Brand name: Amaryl
Drug class: Sulfonylureas
VA class: HS502
Molecular formula: C₂₄H₃₄N₄O₅S
CAS number: 93479-97-1

Medically reviewed by Drugs.com on Jun 11, 2024. Written by ASHP.

Introduction

Antidiabetic agent; sulfonylurea.

Uses for Glimepiride

Type 2 Diabetes Mellitus

Used alone or in combination with one or more other oral antidiabetic agents or insulin as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.

Used in fixed combination with pioglitazone in patients with type 2 diabetes mellitus who are already receiving a thiazolidinedione and a sulfonylurea separately or who do not achieve adequate glycemic control with thiazolidinedione or sulfonylurea monotherapy.

Current guidelines for the treatment of type 2 diabetes mellitus generally recommend metformin as first-line therapy in addition to lifestyle modifications in patients with recent-onset type 2 diabetes mellitus or mild hyperglycemia because of its well-established safety and efficacy (i.e., beneficial effects on glycosylated hemoglobin [hemoglobin A_1c; HbA_1c], weight, and cardiovascular mortality).

In patients with metformin contraindications or intolerance (e.g., risk of lactic acidosis, GI intolerance) or in selected other patients, some experts suggest that initial therapy with a drug from another class of antidiabetic agents (e.g., a glucagon-like peptide-1 [GLP-1] receptor agonist, sodium-glucose cotransporter 2 [SGLT2] inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, thiazolidinedione, basal insulin) may be acceptable based on patient factors.

May need to initiate therapy with 2 agents (e.g., metformin plus another drug) in patients with high initial HbA_1c (>7.5% or ≥1.5% above target). In such patients with metformin intolerance, some experts suggest initiation of therapy with 2 drugs from other antidiabetic drug classes with complementary mechanisms of action.

Consider early initiation of combination therapy for the treatment of type 2 diabetes mellitus to extend the time to treatment failure and more rapidly attain glycemic goals.

For patients with inadequate glycemic control on metformin monotherapy, consider patient comorbidities (e.g., atherosclerotic cardiovascular disease [ASCVD], established kidney disease, heart failure), hypoglycemia risk, impact on weight, cost, risk of adverse effects, and patient preferences when selecting additional antidiabetic agents for combination therapy.

Consider early introduction of insulin for severe hyperglycemia (e.g., blood glucose ≥300 mg/dL or HbA_1c >9–10%), especially if accompanied by catabolic manifestations (e.g., weight loss, hypertriglyceridemia, ketosis) or symptoms of hyperglycemia.

Glimepiride Dosage and Administration

General

• Adjust dosage according to tolerance and fasting glucose determinations. Monitor regularly (e.g., fasting blood or plasma glucose determinations) to determine therapeutic response and minimum effective dosage. Monitor HbA_1c every 3–6 months to determine the patient’s continued response to therapy.

• Use lowest effective dosage (either as monotherapy or in combination regimens) to reduce both fasting glucose concentrations and HbA_1c values to normal or near normal.

• If inadequate glycemic control and/or secondary failure occurs during monotherapy with glimepiride, may consider add-on therapy with metformin, insulin, or rosiglitazone. With concomitant glimepiride and metformin therapy, adjust dosage to the minimum effective level for each drug.

Oral Administration

Administer glimepiride alone or in fixed combination with pioglitazone once daily with the first main meal.

Dosage

Adults

Type 2 Diabetes Mellitus

Glimepiride Monotherapy

Oral

Initially, 1 or 2 mg of glimepiride once daily for previously untreated patients or patients transferred from other antidiabetic agents. In patients receiving 1 mg daily, increase dosage to 2 mg daily after 1–2 weeks if adequate glycemic control has not been achieved. Increase dosage in increments of no more than 2 mg daily at 1- to 2-week intervals up to a maximum of 8 mg once daily. Usual maintenance dosage is 1–4 mg once daily.

Maximum initial dosage should not exceed 2 mg once daily.

Glimepiride/Pioglitazone Fixed-combination Therapy

Oral

Select initial dosage based on patient’s current dosage of glimepiride (or another sulfonylurea agent) and/or pioglitazone.

Patients currently receiving glimepiride monotherapy: Usual initial dosage is 2 or 4 mg of glimepiride and 30 mg of pioglitazone once daily.

Patients transferring from monotherapy with other sulfonylureas: Initially, 2 mg of glimepiride and 30 mg of pioglitazone once daily. If patient is being transferred from a sulfonylurea with a long half-life (e.g., chlorpropamide [no longer commercially available in the US]), monitor closely for hypoglycemia during initial 1–2 weeks of the transition period.

Patients currently receiving pioglitazone monotherapy: Usual initial dosage is 2 mg of glimepiride and 30 mg of pioglitazone once daily.

Patients switching from concurrent therapy with separate glimepiride and pioglitazone preparations: Initiate fixed combination with 2 or 4 mg of glimepiride and 30 mg of pioglitazone once daily based on patient’s current dosage of glimepiride and pioglitazone. While switching therapy, carefully monitor patients whose hyperglycemia was not previously controlled with 15 mg of pioglitazone in combination with glimepiride.

Gradually titrate dosage as needed based on therapeutic response. Allow sufficient time (e.g., 8–12 weeks) to assess response. If additional glycemic control is needed, may increase dosage until maximum daily dosage of 8 mg of glimepiride and 45 mg of pioglitazone is reached.

Patients with type 2 diabetes mellitus and systolic dysfunction: Initiate glimepiride/pioglitazone fixed-combination at the lowest recommended dosage; use fixed-combination preparation only after patient has received pioglitazone 15 mg once daily as monotherapy and has safely tolerated dosage titration to 30 mg once daily. If subsequent dosage adjustment required, closely monitor for weight gain, edema, or other manifestations of CHF exacerbation.

Concomitant Glimepiride and Insulin Therapy

Oral

Initially, manufacturer recommends 8 mg of glimepiride once daily and a low insulin dosage in patients whose fasting plasma or serum glucose concentration exceeds 150 mg/dL despite appropriate oral antidiabetic monotherapy, diet, and exercise.

Adjust insulin dosage upward at approximately weekly intervals until adequate glycemic control is achieved. Periodic adjustments in insulin dosage may be necessary during continued combination therapy.

Switching Therapy from Other Sulfonylurea Agents

Oral

Initially, 1–2 mg of glimepiride once daily. May discontinue other sulfonylurea agents immediately. When switching therapy from chlorpropamide (a sulfonylurea with a long elimination half-life; no longer commercially available in the US), monitor closely for hypoglycemia during the initial 1–2 weeks of the transition period.

The initial dosage of glimepiride during the switch from other therapy should not exceed 2 mg daily.

Prescribing Limits

Adults

Type 2 Diabetes Mellitus

Oral

Glimepiride monotherapy: Maximum 8 mg daily.

Fixed combination with pioglitazone: Maximum 8 mg of glimepiride and 45 mg of pioglitazone daily.

Special Populations

Hepatic Impairment

Glimepiride monotherapy: Initially, 1 mg once daily. Conservative initial and maintenance dosages recommended.

Renal Impairment

Glimepiride monotherapy: Initially, 1 mg once daily. Titrate dosage upward based on fasting glucose concentrations. Dosages >1 mg daily may not be required if Cl_cr <22 mL/minute.

Geriatric Patients

Geriatric individuals may be particularly sensitive to the hypoglycemic effects of glimepiride.

Glimepiride monotherapy: Initially, 1 mg once daily. Titrate dosage upward with care. Conservative initial and maintenance dosages recommended.

Debilitated or Malnourished Patients

These individuals may be particularly sensitive to the hypoglycemic effects of glimepiride.

Glimepiride monotherapy: Initially, 1 mg once daily. Conservative initial and maintenance dosages recommended.

Cautions for Glimepiride

Contraindications

• Known hypersensitivity to glimepiride or any ingredient in formulation.

• Diabetic ketoacidosis, with or without coma.

Warnings/Precautions

Warnings

Cardiovascular Effects

Increased cardiovascular mortality reported with certain other antidiabetic agents (i.e., tolbutamide, phenformin). However, the American Diabetes Association (ADA) considers the benefits of intensive glycemic control with insulin or sulfonylureas to outweigh the risks overall.

General Precautions

Hypoglycemia

Possible severe hypoglycemia, especially in geriatric, debilitated, or malnourished patients and those with adrenal, pituitary, hepatic, or renal insufficiency. Increased risk of hypoglycemia with strenuous exercise, alcohol ingestion, insufficient caloric intake, or use in combination with other oral antidiabetic agents (e.g., rosiglitazone, metformin).

Hypoglycemia may be difficult to recognize in geriatric patients and in those receiving β-adrenergic blocking agents.

Appropriate patient selection and careful dosing are important to avoid glimepiride-induced hypoglycemia.

Loss of Glycemic Control

Possible loss of glycemic control during periods of stress (e.g., fever, trauma, infection, surgery); administration of insulin may be required.

Efficacy of therapy may decrease over time (secondary failure). Addition of metformin or insulin to therapy may be required. (See Diabetes Mellitus under Uses.)

Use of Fixed Combinations

When used in fixed combination with pioglitazone or other drugs, consider the cautions, precautions, and contraindications associated with pioglitazone or other concomitant agent(s).

Specific Populations

Pregnancy

Category C.

Many experts recommend use of insulin during pregnancy to maintain optimum control of blood glucose concentrations.

Lactation

Distributed into milk in rats; other sulfonylureas distributed into human milk. Use not recommended. If oral antidiabetic therapy discontinued and diet alone is inadequate for optimal glycemic control, consider institution of insulin.

Pediatric Use

Glimepiride: Safety and efficacy not established in children <16 years of age.

Fixed combination with pioglitazone: Safety and efficacy not established in pediatric patients.

ADA states that use of oral antidiabetic agents may be considered in children with type 2 diabetes mellitus because of the greater compliance and convenience and lack of evidence demonstrating better efficacy of insulin for type 2 diabetes mellitus.

Geriatric Use

No substantial differences in safety, efficacy, or pharmacokinetics relative to younger adults, but increased sensitivity cannot be ruled out.

Possible increased risk of adverse effects due to age-related decreases in renal function. Renal function monitoring recommended, and care should be taken in dosage selection. (See Geriatric Patients under Dosage and Administration.)

Increased risk of hypoglycemia; may be difficult to recognize in geriatric patients.

Hepatic Impairment

Increased risk of hypoglycemia; conservative dosing recommended. (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Decreased clearance.

Increased risk of hypoglycemia; conservative dosing recommended. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Dizziness, asthenia, headache, nausea.

Drug Interactions

Metabolized by CYP2C9.

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors and inducers of CYP2C9; possible alteration in metabolism of glimepiride.

Protein-bound Drugs

Potential pharmacokinetic interaction (increased hypoglycemic effect). (See Specific Drugs under Interactions.)

Close observation recommended when initiating or discontinuing concomitant therapy with a highly protein-bound drug.

Drugs with Hyperglycemic Effects

Potential pharmacologic interaction (loss of glycemic control).

Close observation recommended when initiating or discontinuing concomitant therapy.

Specific Drugs

Glimepiride Pharmacokinetics

Absorption

Bioavailability

Completely absorbed; oral bioavailability of 100%. Peak blood concentrations attained within 2–3 hours.

Onset

Time to maximum effect about 2–3 hours.

Duration

Glucose-lowering effect persists for 24 hours.

Food

Food increases the time to peak blood concentrations by about 12%. The mean peak blood concentration and AUC are decreased by 8 and 9%, respectively.

Distribution

Extent

Volume of distribution: 8.8 L (113 mL/kg).

Not known if glimepiride is distributed into human milk.

Plasma Protein Binding

>99.5%.

Elimination

Metabolism

Metabolized by CYP2C9 and by cytosolic enzymes to active and inactive metabolites.

Elimination Route

Excreted in urine (60%) and feces (40%) predominantly as metabolites.

Half-life

Averages 5.3 hours after a single dose in healthy individuals. Averages 9.2 hours in patients with type 2 diabetes mellitus at steady state.

Special Populations

Renal impairment: Decreased serum drug concentrations and increased concentrations and half-lives of the metabolites.

Geriatric patients: At steady state, lower mean AUC (13%) and increased clearance (11%) compared with younger patients.

Stability

Storage

Oral

Tablets

Glimepiride: Well-closed containers at 15–30°C.

Actions

• Reduces both fasting and postprandial blood glucose concentrations and HbA_1c in a dose-dependent manner.

• Lowers blood glucose concentration principally by stimulating postprandial secretion of endogenous insulin from the beta cells of the pancreas. Also enhances peripheral sensitivity to insulin.

• Provides overall glycemic control without appreciably increasing fasting insulin secretion.

• Ineffective in the absence of functioning beta cells.

Advice to Patients

• Inform patients of the potential risks and advantages of glimepiride therapy and of alternative forms of treatment.

• Importance of taking the medication each morning with breakfast or with the first main meal.

• Importance of adhering to diet and exercise regimen.

• Importance of hygiene and avoidance of infection.

• Advise patients about the nature of diabetes mellitus, prevention and detection of complications, and importance of glycemic control.

• Importance of appropriate management of hypoglycemia and hyperglycemia. Risks of hypoglycemia. Importance of patients and responsible family members understanding symptoms and treatment of hypoglycemic reactions and identifying conditions that predispose to the development of such reactions.

• Importance of regular monitoring of blood glucose (preferably self-monitoring) and of HbA_1c.

• Discuss potential for alterations in dosage requirements in special situations (e.g., illness, fever, trauma, infection, surgery); importance of informing clinician promptly if such situations occur.

• Importance of understanding primary and secondary failure to therapy.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., type 1 diabetes mellitus, kidney or liver disease).

• Advise patients receiving β-adrenergic blocking agents about potential risk for hypoglycemia.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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