Glimepirida

Glimepirida Uses, Dosage, Side Effects, Food Interaction and all others data.

Glimepirida stimulates the insulin release from pancreatic β-cells and reduces glucose output from the liver. It also increases insulin sensitivity at peripheral target sites.

Glimepirida stimulates the secretion of insulin granules from the pancreatic beta cells and improves the sensitivity of peripheral tissues to insulin to increase peripheral glucose uptake, thus reducing plasma blood glucose levels and glycated hemoglobin (HbA1C) levels. A multi-center, randomized, placebo-controlled clinical trial evaluated the efficacy of glimepiride (1–8 mg) as monotherapy titrated over 10 weeks compared with placebo in T2DM subjects who were not controlled by diet alone. In this study, there was a reduction in fasting plasma glucose (FPG) by 46 mg/dL, post-prandial glucose (PPG) by 72 mg/dL, and HbA1c by 1.4% more than the placebo. In another randomized study comprising of patients with T2DM receiving either placebo or one of the three doses (1, 4, or 8 mg) of glimepiride during a 14-week study period, all glimepiride regimens significantly reduced FPG, PPG, and HbA1c values (P < 0.001) compared to placebo by the end of the study period. The 4- and 8-mg doses of glimepiride were more effective than the 1-mg dose; however, the 4-mg dose provided a nearly maximal antihyperglycemic effect.

Trade Name Glimepirida
Availability Prescription only
Generic Glimepiride
Glimepiride Other Names Glimepirida, Glimépiride, Glimepiride, Glimepiridum
Related Drugs Farxiga, metformin, Trulicity, Lantus, Victoza, Tresiba, Levemir
Type
Formula C24H34N4O5S
Weight Average: 490.62
Monoisotopic: 490.224991385
Protein binding

Plasma protein binding of glimepiride is greater than 99.5%.

Groups Approved
Therapeutic Class Sulfonylureas
Manufacturer
Available Country Portugal
Last Updated: September 19, 2023 at 7:00 am
Glimepirida
Glimepirida

Uses

Glimepirida is used for an adjunct to diet to lower the blood glucose in patients with non-insulin-dependent diabetes mellitus (type 2 diabetes) whose hyperglycemia cannot be controlled by diet, physical exercise and weight reduction.

Glimepirida is also used for use in combination with Insulin to lower blood glucose in patients whose hyperglycaemia can not be controlled by diet and exercise or in conjunction with an oral hypoglycaemic agent.

Glimepirida is also used to associated treatment for these conditions: Type 2 Diabetes Mellitus

How Glimepirida works

ATP-sensitive potassium channels on pancreatic beta cells that are gated by intracellular ATP and ADP. The hetero-octomeric complex of the channel is composed of four pore-forming Kir6.2 subunits and four regulatory sulfonylurea receptor (SUR) subunits. Alternative splicing allows the formation of channels composed of varying subunit isoforms expressed at different concentrations in different tissues. In pancreatic beta cells, ATP-sensitive potassium channels play a role as essential metabolic sensors and regulators that couple membrane excitability with glucose-stimulated insulin secretion (GSIS). When there is a decrease in the ATP:ADP ratio, the channels are activated and open, leading to K+ efflux from the cell, membrane hyperpolarization, and suppression of insulin secretion. In contrast, increased uptake of glucose into the cell leads to elevated intracellular ATP:ADP ratio, leading to the closure of channels and membrane depolarization. Depolarization leads to activation and opening of the voltage-dependent Ca2+ channels and consequently an influx of calcium ions into the cell. Elevated intracellular calcium levels causes the contraction of the filaments of actomyosin responsible for the exocytosis of insulin granules stored in vesicles. Glimepirida blocks the ATP-sensitive potassium channel by binding non-specifically to the B sites of both sulfonylurea receptor-1 (SUR1) and sulfonylurea receptor-2A (SUR2A) subunits as well as the A site of SUR1 subunit of the channel to promote insulin secretion from the beta cell.

Dosage

Glimepirida dosage

In principle, the dosage of Glimepirida is governed by the desired blood sugar level. The dosage of Glimepirida must be the lowest which is sufficient to achieve the desired metabolic control.

The initial and the maintenance doses are set based on the results of regular checking of glucose in blood and urine. Monitoring of glucose levels in blood and urine also serves to detect either primary or secondary failure of therapy.

Initial dose and dose titration: Usual initial dose is 1 mg once daily. If necessary, the daily dose can be increased. Any increase can be based on regular blood sugar monitoring, and should be gradual, i.e., at intervals of one to two weeks and carried out step wise at follows: 1 mg-2 mg-3 mg-4 mg-6 mg.

Dose range in patients with well controlled diabetes: Usual dose range in patients with well controlled diabetes is 1 to 4 mg daily.

Distribution of doses: Timing and distribution of doses are decided by the physician, in consideration of the patient's current life style. Normally, a single daily dose is sufficient. This should be taken immediately before a substantial breakfast or - if none is taken - immediately before the first main meals. It is very important not to skip meals after taking the drug.

Secondary dosage adjustment: As the control of diabetes improves, sensitivity to insulin increases; therefore, Glimepirida requirement may fall as treatment proceeds. To avoid hypoglycaemia, timely dose reduction or cessation of Glimepirida therapy must be considered.A dose adjustment must also be considered whenever the patient's weight or life style changes, or other factors arise which cause an increased susceptibility to hypo- or hyperglycaemia.

Changeover from other oral antidiabetics to Glimepirida: There is no exact dosage relationship between Glimepirida and other oral blood sugar lowering agents. When substituting Glimepride for other such agents, the initial daily dose is 1 mg; this applies even in changeover from the maximum dose of other oral blood sugar lowering agents. Any dose increase should be in accordance with guideline given above in initial dose and dose titration.

Consideration must be given to the potency and duration of action of the previous blood sugar lowering agent. It may be necessary to interrupt treatment to avoid additive effects which would increase the risk of hypoglycaemia.

Diaryl tablet must be swallowed without chewing and with sufficient amount of liquid (approximately ½ glass).

Side Effects

Hypoglycaemia, temporary visual impairment, nausea, vomiting, diarrhoea, abdominal pain, urticaria & fall in blood pressure.

Toxicity

The oral LD50 value in rats is > 10000 mg/kg. The intraperitoneal LD50 value in rats is reported to be 3950 mg/kg . Although glimepiride is reported to have fewer risks of hypoglycemia compared to other sulfonylureas such as glyburide, overdosage of glimepiride may result in severe hypoglycemia with coma, seizure, or other neurological impairment may occur. This can be treated with glucagon or intravenous glucose. Continued observation and additional carbohydrate intake may be necessary since hypoglycemia may recur after apparent clinical recovery.

In a study of rats given doses of up to 5000 parts per million (ppm) in complete feed for 30 months, there were no signs of carcinogenesis. Meanwhile, the administration of glimepiride at a dose much higher than the maximum human recommended dose for 24 months in mice resulted in an increase in benign pancreatic adenoma formation in a dose-related manner, which was thought to be the result of chronic pancreatic stimulation. Glimepirida was non-mutagenic in in vitro and in vivo mutagenicity studies. In male and female rat studies, glimepiride was shown to have no effects on fertility.

Precaution

In the initial weeks of treatment, the risk of hypoglycaemia may be increased and necessitates careful monitoring. If such risk is present it may be necessary to adjust the dosage of Glimepirida. Hypoglycaemia can almost always be promptly controlled by immediate intake of carbohydrates (glucose or sugar, e.g., sugar sweetened fruit juice or sugar sweetened tea)

Interaction

Potentiation of the blood-sugar-lowering effect may occur with Insulin and other oral anti-diabetics, ACE inhibitors, Allopurinol, anabolic steroids and male sex hormones, Chloramphenicol, coumarin derivatives, Fluoxetine, MAO inhibitors, Miconazole, Para-aminosalicyclic acid, Pentoxifylline (high dose parenteral), Phenylbutazone, Oxyphenbutazone, quinolones, salicylates, sulphonamides, tetracyclines, β blockers.

Weakening of the blood-sugar-lowering effect may occur with Acetazolamide, barbiturates, corticosteroids, Diazoxide, diuretics, Epinephrine and other sympathomimetic agents, laxative, oestrogens and progestogens, phenothiazines, Phenytoin, Rifampicin, and thyroid hormones.

H2 -receptor antagonists, Clonidine and Reserpine may lead to either potentiation or weakening of the blood-sugar-lowering effect.

Both acute and chronic alcohol intake may potentiate or weaken the blood-sugar-lowering action of Glimepirida unpredictably.

Food Interaction

  • Avoid alcohol. Acute and chronic alcohol intake may unpredictably affect the glucose-lowering action of glimepiride.
  • Take with food. The manufacturer recommends administration with the first meal of the day.

[Moderate] GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes.

Hypoglycemia most frequently occurs during acute consumption of alcohol.

Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise.

The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia.

Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion.

By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia.

Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes.

A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis.

Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan.

Alcohol should not be consumed on an empty stomach or following exercise.

Volume of Distribution

Following intravenous dosing in healthy subjects, the volume of distribution was 8.8 L (113 mL/kg).

Elimination Route

Glimepirida is completely absorbed after oral administration within 1 hour of administration with a linear pharmacokinetics profile. Following administration of a single oral dose of glimepiride in healthy subjects and with multiple oral doses with type 2 diabetes, the peak plasma concentrations (Cmax) were reached after 2 to 3 hours post-dose. Accumulation does not occur after multiple doses. When glimepiride was given with meals, the time to reach Cmax was increased by 12% while the mean and AUC (area under the curve) were decreased by 8 to 9%, respectively. In a pharmacokinetic study of Japanese patients with T2DM, Cmax value in once-daily dose was higher than those in twice-daily doses. The absolute bioavailability of glimepiride is reported to be complete following oral administration.

Half Life

The elimination half-life of glimepiride is approximately 5 to 8 hours, which can increase up to 9 hours following multiple doses.

Clearance

A single-dose, crossover, dose-proportionality (1, 2, 4, and 8 mg) study in normal subjects and from a single- and multiple-dose, parallel, dose proportionality (4 and 8 mg) study in patients with type 2 diabetes (T2D) were performed. In these studies, the total body clearance was 52.1 +/- 16.0 mL/min, 48.5 +/- 29.3 mL/min in patients with T2D given a single oral dose, and 52.7 +/- 40.3 mL/min in patients with T2D given multiple oral doses. Following intravenous dosing in healthy subjects, the total body clearance was 47.8 mL/min.

Elimination Route

Following oral administration of glimepiride in healthy male subjects, approximately 60% of the total radioactivity was recovered in the urine in 7 days, with M1 and M2 accounting for 80-90% of the total radioactivity recovered in the urine. The ratio of M1 to M2 was approximately 3:2 in two subjects and 4:1 in one subject. Approximately 40% of the total radioactivity was recovered in feces where M1 and M2 accounted for about 70% of the radioactivity and a ratio of M1 to M2 being 1:3. No parent drug was recovered from urine or feces.

Pregnancy & Breastfeeding use

Pregnancy: Glimepirida must not be taken during pregnancy; a changeover to Insulin is necessary. Patients planning a pregnancy must inform their physician, and should be shifted to Insulin.

Lactation: Ingestion of Glimepirida with breast milk may harm the child. Therefore, Glimepirida must not be taken by lactating women. Either a changeover or a complete discontinuation of breast-feeding is necessary.

Contraindication

Glimepirida is not suitable for the treatment of insulin dependent (type-I) diabetes mellitus, or of diabetic pre-coma or coma. Glimepirida must not be used in patients hypersensitive to Glimepirida or other sulphonylureas.

Special Warning

Pediatric use: Safety and effectiveness in pediatric patients have not been established.

Geriatric use: No overall differences in safety or effectiveness were observed between elderly and adult subjects, but greater sensitivity of some older individuals cannot be ruled out. The drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Use in renal insufficiency: A starting dose of 1 mg glimepiride may be given to NIDDM patients with kidney disease, and the dose may be titrated based on fasting blood glucose levels. 

Use in hepatic insufficiency: No studies were performed in patients with hepatic insufficiency. Adverse reactions: Hypoglycemia. Adverse events, other than hypoglycemia, are dizzines, asthenia, headache, and nausea.

Acute Overdose

Accidental or intentional overdose may cause severe and prolonged hypoglycemia which may be life-threatening. In case of overdosage with Glimepirida, a doctor must be notified immediately. At the first signs of hypoglycemia, the patient must immediately take sugar, preferably glucose, unless a doctor has already started care.

Storage Condition

Store at 25° C.

Innovators Monograph

You find simplified version here Glimepirida

Glimepirida contains Glimepiride see full prescribing information from innovator Glimepirida Monograph, Glimepirida MSDS, Glimepirida FDA label

FAQ

What is Glimepirida used for?

Glimepirida is used to treat high blood sugar levels caused by type 2 diabetes. It is an anti-diabetic medication used to treat type 2 diabetes. Glimepirida is less preferred than metformin. Use is recommended together with diet and exercise. It may be used alone, or in combination with insulin or another oral medicine such as metformin.

How safe is Glimepirida?

Glimepirida is safe to take for a long time. There's no evidence that it harms your general health or your pancreas.

How does Glimepirida work?

Glimepirida lowers blood sugar by causing the pancreas to produce insulin and helping the body use insulin efficiently. Glimepirida will only help lower blood sugar in people whose bodies produce insulin naturally.

What are the common side effects of Glimepirida?

The most common side effects are feeling sick, indigestion and diarrhoea. Glimepirida can sometimes give you low blood sugar. Carry some sweets or fruit juice with you to help when this happens. Some people find they put on weight with Glimepirida.

Is Glimepirida safe during pregnancy?

Glimepirida should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

Is Glimepirida safe during breastfeeding?

Breastfeeding is not recommended during use of Glimepirida.

Can I drink alcohol with Glimepirida?

Avoid drinking alcohol. It lowers blood sugar and may interfere with your diabetes treatment.

Can I drive after taking Glimepirida?

If your blood sugar levels are stable, your ability to drive, cycle or use machines or tools shouldn't be affected by Glimepirida. However, if your blood sugar levels become too low, this can reduce your concentration. If this happens to you, do not drive, cycle, or use machines or tools until you feel better.

When should be taken of Glimepirida?

You'll usually take Glimepirida once a day. Most people take it in the morning with their breakfast. If you don't eat breakfast, make sure you take it with your first meal of the day.

Can I take Glimepirida on an empty stomach?

Take Glimepirida with food.Having an empty stomach and taking Glimepirida can cause your blood sugar to become too low.

How long does Glimepirida take to work?

Glimepirida reduces blood sugar levels in 2 to 3 hours.

How long does Glimepirida stay in my system?

Glimepirida tablets begin to lower your blood sugar 30 minutes after you take a dose. Glimepirida reaches its full effects 1 to 3 hours after each dose. Glimepirida tablets begin to lower your blood sugar 2 to 3 hours after you take a dose.

Can I take Glimepirida long term?

Glimepirida is used for long term treatment. It comes with serious risks if you don't take it as prescribed. If you don't taken Glimepirida  at all, you may still have high blood sugar levels.

Is Glimepirida hard on the kidneys?

Glimepirida is safe, effective and has clearly-definable pharmacokinetics in diabetic patients with renal impairment. The increased plasma elimination of Glimepirida with decreasing kidney function is explainable on the basis of altered protein binding with an increase in unbound drug.

Is Glimepirida bad for my heart?

You should not use this Glimepirida if you have severe or uncontrolled heart failure, active bladder cancer, or diabetic ketoacidosis. Glimepirida can cause or worsen congestive heart failure.

When can I stop taking Glimepirida?

Do not stop taking Glimepirida without talking with your doctor first, even if you feel better. This type 2 diabetes drug affects blood sugar, so any changes in your dose will affect your blood sugar.

What happens if I stop taking Glimepirida?

Do not stop taking Glimepirida without talking to your doctor. If you stop taking Glimepirida suddenly your diabetes may get worse. If you want to stop taking your medicine, speak to your doctor. They may be able to suggest an alternative treatment for your diabetes.

How many hours does Glimepirida last?

Glimepirida takes up to three hours for maximum effect and lasts for about a day.

Can I just stop taking Glimepirida?

Do not stop taking Glimepirida without talking to your doctor.

Does Glimepirida affect blood pressure?

Glimepirida associated to a significant improvement in the long-term blood pressure control.

Who should not take Glimepirida?

You should not use Glimepirida if you have diabetic ketoacidosis, or if you are allergic to Glimepirida.

What happens if I miss a dose of Glimepirida?

Take Glimepirida as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention. A Glimepirida overdose can cause life-threatening hypoglycemia.
Symptoms of severe hypoglycemia include extreme weakness, confusion, tremors, sweating, fast heart rate, trouble speaking, nausea, vomiting, rapid breathing, fainting, and seizure.

*** Taking medicines without doctor's advice can cause long-term problems.
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