Schedule H

Oral

• Tablets: 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg

• Fixed-dose combinations (FDCs): Glimepiride + Metformin (1/500 mg, 1/1000 mg, 2/500 mg, 2/1000 mg); Glimepiride + Metformin + Pioglitazone; Glimepiride + Metformin + Voglibose

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Type 2 Diabetes Mellitus (T2DM) — Monotherapy or Combination Therapy

Parameter Recommendation

Starting dose 1 mg once daily with breakfast (0.5 mg in elderly/frail)

Titration Increase by 1 mg every 1–2 weeks based on fasting plasma glucose response

Usual maintenance dose 1–4 mg once daily

Maximum dose 6 mg once daily (8 mg rarely used in Indian practice)

Key Clinical Notes:

Administer with first main meal of the day (preferably breakfast)

• Best suited for lean, insulinopenic T2DM patients with preserved beta-cell function

• When combining with insulin: reduce insulin dose by 30–50% at initiation to prevent hypoglycaemia

• ICMR 2022 recommends SGLT2 inhibitors or DPP-4 inhibitors over sulfonylureas in patients with obesity, cardiovascular disease, or CKD

Use in Combination with Metformin

Parameter Recommendation

Starting dose 1 mg once daily (add to existing metformin)

Titration Increase by 1 mg every 2 weeks based on FPG/HbA1c

Usual maintenance dose 1–2 mg once daily

Maximum dose 4 mg once daily in combination

Key Clinical Notes:

• Higher hypoglycaemia risk than metformin monotherapy; counsel patient on recognition and management

• FDC tablets improve adherence but reduce dose flexibility

Use in Combination with Insulin

Parameter Recommendation

Starting dose 1 mg once daily

Titration Increase cautiously every 2–4 weeks

Usual maintenance dose 1–2 mg once daily

Maximum dose 4 mg once daily

Key Clinical Notes:

• Reduce basal insulin dose by 30–50% when adding glimepiride

• Significant hypoglycaemia risk; ensure strict glucose monitoring

• Consider this combination only when other oral agents insufficient

Secondary Indications — Adults (Off-label, if any)

Not applicable.

No validated off-label adult indications exist for glimepiride in Indian clinical practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Type 2 Diabetes Mellitus in Paediatric Population:

Parameter Recommendation

Approval status NOT APPROVED in India for patients <18 years

Minimum age for off-label use ≥12 years (under specialist supervision only)

Starting dose 0.5 mg once daily with breakfast

Titration Increase by 0.5–1 mg every 2–4 weeks

Maximum dose 2 mg once daily

Safety Monitoring Requirements:

• Frequent capillary blood glucose monitoring (minimum twice daily initially)

• HbA1c every 3 months

• Weight monitoring (sulfonylureas promote weight gain)

• Educate caregivers on hypoglycaemia recognition and management

• Keep glucose tablets/juice accessible at all times

Key Clinical Notes:

• Use only under paediatric endocrinologist supervision

• Metformin remains first-line in paediatric T2DM as per IAP guidelines

• Consider only when metformin alone inadequate or contraindicated

• NOT recommended in children <12 years or in Type 1 Diabetes

Secondary Indications — Paediatrics (Off-label, if any)

Indication Dose Duration Notes

MODY (Maturity-Onset Diabetes of the Young) — HNF1A/HNF4A subtypes 0.5–1 mg once daily Long-term OFF-LABEL; Specialist only. Evidence: Case series; genetic confirmation required before use. Very sensitive to sulfonylureas — start very low.

Key Clinical Notes:

• Active metabolites (M1, M2) renally excreted; accumulate in renal impairment

• DPP-4 inhibitors (linagliptin) or short-acting insulin preferred in advanced CKD

• Type 1 diabetes mellitus

• Diabetic ketoacidosis (with or without coma)

• Hyperosmolar hyperglycaemic state

• Severe renal impairment (eGFR <30 ml/min/1.73m²)

• Severe hepatic impairment (Child-Pugh C)

• Hypersensitivity to glimepiride, other sulfonylureas, or sulfonamide derivatives

• Pregnancy

• Lactation

• Elderly patients — increased hypoglycaemia risk and delayed recognition

• G6PD deficiency — haemolytic anaemia reported with sulfonylureas (rare)

• Adrenal or pituitary insufficiency — impaired counter-regulatory response

• Malnutrition, irregular meal patterns, or alcohol intake

• Patients fasting for religious or medical reasons

• Acute illness, trauma, or perioperative period (consider temporary insulin switch)

• Concurrent use of other hypoglycaemic agents

• Shift workers with inconsistent meal timings

• History of sulfonamide allergy — cross-reactivity possible (use with caution)

Parameter Recommendation

Risk category Not recommended; crosses placenta

Fetal risks Neonatal hypoglycaemia, macrosomia

Preferred alternative Insulin (all trimesters) as per ICMR and FOGSI guidelines

Preconception Discontinue at least 1 month prior to planned conception and switch to insulin

If inadvertent exposure Monitor fetal growth (ultrasound); prepare for neonatal glucose monitoring post-delivery

Monitoring Fetal growth, amniotic fluid; neonatal blood glucose in first 24–48 hours

Parameter Recommendation

Compatibility Not compatible with breastfeeding

Milk excretion Excreted in breast milk (animal data); potential risk to infant

Preferred alternatives Insulin (safe); Metformin (acceptable if breastfeeding-compatible needed)

If inadvertent exposure Monitor infant for hypoglycaemia (poor feeding, lethargy, jitteriness, seizures), weight gain

Parameter Recommendation

Starting dose 0.5 mg once daily with breakfast

Titration Slow; increase by 0.5 mg every 2–4 weeks

Maximum dose 2 mg once daily in frail elderly

Special risks Prolonged hypoglycaemia (may persist >24 hours), atypical hypoglycaemia presentation (confusion, falls, focal neurological deficits), reduced renal reserve, cognitive impairment masking symptoms

Monitoring Regular capillary glucose; assess renal function every 6 months; fall risk assessment

Interacting Drug Effect Mechanism Management

Fluconazole / Miconazole Severe hypoglycaemia CYP2C9 inhibition → increased glimepiride levels Avoid combination or reduce glimepiride dose by 50%; intensive glucose monitoring

Rifampicin Reduced glycaemic efficacy CYP2C9 induction → increased glimepiride clearance May need to increase glimepiride dose or switch to alternative antidiabetic during TB treatment

Beta-blockers (non-selective) Masked hypoglycaemia symptoms Block adrenergic warning signs (except sweating) Prefer cardioselective beta-blockers; educate patient on atypical symptoms

Warfarin Enhanced hypoglycaemia + altered anticoagulation Protein binding displacement Monitor INR and glucose closely

Sulfonamide antibiotics (e.g., Cotrimoxazole) Severe hypoglycaemia CYP2C9 inhibition + protein displacement Avoid if possible; close glucose monitoring if used

Interacting Drug Effect Management

ACE inhibitors / ARBs May enhance hypoglycaemic effect Monitor glucose; may need dose reduction

NSAIDs (ibuprofen, diclofenac) Increased hypoglycaemia risk Protein displacement; monitor glucose

Pioglitazone Additive hypoglycaemia + weight gain Monitor weight and glucose; may need to reduce glimepiride

Isoniazid May reduce sulfonylurea efficacy Monitor HbA1c; adjust dose as needed

Glucocorticoids Antagonise glucose-lowering effect Monitor FPG/PPG; may need temporary dose increase or insulin

Thiazide diuretics May worsen glycaemic control Monitor glucose; adjust antidiabetic therapy

Alcohol Unpredictable glucose effects; disulfiram-like reaction rare Advise moderation; monitor glucose

Clarithromycin / Erythromycin May increase glimepiride levels CYP3A4 inhibition (minor pathway); monitor glucose

• Hypoglycaemia (dose-dependent; most common)

• Weight gain (1–3 kg typical over first year)

• Nausea, epigastric discomfort

• Headache

• Dizziness

• Photosensitivity rash

• Mild gastrointestinal upset

Adverse Effect Notes

Severe/prolonged hypoglycaemia May require IV dextrose infusion and hospitalisation; can persist >24 hours especially in elderly/renal impairment

Cholestatic jaundice Rare; discontinue immediately; monitor LFTs

Stevens-Johnson syndrome / TEN Rare hypersensitivity; immediate discontinuation required

Haemolytic anaemia Rare; especially in G6PD deficiency

Thrombocytopenia / Agranulocytosis Rare; monitor if unexplained bleeding or infections

Hyponatraemia (SIADH) Rare; reported with sulfonylureas

Common FDC Brands:

NPPA Status: Glimepiride included in NLEM 2022; FDCs with metformin under price control.

Government Supply: Available through public health facilities and Jan Aushadhi stores at subsidised rates.

1. Patient selection matters: Best suited for lean, non-obese T2DM patients with preserved beta-cell function; avoid in overweight patients where metformin, SGLT2 inhibitors, or GLP-1 agonists offer metabolic advantages.

1. Start low, go slow: Most Indian patients respond to 1–2 mg/day; dose escalation beyond 4 mg rarely provides additional benefit and increases hypoglycaemia risk.

1. Meal timing is critical: Always counsel patients to take with breakfast and never skip meals; avoid use in shift workers or those with erratic eating patterns.

1. Hypoglycaemia education is essential: Teach patients and caregivers to recognise symptoms and carry glucose tablets/sweets; ensure contact numbers for emergencies.

1. Reassess at 3 months: If HbA1c not improving despite adequate dose (4 mg) and compliance, reconsider diagnosis (LADA, secondary diabetes) or switch drug class rather than escalating further.

1. Perioperative and sick-day management: Temporarily switch to insulin during acute illness, surgery, or fasting states to avoid hypoglycaemia or uncontrolled hyperglycaemia.

type 2 diabetes; sulfonylurea; hypoglycaemia risk; elderly-caution; renal-dose-adjust; hepatic-caution; once-daily; insulin-secretagogue; NLEM India; endocrinology

RxIndia v1.1 — 09 Jul 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• National List of Essential Medicines (NLEM 2022)

• API Textbook of Medicine (11th Edition)

• ICMR Guidelines for Management of Type 2 Diabetes (2022)

• AIIMS Diabetes Treatment Protocols

• IAP Guidelines for Paediatric Diabetes

• Product inserts: Amaryl® (Sanofi), Glimy® (USV)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics