Glimepiride

Generic Name

Glimepiride

Brand Names

Amaryl

Glimy

Glimin

Solosa

Glimide

Glimestar

Available in oral tablet form in strengths of 1 mg, 2 mg, 3 mg, and 4 mg

Drug Class

Second-generation sulfonylurea

Oral hypoglycemic agent

ATP-sensitive potassium channel blocker

Mechanism of Action

Glimepiride lowers blood glucose by stimulating the release of insulin from pancreatic beta-cells

It binds to the sulfonylurea receptor (SUR1) component of the ATP-sensitive potassium (K⁺ATP) channels on beta-cell membranes

This binding causes potassium channel closure, leading to cell membrane depolarization and opening of voltage-dependent calcium channels

Calcium influx stimulates the exocytosis of insulin granules

Glimepiride may also increase peripheral insulin sensitivity and hepatic glucose utilization, but its primary action is insulin secretion

Indications

Type 2 diabetes mellitus as an adjunct to diet and exercise

Monotherapy or combination therapy with other antidiabetic agents including metformin, pioglitazone, DPP-4 inhibitors, or insulin

Off-label uses

Not recommended for type 1 diabetes or diabetic ketoacidosis

Not indicated for gestational diabetes, although sometimes used under strict supervision

Dosage and Administration

Adults

Initial dose: 1 mg orally once daily with breakfast or first main meal

Titration: Increase by 1–2 mg every 1–2 weeks based on blood glucose response

Usual maintenance dose: 1–4 mg/day

Maximum dose: 8 mg/day

Dose adjustments required in renal or hepatic impairment

Geriatric Patients

Start at 1 mg/day due to increased risk of hypoglycemia

Careful titration recommended

Pediatric Use

Not approved for use in children under 18 years due to limited data

Pharmacokinetics

Rapidly and completely absorbed after oral administration

Peak plasma concentration reached in 2–3 hours

Half-life: 5–9 hours

Metabolized primarily in the liver by CYP2C9 into M1 (active) and M2 (inactive) metabolites

Excreted via urine (60%) and feces (40%)

Food slightly delays absorption but does not significantly affect efficacy

Contraindications

Known hypersensitivity to glimepiride or other sulfonylureas/sulfonamides

Type 1 diabetes mellitus

Diabetic ketoacidosis, with or without coma

Severe hepatic or renal impairment

Pregnancy and breastfeeding unless no alternatives exist

Warnings and Precautions

Hypoglycemia risk increased in elderly, malnourished, or those with renal/hepatic dysfunction

Alcohol use can potentiate hypoglycemia

May mask adrenergic symptoms of hypoglycemia (e.g., tremor, palpitations)

Caution in patients with G6PD deficiency due to risk of hemolytic anemia

Photosensitivity has been reported

Not a substitute for insulin in type 1 diabetes or DKA

Loss of glycemic control may occur over time; therapy reassessment may be needed

Hypoglycemia may be severe and prolonged

Adverse Effects

Very Common to Common

Hypoglycemia (especially with fasting, excessive dose, or alcohol)

Weight gain

Nausea

Dizziness

Headache

Asthenia

Uncommon

Gastrointestinal upset (vomiting, diarrhea)

Hematologic changes: leukopenia, thrombocytopenia, hemolytic anemia

Allergic skin reactions: rash, urticaria, pruritus

Rare

Severe hypoglycemia with CNS depression

Cholestatic jaundice or hepatitis

Visual disturbances at treatment initiation (due to rapid glucose changes)

Hyponatremia due to SIADH

Photosensitivity reactions

Pancreatitis

Elevated liver enzymes

Pregnancy and Lactation

Pregnancy

Category C

Animal studies showed potential teratogenic effects

Not recommended during pregnancy

Insulin is preferred for blood glucose control during pregnancy

Lactation

Excreted in breast milk

Use not recommended during breastfeeding due to potential risk of hypoglycemia in the infant

Drug Interactions

Potentiation of Hypoglycemic Effect

Other antidiabetic agents (metformin, insulin, DPP-4 inhibitors)

NSAIDs (e.g., aspirin)

MAO inhibitors

Beta-blockers (may also mask hypoglycemia symptoms)

Fluoroquinolones

Sulfonamides

Warfarin

Alcohol

Gemfibrozil

Miconazole

Azole antifungals

Reduction of Hypoglycemic Effect

Thiazide diuretics

Corticosteroids

Phenytoin

Nicotinic acid

Sympathomimetics (e.g., epinephrine, salbutamol)

Rifampicin

Oral contraceptives

Enzyme Modulators

CYP2C9 inhibitors (e.g., fluconazole) increase glimepiride levels

CYP2C9 inducers (e.g., rifampicin) may reduce efficacy

Monitoring Parameters

Fasting and postprandial blood glucose levels

HbA1c every 3 months

Signs of hypoglycemia (sweating, shakiness, confusion)

Renal and hepatic function tests periodically

Weight changes

Complete blood count (periodically, especially in long-term therapy)

Counseling Points

Take with breakfast or first main meal to reduce hypoglycemia risk

Do not skip meals while taking glimepiride

Be aware of hypoglycemia symptoms and keep a source of glucose on hand

Avoid alcohol due to enhanced risk of hypoglycemia

Inform healthcare providers of sulfonylurea use before surgeries

Do not drive or operate machinery if feeling drowsy or lightheaded

Wear medical identification indicating diabetes and glimepiride use

Comparative Notes

Glimepiride vs Glibenclamide (Glyburide)

Glimepiride has a lower risk of hypoglycemia and less pronounced weight gain

Preferred in elderly due to better safety profile

Glimepiride vs Gliclazide

Both are second-generation sulfonylureas

Gliclazide may have a more favorable cardiovascular profile

Glimepiride has longer action and stronger insulinotropic effect

Glimepiride vs Metformin

Metformin is first-line agent in type 2 diabetes

Glimepiride is added when metformin monotherapy is insufficient

Metformin does not cause hypoglycemia and promotes weight neutrality or loss

Glimepiride more likely to cause hypoglycemia and weight gain

Glimepiride vs DPP-4 Inhibitors (e.g., Sitagliptin)

DPP-4 inhibitors have lower hypoglycemia risk and are weight-neutral

Glimepiride is more potent in insulin stimulation

Used when cost is a concern or when DPP-4 inhibitors are contraindicated

Legal and Regulatory Status

Prescription-only medicine in most countries

Included in WHO Model List of Essential Medicines

Widely available and cost-effective