A fixed-dose combination (FDC) oral anti-diabetic drug containing a second-generation sulfonylurea (Gliclazide) and a biguanide (Metformin). It is a cornerstone therapy for the management of Type 2 Diabetes Mellitus (T2DM) in Indian patients, particularly those not adequately controlled on monotherapy with either agent. Gliclazide stimulates insulin secretion from pancreatic beta-cells, while Metformin primarily reduces hepatic glucose production and improves insulin sensitivity. This combination provides a synergistic, multi-targeted approach to glycemic control.
Adult: Usually one tablet (Gliclazide 80mg + Metformin 500mg) twice daily, with or just after breakfast and dinner. Dose must be individualized based on glycemic response. Maximum: Two tablets twice daily (i.e., Gliclazide 320mg + Metformin 2000mg per day). Initiation with lower dose (e.g., once daily) is recommended in some patients.
Note: Take with meals to reduce gastrointestinal side effects from Metformin. Swallow whole with a glass of water; do not crush or chew. Maintain regular meal patterns to avoid hypoglycemia. Dose timing should be consistent with major meals.
The combination works via complementary mechanisms. Gliclazide binds to sulfonylurea receptors (SUR1) on pancreatic beta-cell membranes, leading to closure of ATP-sensitive potassium (K-ATP) channels, membrane depolarization, opening of voltage-gated calcium channels, and subsequent exocytosis of insulin. Metformin's primary action is to decrease hepatic gluconeogenesis and glycogenolysis. It also increases peripheral glucose uptake and utilization (insulin sensitization) in muscles and adipose tissue, and may delay intestinal glucose absorption.
Pregnancy: Pregnancy Category C/D (varies by region). Insulin is the preferred treatment for diabetes in pregnancy. This combination is not recommended. Gliclazide may cross the placenta and cause neonatal hypoglycemia. Metformin is sometimes used in gestational diabetes but not in combination with sulfonylureas as first-line.
Driving: Patients should be cautioned about the risk of hypoglycemia, which can impair concentration and reaction time. Advise to check blood glucose before driving and to carry a fast-acting carbohydrate source.
| Other Anti-diabetics (Insulin, Thiazolidinediones) | Increased risk of hypoglycemia | Major |
| Beta-blockers (e.g., Propranolol) | Masked hypoglycemic symptoms (tachycardia); may potentiate hypoglycemia | Moderate |
| Alcohol | Increased risk of lactic acidosis (Metformin); potentiation of hypoglycemic effect; disulfiram-like reaction (Gliclazide) | Major |
| Warfarin | Gliclazide may potentiate anticoagulant effect | Moderate |
| CYP2C9 Inhibitors (e.g., Fluconazole, Amiodarone, Sulfinpyrazone) | Increased Gliclazide plasma levels → hypoglycemia risk | Moderate |
| CYP2C9 Inducers (e.g., Rifampicin, Carbamazepine) | Decreased Gliclazide plasma levels → hyperglycemia | Moderate |
| Cationic Drugs (e.g., Cimetidine, Ranitidine, Digoxin, Amiloride) | Competition for renal tubular secretion → increased Metformin levels | Moderate |
| Diuretics (especially Loop and Thiazide) | May cause hyperglycemia; risk of lactic acidosis with Metformin if dehydration occurs | Moderate |
| Corticosteroids (e.g., Prednisolone) | Decreased hypoglycemic effect → hyperglycemia | Major |
| NSAIDs (e.g., Ibuprofen) | May potentiate hypoglycemic effect of sulfonylureas | Moderate |
Same composition (Gliclazide (80mg) + Metformin (500mg)), different brands: