-based study reported that the incidence of severe hypoglycemia with this drug was 6.5 times lower than with glyburide . When using glimepiride, a less pronounced increase in body weight was also observed than when using other PSM, with a comparable glucose-lowering effect in patients with type 2 diabetes [12,13].At the same time, like other PSMs, there is a risk of hypoglycemia during treatment with glimepiride, and rare side effects from hematological blood parameters may be observed . In addition, glimepiride increases the insulin sensitivity of insulin-dependent tissues [7,15,16].
The molecular formula of glimepiride is C24h44N4O5S, the molecular weight is 490.6 g / mol, and its chemical structure is shown in Figure 2.
The International Union of Pure and Applied Chemistry (IUPAC) named it 4-ethyl-3-methyl-N– [2– [4 – [(4-methylcyclohexyl) carbamolsulfamoyl] phenyl] ethyl] –5 – oxo – 2H – pyrrole – 1 –Carboxamide .It is practically insoluble in water [6,7]. PSMs have the same central structure, and their differences are noted in two positions: in the para-position of the benzene ring and in the urea site .
On the surface of a b-cell producing insulin, glimepiride binds to the sulfanilamide receptor, which is associated with the transmembrane ATP-dependent potassium channel . The specific center of its interaction with the sulfanilamide receptor is a 65-kDa protein site, which differs from that with which most other PSMs bind.Binding of PSM to one of the receptor sites blocks binding to any other sites of sulfanilamide receptors , and thus allosteric inhibition of the action of sulfonamides is manifested. That is why the combination of various sulfonamide preparations is devoid of any clinical sense.
When PSM binds to the receptor, the b-cell’s ATP-dependent potassium channel is closed, which blocks the entry of potassium from the extracellular space into the b-cell, and this, in turn, causes depolarization of the cell membrane.In response, voltage-gated calcium channels of the cell membrane open, calcium enters the b-cell, its concentration in the b-cell increases, which stimulates insulin secretion .
Compared with glyburide, glimepiride has 2–3 times less affinity for the b-cell sulfanilamide receptor, but 2.5–3 times higher frequency of association with the receptor and 8–9 times higher frequency of dissociation with it . As a result, the sulfanilamide receptor is blocked by glimepiride to a lesser extent than other PSMs, which is believed to be the reason for the low risk of hypoglycemia during treatment with glimepiride [2,11].
After oral administration, glimepiride is rapidly absorbed, and its bioavailability reaches 100% [5,8], and it is practically not affected by food intake [6,22]. In humans, 99% of glimepiride circulates in the blood in a form associated with plasma proteins, mainly with albumin [20,21]. It is metabolized in the liver  and is not excreted unchanged in the urine , in contrast to the first generation PSM, which are excreted unchanged, mainly by the kidneys . In the liver, glimepiride is converted by the CYP4502C9 enzyme first to the M1 metabolite.Then cytosolic enzymes convert M1 into its carboxyl derivative – M2 . Animal studies show that M1 has 30% activity of the parent substance, while M2 is practically devoid of physiological effect . Most of both metabolites are excreted in the urine (60%) , and the remainder is excreted in the feces.
After administration, the maximum concentration of glimepiride is reached after 2–3 hours , and it linearly depends on the dose of the drug in the range of 1–8 mg . The half-life (t1 / 2) with a single dose is 5 hours and increases to 9 hours with repeated administration .But at the same time, the constant intake of the drug is not accompanied by its cumulation [6,20]. When glimepiride is taken twice a day, two peaks of its concentration in serum (Cmax) are observed, and once a day – one peak. The frequency of administration of glimepiride does not affect the time to reach the maximum concentration of the drug in the blood (Tmax). The value of Cmax with a single dose of the drug is higher than with a double dose, although this does not affect the dose of the drug entering the systemic circulation (AUC) .
There were no significant differences in Cmax, Tmax, elimination half-life or AUC depending on obesity in T2DM patients.However, differences in the pharmacokinetics of metabolites M1 and M2 were revealed — higher in T2DM in obese people, but these differences have no clinical significance .
The predominantly hepatic metabolism of glimepiride allows its use in persons with minor renal impairment; however, since it is a stimulant of insulin secretion, insulin clearance will be slowed down by impaired renal function, which increases the risk of hypoglycemia.
Rosenkranz et al. studied the effect of glimepiride in patients with impaired renal function .In patients with creatinine clearance (CrCl) <50%, Cmax, t1 / 2, and the mean time of action for glimepiride did not change. Cmax and t1 / 2 for M1 and M2 were increased. The relative total clearance and volume of distribution of glimepiride increased at CrCl <50%, and the changes were proportional to the degree of renal impairment. In most patients with CRF, a dose of 1–4 mg glimepiride was sufficient to achieve target glycemic values. Only 1 mg / day of glimepiride was needed in patients with severe renal impairment (glomerular filtration <22 ml / min) .It is believed that the increase in the relative clearance of the drug in chronic renal failure is associated with a violation of its binding to proteins - with kidney damage, more glimepiride is in the unbound state . Taking into account the presented results, when using glimepiride in patients with chronic renal failure and creatinine clearance <22 ml / min, treatment should be started with its minimum dose (1 mg), carefully monitoring the effect of the drug .
Due to the fact that the hepatic metabolism of the drug is provided by the CYP4502C9 enzyme, with different variants of the CYP2C9 genotype, specific effects may develop.In particular, in individuals with the CYP2C9 * 1 / * 3 genotype, the violation of glimepiride metabolism is manifested by an increase in AUC, although no changes in Cmax were observed . In these cases, the initial dose of the drug should be low or medium. The antifungal drug fluconazole inhibits the above enzyme and, accordingly, increases the AUC for glimepiride . At the same time, liver diseases do not affect the pharmacokinetics of glimepiride , however, given the small number of patients with liver disease (11 people), caution should be exercised when using the drug in patients with this pathology [7,14,24].
Glimepiride enhances both the first and second phases of insulin secretion, both in normal blood glucose levels and in hyperglycemia . The maximum activity in reducing blood glucose levels is achieved in 2-3 hours, and the glucose-lowering effect after a single administration can last up to 24 hours . The maximum level of insulin and C-peptide in the blood is observed 2 hours after ingestion of glimepiride, and it enhances the stimulation of insulin secretion caused by an increase in glycemia after meals [7,26].Both under conditions of euglycemia and hyperglycemia, there is a linear relationship between the concentration of glimepiride in the blood and insulin secretion [7,24].
Glimepiride increases the sensitivity of insulin-dependent tissues to insulin both in vivo and in vitro . This may be due to the stimulation of the activity of the glucose transport protein GLUT4 [7,27,28].
Glimepiride inhibits lipolysis and stimulates the accumulation of triglycerides in rat adipocytes, acting through phosphodiesterase and 5′-nucleotidase.These enzymes move from specialized areas of the cell membrane to intracellular lipid droplets and hydrolyze cAMP in response to the action of glimepiride .
Despite the fact that glimepiride has an affinity for ATP-dependent potassium channels on cardiomyocytes , it does not violate the so-called ischemic preconditioning (unlike some other PSM). The essence of ischemic preconditioning is that short-term myocardial ischemia, which does not cause myocardial infarction, reduces the risk of myocardial infarction during prolonged ischemia.Since PSM suppress the opening of ATP-dependent potassium channels, they can disrupt this adaptive response of the myocardium, which develops with the participation of these channels. This distinctive quality of glimepiride may be due to the fact that, unlike other PSMs, it affects the activity of ATP-dependent potassium channels on the sarcolemma, but not the activity of mitochondrial channels in cardiomyocytes [31, 48]. Despite the fact that the clinical significance of ischemic preconditioning in humans has not been studied , it can be assumed from the obtained experimental data that glimepiride has an advantage over other SCIs in patients with an increased risk of heart attack.
The effectiveness of glimepiride
The dose-response relationship for glimepiride in the dosage range of 1, 4 or 8 mg / day was studied in a randomized study of 304 patients with T2DM. At all doses of glimepiride, there was a significant decrease in fasting blood glucose (GN) and 2 hours after a meal (GLP), as well as HbA1c (p <0.001). Specifically, GN levels decreased by 2.4, 3.8, and 4.1 mmol / L with 1, 4, and 8 mg of glimepiride, respectively; GLP decreased by 3.5, 5.1 and 5.0 mmol / L, respectively; HbA1c levels decreased by 1.2, 1.8 and 1.9%, respectively .
Rosenstock et al. presented the results of a randomized, double-blind, multicenter study involving 416 patients with T2DM receiving SCI. Patients were prescribed glimepiride in four dosages: 4 and 8 mg 2 times a day and 8 and 16 mg / day. within 14 weeks. In patients receiving placebo, the level of GN increased slightly from 13.0 mmol / L at the beginning of the study to 14.5 mmol / L at the end, and with all glimepiride treatment regimens, on the contrary, decreased by 3.9-5.7 mmol / l. Compared with placebo, glimepiride also reduced GLP levels by 5.6–6.6 mmol / L.Within 2 hours after a meal, insulin and C-peptide levels increased in patients receiving glimepiride. The HbA1c level increased in the placebo group from 7.7% at the beginning of the study to 9.7% at the end (p <0.001), while in the glimepiride group it decreased from 8.0% to 7.5% (p≤0.001). There were no significant differences in hypoglycemic reactions between daily doses of 8 and 16 mg of glimepiride or between the variants of administration once a day or twice a day .
Another multicenter, randomized, placebo-controlled study involved 249 patients with type 2 diabetes, who studied the effectiveness of a 12-week course of treatment with 1-8 mg of glimepiride .The use of glimepiride led to a decrease in the average values of GN by 2.5 mmol / L, GLP by 4.0 mmol / L and HbA1c by 1.4% more than in the placebo group (p <0.001). The final HbA1c value of ≤ 7.2% was achieved in 69% of patients receiving glimepiride, and only in 32% of patients in the placebo group. In patients receiving glimepiride, stimulation of insulin and C-peptide secretion in response to food intake was observed, while the increase in insulinemia was insignificant on an empty stomach.
Similar data were obtained by Sonnenberg et al.in a 15-week crossover study of 106 patients with T2DM who were prescribed glimepiride and the choice of the initial dose of which (3 mg twice a day or 6 mg once a day for 4 weeks) was carried out at random. Patients were transferred every 4 weeks from one treatment option to another. The average daily glycemic level decreased comparable both when the drug was prescribed 2 times a day and once a day. Plasma insulin and C-peptide levels increased significantly at the peak of postprandial glycemia, but not on an empty stomach .
So, summarizing the above studies, we can draw the following conclusions regarding glimepiride monotherapy in comparison with placebo:
– glimepiride effectively reduces blood glucose levels both on an empty stomach and after a meal, and regardless of the frequency of taking the drug – once or twice a day;
– glimepiride increases insulin secretion in response to food intake and has practically no effect on the fasting level of insulinemia;
– treatment with glimepiride makes it possible to achieve the target HbA1c values recommended by the ADA / EASD / IDF in a significant proportion of patients with type 2 diabetes.
Attorese et al. compared the quality and nature of differences between 23 generic drugs on the market with Amaryl (all 2 mg) under stress conditions . Unpacked samples were stored at 60 ° C for 21 days to simulate temperature stress (accelerated aging model). Samples were analyzed under normal conditions (day 0), on days 7 and 21 for active ingredient content, impurity levels and residual solvent levels (under normal conditions only) and dissolution profile; the results were compared with those of Amaril.Overall, 74% (17 out of 23) of generic drugs did not meet quality and performance when compared with Amaril. This study showed that the vast majority of generic glimepiride products are of reduced quality and altered performance compared to the original product.
Glimepiride and other PSM
Dills and Schneider presented the results of a multicenter, randomized, double-blind study that examined the efficacy of glimepiride monotherapy versus glyburide monotherapy in 577 patients with T2DM .After 1 year of treatment, there was no significant difference in GN, GLP, or HA1c between the two groups (glimepiride versus glyburide). However, the incidence of hypoglycemia was lower in patients treated with glimepiride (1.7% versus 5.0%; p = 0.015).
Similar data were presented by Draeger et al., Describing a multicenter prospective double-blind study in patients with type 2 diabetes, which also compared the efficacy of glimepiride (n = 524) and glyburide (n = 520) . Glimepiride (1–8 mg once daily) has been shown to provide the same metabolic control as glyburide (2.5–20 mg / day), but glimepiride was less likely to cause episodes of hypoglycemia (105 versus 150).At the same time, during the treatment with glimepiride, there was a significantly lower increase in insulinemia (p = 0.04) and blood C-peptide (p = 0.03) on an empty stomach than in the treatment with glyburide. This partly explains the lower incidence of hypoglycemia in patients receiving glimepiride.
Glimepiride in combination
with other oral preparations
Charpentier et al. investigated the effectiveness of combination therapy with metformin and glimepiride in 372 patients with T2DM with initially ineffective metformin monotherapy.Three groups were formed in the study: monotherapy with metformin (M), monotherapy with glimepiride (G), and a combination of metformin and glimepiride (M + G). As a result, the combination of glimepiride and metformin was significantly more effective than monotherapy with each of the drugs:
• change in GN compared with the outcome: group M = 0.8 ± 0.4 mmol / l; group G = 0.7 ± 0.3 mmol / l; group M + G = –2.4 ± 0.2 mmol / l;
• change in GLP compared with the outcome: group M = 1.1 ± 0.8 mmol / l; group G = 0.3 ± 0.5 mmol / l; group M + G = –2.6 ± 0.3 mmol / l;
• change in HbA1c compared with the outcome: group M = 0.07 ± 0.14%; group G = 0.27 ± 0.09%; group M + G = –0.74 ± 0.08%.
McCluskey et al. presented the results of a multicenter, double-blind, placebo-controlled study of the hypoglycemic efficacy of rosiglitazone plus glimepiride versus rosiglitazone plus placebo. It was found that in the glimepiride group, the achievement of the target HbA1c level <7% occurred more often (60.0% versus 14.3%; p <0.006). Also, no significant differences were found between treatment groups in terms of frequency or type of adverse events (glimepiride and rosiglitazone versus placebo and rosiglitazone), and there were no episodes of severe hypoglycemia in either group during treatment .
Umpierrez et al.  presented the results of a randomized study of 203 patients with T2DM with poorly controlled glycemia, who were prescribed a fixed dose of metformin in combination with a modified dose of glimepiride or pioglitazone. Titration of the doses of glimepiride / pioglitazone to the maximum was performed within 26 weeks. In both treatment groups, there was a comparable and significant decrease in the mean values of HbA1c (p = 0.0001) and GN (p <0.05) compared to baseline levels.Combination therapy metformin + glimepiride led to a faster than metformin + pioglitazone decrease in HbA1c level (p <0.05) and achievement of HbA1c level ≤7% (median 80–90 days versus 140–150 days, p = 0.024). As a result, health care costs for combined treatment with metformin + glimepiride are lower than metformin + pioglitazone. The levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) at the end of the study were significantly higher in patients receiving pioglitazone (p <0.05).High-density lipoprotein cholesterol (HDL-C) levels increased with pioglitazone and decreased with glimepiride (p = 0.0001).
Glimepiride and secondary resistance to PSM
In our study, we found a phenomenon called “secondary pseudo-resistance to SCI”, eliminated by the administration of glimepiride (Amaryl) . As you know, a decrease in the glucose-lowering effect of PSM after 5–15 years of effective treatment is called secondary resistance to PSM – in contrast to the primary one, which is observed from the first prescription of PSM.But since SCIs cause hypoglycemia, we assumed that diabetes decompensation in some patients receiving SCIs may be caused by latent hypoglycemia (usually nocturnal), in response to which counterinsulin hormones are secreted, which causes diabetes decompensation. An increase in the dose of PSM in response to decompensation aggravates latent hypoglycemia, and diabetes is increasingly decompensated. That is, a kind of “looping” phenomenon (Somoji syndrome) develops in patients with T2DM on the background of SCI. Since glimepiride has the lowest risk of hypoglycemia among SCIs, we assumed that in a number of patients with secondary resistance to SCIs, replacing the previously prescribed SCI with glimepiride can restore T2DM compensation if the secondary resistance is false.
Our study involved 20 patients with T2DM. The observation period was 3 months. Inclusion criteria for the study: age over 40 years, diabetes duration more than 3 months, HbA1c level> 6.5%, fasting plasma glucose more than 7.8 mmol / L. Before enrollment in the study, patients received 1st or 2nd generation PSM in submaximal and maximum doses. Patients were prescribed Amaryl in an initial dose of 1 mg once a day immediately before breakfast, regardless of the dose of other tableted antihyperglycemic drugs taken before.According to the results of fasting glycemia, the dose of the drug was adjusted once every 2 weeks: with fasting glycemia less than or equal to 6.8 mmol / l, the dose of Amaril did not change (in the absence of hypoglycemia), with fasting glycemia more than 6.8 mmol / l, the dose of Amaril increased by 1 mg / day The maximum daily dose of Amaril was 8 mg.
During the observation period, HbA1c decreased on average by 2.2%, and glycemia – by 1.8 mmol / L, which indicates a significant improvement in the compensation of carbohydrate metabolism in patients included in the study.It should be noted that in 7 patients (35%) who had previously received glibenclamide at a dose close to the maximum (15-20 mg / day), a significant improvement in carbohydrate metabolism occurred while taking Amaril at a dose not exceeding half the maximum (3-4 mg). This observation, to a certain extent, confirms the above assumption about the possibility of the development of the “looping” syndrome on the SCM, and glimepiride can be considered as the drug of choice for eliminating this phenomenon.
Glimepiride in combination with insulin
Glimepiride is the only FDA approved SCM for combination therapy with insulin, which has been studied in a number of studies [41–45].
In one multicenter study  conducted in overweight patients with type 2 diabetes, aged 45–70 years with poorly controlled SCI monotherapy, it was shown that the combination of glimepiride with one evening injection of mixed insulin 70/30 (NPH + simple insulin) provided as effective in controlling blood glucose as the more complex multi-injection regimen without the use of oral medications.
Another multicenter, double-blind, randomized study  involved 208 patients with T2DM, in whom SCM monotherapy did not achieve the target blood glucose control.Patients were randomly assigned to one of two treatment regimens: one evening injection of mixed insulin 70/30 plus glimepiride or one injection per day of mixed insulin 70/30. GN targets were achieved in both groups, but faster with combination therapy (p <0.001 by week 2). At the same time, with combined therapy, the need for insulin was 40% lower (p <0.001), that is, glimepiride reduced the total daily dose of insulin in the studied population of patients with type 2 diabetes.
Kabadi et al.suggest that glimepiride reduces the need for insulin to a greater extent than other PSMs (tolazamide, glyburide, or glipizide) .
Fritsche et al. conducted a controlled randomized study of 695 patients with type 2 diabetes, which examined the efficacy and safety of taking 3 mg glimepiride in combination with morning or evening administration of insulin glargine (Lantus) or evening administration of NPH insulin. The insulin dose was titrated according to a special scheme, in which the target GN level was ≤ 5.5 mmol / L.The HbA1c level decreased by 1.24% in the group of patients who received Lantus in the morning, by 0.96% in those who received Lantus in the evening, and by 0.84% in those who received NPH in the evening. HbA1c scores were better with morning than evening Lantus injections (p = 0.008) or evening NPH insulin injections (p = 0.001). By the end of the study, the level of GN had improved from baseline equally in all groups. Nocturnal hypoglycemia was less common with both morning (17%) and evening Lantus insulin injections (23%), compared with evening NPH insulin injections (38%) (p <0.001).Thus, in T2DM patients, the risk of nocturnal hypoglycemia is lower when glimepiride is administered in combination with Lantus than with NPH insulin .
The absence of weight gain is an important indicator of the quality of drug treatment for patients with T2DM, since the main pathogenetic factor of T2DM, insulin resistance, causes obesity. In this respect, glimepiride has a significant advantage over other PSMs, insulin and pioglitazone, since, unlike them, it does not cause weight gain against the background of effective glycemic control .
In one study lasting up to 12 months, there was no significant weight gain in patients with type 2 diabetes treated with glimepiride , and in another 8-week study against the background of treatment with glimepiride, weight in patients with type 2 diabetes even decreased (by 1–2 kg), especially with severe obesity .
In a study  over 12 months, the effect of glimepiride and glyburide on body weight was compared in 520 outpatients with type 2 diabetes. It turned out that at the end of the study, the average body weight loss and decrease in body mass index relative to baseline were higher in the glimepiride group (–2.0 ± 4 kg / –0.7 ± 1.4 kg / m2) than in the group glyburide (–0.58 ± 3.7 kg / –0.2 ± 1.3 kg / m2) (p <0001) .
Despite the fact that the published data on the safety and tolerability of glimepiride do not exceed 2–3 years , they are numerous and include more than 5 thousand patients with T2DM. In placebo-controlled studies, most of the adverse events associated with glimepiride occurred in less than 2% of patients with type 2 diabetes, and these were hypoglycemia, dizziness, asthenia, headache, rash and nausea, and such reactions from the gastrointestinal tract, such as vomiting, abdominal pain and diarrhea occurred in less than 1% of patients .These studies indicate that adverse events associated with glimepiride are not more common, and in some cases even less common, than with other PSMs.
The most important clinical adverse effect of glimepiride, like other SCIs, is hypoglycemia. Holstein et al. compared the incidence of severe hypoglycemia (eliminated by intravenous glucose injections or glucagon) in patients treated with glimepiride or glyburide. The results of this study showed that the total incidence of hypoglycemia with glimepiride was 6.5 times lower than with glyburide .
Reducing the risk of hypoglycemia is also especially important for people who play sports or exercise regularly. Massi – Benedetti et al. showed that physical activity in T2DM patients receiving glimepiride causes a statistically significant decrease in C-peptide and insulin levels compared with patients receiving glyburide. This observation suggests that during treatment with glimepiride, the physiological ability to suppress the secretion of endogenous insulin is retained, which may explain the decrease in the incidence of hypoglycemia during and after exercise in patients receiving glimepiride .
The risk of developing hypoglycemia is also influenced by such factors as old age, concomitant diseases of the kidneys and / or cardiovascular system . Combination therapy with glimepiride with other oral hypoglycemic drugs may increase the risk of hypoglycemia .
Other undesirable serious effects of glimepiride include rare hematologic side effects such as leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, and pancytopenia .With the use of PSM, including glimepiride, the development of a syndrome of inappropriate antidiuretic hormone secretion was reported: it is believed that due to an increase in the action of antidiuretic hormone and / or stimulation of its secretion .
Thus, glimepiride, the third generation PSM, is a highly effective antihyperglycemic drug for the treatment of T2DM, which can be used as monotherapy (once a day) or in combination with other antihyperglycemic drugs of the non-sulfanilamide group, including insulin.Glimepiride effectively reduces GN, GLP and HbA1c levels and has a good safety profile.
Glimepiride does not affect body weight and poses a lower risk of hypoglycemia in type 2 diabetes than other stimulants of insulin secretion. The data obtained suggest that glimepiride may be safer than other PSMs in patients with cardiovascular diseases, since it does not block ischemic preconditioning. This is a very important circumstance, given that a large number of T2DM patients suffer from coronary artery disease.
1. Dreval A.V. “Treatment of diabetes mellitus”, M., Ed. EKSMO, 2010
2. Davis SN. The role of glimepiride in the effective management of type 2 diabetes. J Diabetes Complications 2004; 18 (6): 367–76
3. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes.Diabetes Care 2009; 32 (1): 193–203
4. International Diabetes Federation Clinical Guidelines Task Force. Global guidelines for type 2 diabetes. 2005. Available from: http://www.idf.org/Global_guideline. [Cited 20 June 2009]
5. Beisswenger PJ, Dias N, Beckman F. Evaluation of first – generation sulfonylureas and glipizide in non – insulin – dependent diabetes mellitus. Am J Med 1987; 83 (3A): 16-21
6. Massi – Benedetti M. Glimepiride in type 2 diabetes mellitus: a review of the worldwide therapeutic experience.Clin Ther 2003; 25 (3): 799-816
7. Campbell RK. Glimepiride: role of a new sulfonylurea in the treatment of type 2 diabetes mellitus. Ann Pharmacother 1998; 32 (10): 1044-52
8. Epocrates. Glimepiride. Drug Monographs 2009. Available from: https://online.epocrates.com/ noFrame / showPage.do? Method = drugs & MonographId = 381 & ActiveSectionId = 10. [Cited 21 June 2009]
9. Badian M, Korn A, Lehr KH, et al. Absolute bioavailability of glimepiride (Amaryl) after oral administration.Drug Metabol Drug Interact 1994; 11 (4): 331-9
10. Matsuki M, Matsuda M, Kohara K, et al. Pharmacokinetics and pharmacodynamics of glimepiride in type 2 diabetic patients: compared effects of once– versus twice – daily dosing. Endocr J 2007; 54 (4): 571-6
11. Holstein A, Plaschke A, Egberts EH. Lower incidence of severe hypoglycaemia in patients with type 2 diabetes treated with glimepiride versus glibenclamide. Diabetes Metab Res Rev 2001; 17 (6): 467-73
12. Bugos C, Austin M, Atherton T, Viereck C.Long – term treatment of type 2 diabetes mellitus with glimepiride is weight neutral: a meta – analysis. Diabetes Res Clin Pract 2000; 50 (Suppl 1): S47
13. Scholz G, Schneider K, Knirsch W, Becker G. Efficacy and tolerability of glimepiride in daily practice: a non-interventional observational cohort study. Clin Drug Invest 2001; 21 (9): 597-604
14. Sanofi – Aventis Canada, Inc. Product Monograph (Amaryl, glimepiride). 2009
15. Overkamp D, Volk A, Maerker E, et al. Acute effect of glimepiride on insulin – stimulated glucose metabolism in glucose – tolerant insulin – resistant offspring of patients with type 2 diabetes.Diabetes Care 2002; 25 (11): 2065-73
16. Muller G, Wied S, Straub J, Jung C. Coordinated regulation of esterification and lipolysis by palmitate, h3O2 and the anti-diabetic sulfonylurea drug, glimepiride, in rat adipocytes. Eur J Pharmacol 2008; 597 (1-3): 6-18
17. NCBI Pubchem Compound Database. National Center for Biotechnology Information. Glimepiride. 2009. Available from: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid= 3476 & loc = ec_rcs. [Cited 21 June 2009]
18.Kramer W, Muller G, Girbig F, et al. Differential interaction of glimepiride and glibenclamide with the beta – cell sulfonylurea receptor. II. Photoaffinity labeling of a 65 kDa protein by [3H] glimepiride. Biochim Biophys Acta 1994; 1191 (2): 278-90
19. Muller G, Hartz D, Punter J, et al. Differential interaction of glimepiride and glibenclamide with the beta – cell sulfonylurea receptor. I. Binding characteristics. Biochim Biophys Acta 1994; 1191 (2): 267-77
20. Shukla UA, Chi EM, Lehr KH.Glimepiride pharmacokinetics in obese versus non-obese diabetic patients. Ann Pharmacother 2004; 38 (1): 30-5
21. Rosenkranz B, Profozic V, Metelko Z, et al. Pharmacokinetics and safety of glimepiride at clinically effective doses in diabetic patients with renal impairment. Diabetologia 1996; 39 (12): 1617-24
22. Malerczyk V, Badian M, Korn A, et al. Dose linearity assessment of glimepiride (Amaryl) tablets in healthy volunteers. Drug Metabol Drug Interact 1994; 11 (4): 341-57
23.Niemi M, Cascorbi I, Timm R, et al. Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clin Pharmacol Ther 2002; 72: 326-32
24. Rosenkranz B. Pharmacokinetic basis for the safety of glimepiride in risk groups of NIDDM patients. Horm Metab Res 1996; 28 (9): 434-9
25. Korytkowski M, Thomas A, Reid L, et al. Glimepiride improves both first and second phases of insulin secretion in type 2 diabetes. Diabetes Care 2002; 25 (9): 1607-11
26.Rosenstock J, Samols E, Muchmore DB, Schneider J. Glimepiride, a new once – daily sulfonylurea. A double – blind placebo – controlled study of NIDDM patients. Glimepiride Study Group. Diabetes Care 1996; 19 (11): 1194-9
27. Muller G. The molecular mechanism of the insulin – mimetic / sensitizing activity of the antidiabetic sulfonylurea drug amaryl. Mol Med 2000; 6 (11): 907-33
28. Muller G, Satoh Y, Geisen K. Extrapancreatic effects of sulfonylureas – a comparison between glimepiride and conventional sulfonylureas.Diabetes Res Clin Pract 1995; 28 (Suppl): S115-37
29. Haupt A, Kausch C, Dahl D, et al. Effect of glimepiride on insulin – stimulated glycogen synthesis in cultured human skeletal muscle cells: a comparison to glibenclamide. Diabetes Care 2002; 25 (12): 2129–32
30. Song DK, Ashcroft FM. Glimepiride block of cloned beta – cell, cardiac and smooth muscle K (ATP) channels. Br J Pharmacol 2001; 133 (1): 193-9
31. Mocanu MM, Maddock HL, Baxter GF, et al. Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide.Circulation 2001; 103 (25): 3111-6
32. Goldberg RB, Holvey SM, Schneider J. A dose – response study of glimepiride in patients with NIDDM who have previously received sulfonylurea agents. The Glimepiride Protocol # 201 Study Group. Diabetes Care 1996; 19 (8): 849-56
33. Schade DS, Jovanovic L, Schneider J. A placebo – controlled, randomized study of glimepiride in patients with type 2 diabetes mellitus for whom diet therapy is unsuccessful. J Clin Pharmacol 1998; 38 (7): 636-41
34.Sonnenberg GE, Garg DC, Weidler DJ, et al. Short – term comparison of once versus twice – daily administration of glimepiride in patients with non – insulin – dependent diabetes mellitus. Ann Pharmacother 1997; 31 (6): 671-6
35. Attorrese G, Massi-Benedetti M. Quality and behavior generic versus amaryl under stress conditions. Diabetes Technology and Therapeutics 9 (3): 287-296, 2007
36. Dills DG, Schneider J. Clinical evaluation of glimepiride versus glyburide in NIDDM in a double – blind comparative study.Glimepiride / Glyburide Research Group. Horm Metab Res 1996; 28 (9): 426-9
37. Draeger KE, Wernicke-Panten K, Lomp HJ, et al. Long – term treatment of type 2 diabetic patients with the new oral antidiabetic agent glimepiride (amaryl): a double – blind comparison with glibenclamide. Horm Metab Res 1996; 28 (9): 419-25
38. McCluskey D, Touger MS, Melis R, Schleusener DS. Results of a randomized, double-blind, placebo-controlled study administering glimepiride to patients with type 2 diabetes mellitus inadequately controlled with rosiglitazone monotherapy.Clin Ther 2004; 26 (11): 1783–90
39. Umpierrez G, Issa M, Vlajnic A. Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial. Curr Med Res Opin 2006; 22 (4): 751-9
40. Dreval A.V., Misnikova I.V. Correction of pseudo-resistance to sulfonylurea preparations with Amaryl. Endocrinology problems. – 2000. – N 4. – P. 17-18
41. Garber AJ. Benefits of combination therapy of insulin and oral hypoglycemic agents.Arch Intern Med 2003; 163 (15): 1781–2
42. Riddle MC. Combined therapy with a sulfonylurea plus evening insulin: safe, reliable, and becoming routine. Horm Metab Res 1996; 28 (9): 430-3
43. Riddle MC, Schneider J. Beginning insulin treatment of obese patients with evening 70/30 insulin plus glimepiride versus insulin alone. Glimepiride Combination Group. Diabetes Care 1998; 21 (7): 1052-7
44. Kabadi MU, Kabadi UM. Efficacy of sulfonylureas with insulin in type 2 diabetes mellitus.Ann Pharmacother 2003; 37 (11): 1572-6
45. Fritsche A, Schweitzer MA, Haring HU. Glimepiride combined with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. A randomized, controlled trial. Ann Intern Med 2003; 138 (12): 952-9
46. Martin S, Kolb H, Beuth J, et al. Change in patients ’body weight after 12 months of treatment with glimepiride or glibenclamide in type 2 diabetes: a multicentre retrospective cohort study.Diabetologia 2003; 46 (12): 1611-7
47. Massi – Benedetti M, Herz M, Pfeiffer C. The effects of acute exercise on metabolic control in type II diabetic patients treated with glimepiride or glibenclamide. Horm Metab Res 1996; 28 (9): 451-5
48. Caulfield M, O’Brien K. Cardiovascular safety of oral antidiabetic agents: the insulin secretagogues. Clin Diabetes 2002; 20 (2): 81-4.
Combinations of insulin and oral hypoglycemic agents for people with type 2 diabetes mellitus on insulin treatment
Many type 2 sugar diet guides recommend that glycosylated hemoglobin A1c (HbA1c) levels be below 7%.Blood HbA1c levels represent or characterize glucose or glycemic control over a longer period of time (two to three months). As type 2 diabetes progresses, it becomes more difficult to achieve these levels through “lifestyle” modifications (diet and exercise) and oral hypoglycemic drugs alone. As a result, a significant number of people will need insulin therapy to improve glycemic control. Insulin therapy can be started only with insulin itself, which is called monotherapy (which means that oral glucose-lowering drugs will be canceled), or insulin therapy is carried out in combination with oral glucose-lowering drugs.In the former case, oral hypoglycemic agents may be added at a later stage if insulin monotherapy fails to achieve good HbA1c levels. Hypoglycemia and weight gain are the most common and well-known side effects of insulin therapy. Adding oral agents to insulin can reduce the required insulin dose and thus reduce these insulin-related side effects. However, there may be other side effects that are common with various oral glucose-lowering drugs.
To evaluate the effect of insulin monotherapy and the effects of the addition of oral hypoglycemic agents in people with type 2 diabetes mellitus already receiving insulin but not having adequate glycemic control.
It is unclear whether people with type 2 diabetes who are taking insulin as monotherapy but who do not achieve good glucose levels should continue to take insulin as monotherapy, or they may benefit from adding an oral antidiabetic agent to their insulin therapy.
Characteristics of research
All 37 included studies were randomized controlled trials (clinical studies in which people are randomly assigned to one of two or more treatment groups). Their duration ranged from 2 to 12 months. The total number of participants was 3227. Different types of insulin in monotherapy (long-acting for a single dose (per day) or intermediate-acting insulin, insulin pre-mixed for twice daily use, and short-acting insulin for repeated injections) were compared with different types of additional antidiabetic tablets: sulfonylureas (such as glibenclamide / glyburide), metformin, alpha-glucosidase inhibitors (such as acarbose), pioglitazone, and DPP-4 inhibitors (such as saxagliptin).
Adding oral agents to insulin monotherapy reduced HbA1c levels by 0.4% to 1%. Most combinations of oral antidiabetic agents with insulin resulted in a decrease in the required daily insulin dose, whereas the daily insulin dose had to be increased or remained stable in participants who continued insulin monotherapy. In studies reporting hypoglycemic episodes, severe events were rare, and episodes of mild to moderate hypoglycemia were observed in a similar number of participants when insulin monotherapy was compared with the addition of oral antidiabetic agents to insulin.However, most studies that added sulfonylureas to insulin reported more hypoglycemic episodes. Moreover, the addition of sulfonylureas to insulin resulted in additional weight gain of 0.4 kg to 1.9 kg compared to -0.8 kg to 2.1 kg in the insulin monotherapy group. Pioglitazone-insulin combination therapy caused an average weight gain of 3.8 kg compared with insulin monotherapy. The difference in the average weight gain when using the combination metformin – insulin compared with insulin monotherapy was 2.1 kg less, in favor of the combination therapy.Gastrointestinal side effects such as bloating and diarrhea have been reported most with metformin and alpha-glucosidase inhibitors. The addition of pioglitazone to insulin compared with insulin monotherapy resulted in an increased incidence of edema (fluid retention) and heart failure. Only one study evaluated participants’ satisfaction with treatment, and did not show any significant differences between the addition of glimepiride or metformin and glimepiride to insulin versus insulin monotherapy.None of the studies assessed all-cause mortality, diabetes-related morbidity, or health-related quality of life.
This evidence is current to November 2015.
Quality of evidence
Almost a third of the studies had 30 or fewer participants. Many studies turned out to be underpowered and therefore probably could not answer their own research question. This could mean that potentially important differences between the intervention and control groups were not found.Only five studies had follow-up for 12 months.
Amaryl m tab p / o film 2mg + 500mg 30 pcs
Lactic acidosis is a rare but severe (fatal if untreated) metabolic complication that results from the accumulation of metformin during treatment. Cases of lactic acidosis while taking metformin were observed mainly in patients with diabetes mellitus with severe renal failure.The incidence of lactic acidosis can and should be reduced by assessing the presence of other associated risk factors for lactic acidosis in patients, such as poorly controlled diabetes mellitus, ketoacidosis, prolonged fasting, heavy consumption of ethanol-containing drinks, liver failure, and conditions accompanied by tissue hypoxia. Lactic acidosis is characterized by acidotic dyspnea, abdominal pain, and hypothermia, followed by coma. Diagnostic laboratory manifestations are an increase in the concentration of lactate in the blood (> 5 mmol / L), a decrease in blood pH, a violation of the water-electrolyte balance with an increase in anion deficiency and the lactate / pyruvate ratio.In cases where metformin is the cause of lactic acidosis, the plasma concentration of metformin is usually> 5 μg / ml. If lactic acidosis is suspected, metformin should be discontinued immediately and the patient should be hospitalized immediately.
The reported incidence of lactic acidosis in metformin patients is very low (about 0.03 cases / 1000 patient-years). Reported cases occurred mainly in patients with diabetes mellitus with severe renal failure, including congenital kidney disease and renal hypoperfusion, often in the presence of numerous concomitant conditions requiring medical and / or surgical treatment.
The risk of developing lactic acidosis increases with the severity of renal dysfunction, as well as with age. The likelihood of lactic acidosis while taking metformin can be significantly reduced with regular monitoring of renal function and the use of the minimum effective dose of metformin. For the same reason, in conditions associated with hypoxemia or dehydration, it is necessary to avoid taking the drug Amaryl M.
Due to the fact that impaired liver function can significantly limit the excretion of lactate, the use of the drug Amaryl M should be avoided in patients with clinical or laboratory signs of diseases liver.
In addition, taking the drug Amaryl M should be temporarily discontinued before X-ray studies with intravascular administration of iodine-containing contrast agents and before surgical interventions. Reception of metformin should be interrupted for a period of 48 hours before and 48 hours after surgery using general anesthesia.
Often, lactic acidosis develops gradually and manifests itself only with nonspecific symptoms, such as feeling unwell, myalgia, respiratory problems, increasing drowsiness and nonspecific disorders of the gastrointestinal tract.With more pronounced acidosis, hypothermia, a decrease in blood pressure and resistant bradyarrhythmia may develop. Both the patient and the treating physician should be aware of how important these symptoms may be. The patient should be instructed to notify the physician immediately in the event of such symptoms. To clarify the diagnosis of lactic acidosis, it is necessary to determine the concentration of electrolytes and ketones in the blood, the concentration of glucose in the blood, the pH of the blood, the concentration of lactate and metformin in the blood.Plasma concentration of lactate in venous blood on an empty stomach, exceeding the upper limit of the norm, but below 5 mmol / L in patients taking metformin, does not necessarily indicate lactic acidosis; its increase can be explained by other mechanisms, such as poorly controlled diabetes mellitus or obesity, intense physical activity, or technical errors in blood sampling for analysis.
It should be assumed the presence of lactic acidosis in a patient with diabetes mellitus with metabolic acidosis in the absence of ketoacidosis (ketonuria and ketonemia).
Lactic acidosis is a critical condition requiring hospital treatment. If lactic acidosis is diagnosed, you should immediately stop taking Amaryl M and start general supportive measures. Metformin is removed from the blood by hemodialysis with a clearance of up to 170 ml / min, therefore, provided there are no hemodynamic disturbances, immediate hemodialysis is recommended to remove the accumulated metformin and lactate. Such measures often lead to a rapid disappearance of symptoms and recovery.
The effectiveness of any hypoglycemic therapy should be monitored by periodic monitoring of the concentration of glucose and glycosylated hemoglobin in the blood. The goal of treatment is to normalize these indicators. The concentration of glycosylated hemoglobin allows an assessment of glycemic control.
In the first weeks of treatment, careful monitoring of the patient’s condition is necessary due to the risk of hypoglycemia, especially with an increased risk of its development (patients who are not unwilling or unable to follow the doctor’s recommendations, most often elderly patients, with poor nutrition, irregular meals, with skipping meals, with a mismatch between exercise and carbohydrate intake, with changes in diet, with ethanol, especially in combination with skipping meals, with impaired renal function, with severe liver dysfunction, with some uncompensated endocrine system disorders (for example, some dysfunction of the thyroid gland and hormone deficiency in the anterior lobe of the pituitary gland or adrenal cortex; with the simultaneous use of certain other drugs that affect carbohydrate metabolism (see.section “Interaction with other medicinal products”).
In such cases, careful monitoring of blood glucose concentration is necessary.
The patient should inform the doctor about these risk factors and the symptoms of hypoglycemia, if any. If there are risk factors for hypoglycemia, it may be necessary to adjust the dose of this drug or of all therapy. This approach is used whenever a disease develops during therapy or a change in the patient’s lifestyle occurs.Symptoms of hypoglycemia, reflecting adrenergic antihypoglycemic regulation in response to developing hypoglycemia (see section “Side Effects”), may be less pronounced or absent altogether if hypoglycemia develops gradually, as well as in elderly patients, with autonomic neuropathy or with concurrent therapy beta-blockers: clonidine, guanethidine and other sympatholytics.
Almost always, hypoglycemia can be quickly relieved by immediate intake of carbohydrates (glucose or sugar, for example, a lump of sugar, fruit juice containing sugar, tea with sugar, etc.).etc.). For this purpose, the patient must carry at least at least 20 g of sugar with him. He may need the help of others to avoid complications. Sugar substitutes are ineffective.
From experience with other sulfonylureas, it is known that, despite the initial efficacy of the countermeasures taken, hypoglycemia can recur, so patients should remain under close supervision. The development of severe hypoglycemia requires immediate treatment and medical supervision, in some cases, inpatient treatment.
It is necessary to maintain target glycemia with the help of complex measures: adherence to diet and exercise, weight loss, and, if necessary, regular intake of hypoglycemic drugs. Patients should be educated about the importance of adhering to dietary guidelines and exercising regularly.
Clinical symptoms of inadequately regulated blood glucose include oliguria, thirst, incl. pathologically strong thirst, dry skin and others.If a patient is treated by a non-attending physician (for example, hospitalization, an accident, the need to visit a doctor on a day off, etc.), the patient must inform him about the diabetes mellitus and about the treatment being carried out.
In stressful situations (eg, trauma, surgery, infectious disease with fever) glycemic control may be impaired, and a temporary switch to insulin therapy may be required to provide adequate metabolic control.
Monitoring of renal function.
Metformin is excreted mainly by the kidneys. With impaired renal function, the risk of metformin accumulation and the development of lactic acidosis increases. When the concentration of creatinine in the blood serum exceeds the upper age limit of the norm, it is not recommended to take the drug Amaryl M. For elderly patients, careful titration of the metformin dose is necessary in order to select the minimum effective dose, since renal function decreases with age.Renal function in elderly patients should be monitored regularly, and, as a rule, the dose of metformin should not be increased to its maximum daily dose.
Concomitant use of other medicinal products may affect renal function or the elimination of metformin, or cause significant changes in hemodynamics.
X-ray studies with intravascular iodine-containing contrast agents [eg, intravenous urography, intravenous cholangiography, angiography, and computed tomography (CT) using a contrast agent]: contrasting intravenous iodine-containing contrast agents for X-ray studies can cause acute renal dysfunction; their use is associated with the development of lactic acidosis in patients taking metformin (see.section “Contraindications”). If such a study is planned, the drug Amaryl M must be canceled before the procedure and not resumed in the next 48 hours after the procedure. Treatment with Amaryl M can be resumed only after monitoring and obtaining normal renal function indicators.
Conditions in which hypoxia may develop
Collapse or shock of any origin, acute heart failure, acute myocardial infarction and other conditions characterized by hypoxemia and tissue hypoxia can also cause prerenal renal failure and increase the risk of lactic acidosis.If these conditions develop in patients taking this drug, the drug should be discontinued immediately.
For any planned surgical intervention, it is necessary to stop therapy with Amaryl M within 48 hours (except for small procedures that do not require restrictions in food and fluid intake), therapy cannot be resumed until oral food intake is restored and renal function is not recognized as normal.
Taking ethanol (preparations and drinks containing ethanol).
Ethanol enhances the effect of metformin on lactate metabolism. Patients should be warned against the use of drugs and drinks containing ethanol while taking the drug Amaryl M.
Since lactic acidosis has been associated with liver dysfunction in some cases, this drug should be avoided in patients with clinical or laboratory signs of liver damage.
Changes in the clinical state of a patient with previously controlled diabetes mellitus
A patient with diabetes mellitus, previously well controlled by metformin, is subject to immediate examination, especially in case of an indistinct and poorly recognized disease, to exclude ketoacidosis and lactic acidosis.The study should include: determination of the content of electrolytes and ketone bodies in the blood serum, determination of the concentration of glucose in the blood and, if necessary, the pH of the blood, the concentration in the blood of lactate, pyruvate and metformin. In the presence of any form of acidosis, you should immediately stop taking the drug Amaryl M and prescribe other drugs to maintain glycemic control.
Information for patients.
Patients should be informed about the possible risks and benefits of this drug, as well as about alternative treatments.The importance of adhering to dietary guidelines, performing regular exercise, regularly monitoring blood glucose, glycosylated hemoglobin, renal function and hematological parameters, as well as the risk of hypoglycemia, its symptoms and treatment, and conditions predisposing to its development.
Concentration of vitamin B12 in the blood.
A decrease in the concentration of vitamin B12 in the blood serum below normal in the absence of clinical manifestations was observed in about 7% of patients taking the drug Amaryl M, however, it is very rarely accompanied by anemia and with the withdrawal of this drug or with the introduction of vitamin B12 quickly was reversible.
Patients with insufficient intake or absorption of vitamin B12 are prone to a decrease in the concentration of vitamin B12. For such patients, it may be helpful to regularly, every 2-3 years, determine the concentration of vitamin B12 in the blood plasma.
Laboratory control of treatment safety.
Hematological parameters (hemoglobin or hematocrit, red blood cell count) and renal function parameters (serum creatinine concentration) should be periodically monitored at least once a year in patients with normal renal function, and at least 2-4 times a year in patients with serum creatinine concentration at the upper limit of normal and in elderly patients.
If necessary, the patient is shown appropriate examination and treatment of any obvious pathological changes.
Despite the fact that the development of megaloblastic anemia was rarely observed when taking metformin, if it is suspected, an examination should be carried out to exclude vitamin B12 deficiency.