Drug reference

Metformin

Biguanide · Antidiabetic

Also known as Metformin hydrochloride, Glucomin, Glyciphage, Met XL, Glycomet, Riomet

START

500 mg PO BID with meals

TYPICAL MAX

2,000 mg/day (typical) · 2,550 mg/day (IR ceiling)

STOP IF

eGFR <30 mL/min/1.73m²

WATCH

Lactic acidosis · B12 deficiency

CDSCO approvedSchedule HJan AushadhiNPPA price-controlledATC A10BA02

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1h · GI absorption begins
PEAK: 2.5h · Cmax (IR)
t½: 6.2h · plasma t½
DURATION: 12h · IR clinical effect

EXCRETION

90% renal unchanged · no CYP metabolism

route + CYP

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

Category B — preferred over sulfonylureas in GDM

FDA category + note

Top interactionssee all 12 →

Tyrosine Kinase InhibitorsSevereTextbookG&G 14e · p82
AcetazolamideSevereDatabaseDDInter
DiatrizoateSevereDatabaseDDInter
DiclofenamideSevereDatabaseDDInter

Available in India

684 branded formulations and 6,800 fixed-dose combinations. Look up specific brands in the Drugs workspace.

Jan Aushadhi — generic available at GoI pharmacies

Mechanism

Metformin reduces hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis, primarily by activating AMP-activated protein kinase (AMPK). It also improves insulin sensitivity in peripheral tissues (skeletal muscle and adipose tissue), leading to increased glucose uptake and utilization. Additionally, it delays intestinal glucose absorption, contributing to its glucose-lowering effects without causing hypoglycemia.

Indications

Type 2 Diabetes Mellitus (as monotherapy or in combination)Gestational Diabetes (off-label)Polycystic Ovary Syndrome (PCOS) (off-label)Type 2 diabetes mellitusMitigate antipsychotic-induced weight gain (olanzapine, clozapine)mitigate lithium-related weight gainmitigate SGA-induced weight gain in child/adolescent patientsFirst-line treatment of type 2 diabetesInfertility in women with polycystic ovarian syndrome (off-label)Delay progression to diabetes in impaired glucose tolerancetype 2 diabetes mellitus (first choice)improve ovulation and fertility in women with polycystic ovary syndrome

Dosing

Adult: Initial: 500 mg orally once daily or twice daily with meals. Titration: Increase by 500 mg weekly to a maximum of 2550 mg/day (immediate-release; FDA GLUCOPHAGE label). For extended-release (XR): Initial 500-1000 mg once daily with evening meal; increase by 500 mg weekly to a maximum of 2000 mg/day.
Pediatric: (10-16 years): Initial: 500 mg orally twice daily with meals. Titration: Increase by 500 mg weekly to a maximum of 2000 mg/day in divided doses.
Renal adjustment: eGFR ≥45 mL/min/1.73m²: No renal dose restriction — metformin may be initiated and continued at standard dose (up to 2000 mg/day). eGFR 30-44 mL/min/1.73m²: Do not initiate; if the patient is already on metformin, reduce to a maximum of 1000 mg/day and monitor renal function every 3 months. eGFR <30 mL/min/1.73m²: Contraindicated — discontinue.
Hepatic adjustment: Contraindicated in severe hepatic impairment due to increased risk of lactic acidosis. Use with caution in moderate impairment; monitor liver function closely.
Geriatric: Monitor renal function closely (eGFR) as elderly patients are more prone to renal impairment. Start with lower doses (e.g., 500 mg once daily) and titrate slowly.
Max dose: 2550 mg/day (immediate-release) or 2000 mg/day (extended-release).

Pharmacokinetics

Onset

Glucose-lowering effects typically observed within a few days.

Peak effect

Immediate-release: 2-3 hours; Extended-release: 4-8 hours.

Duration

Immediate-release: Approximately 10-12 hours.

Half-life

Plasma elimination half-life is approximately 4-9 hours (single dose), but blood half-life is approximately 17 hours.

Bioavailability

Approximately 50-60% after oral administration in a fasting state.

Protein binding

Negligible (<5%).

Metabolism

Not metabolized in the liver. Excreted unchanged.

Excretion

Primarily renal excretion (unchanged drug).

Contraindications

Severe renal impairment (eGFR <30 mL/min/1.73m²)
Acute or chronic metabolic acidosis, including diabetic ketoacidosis
Known hypersensitivity to metformin
Severe congestive heart failure requiring pharmacological treatment
Severe hepatic impairment
Acute myocardial infarction
Severe infection/sepsis
Dehydration
Radiological studies involving intravascular administration of iodinated contrast media (temporarily discontinue)
hypotensive states
heart failure
severe respiratory disease
hepatic disease
renal disease
alcoholics

Side effects

Common

DiarrheaNauseaVomitingAbdominal painFlatulenceAnorexiaMetallic tasteHeadacheWeaknessIndigestionAbdominal crampsBloatingVitamin B12 deficiencymild diarrhoeatirednessvitamin B12 deficiency (with high dose)

Serious

Lactic acidosis (rare but serious)
Vitamin B12 deficiency (with long-term use)
Hypoglycemia (when combined with insulin or sulfonylureas)
Lactic acidosis
lactic acidosis (accentuated in liver disease)
lactic acidosis (rare, increased risk with alcohol or renal failure)

Pregnancy & lactation

Pregnancy

Category B — preferred over sulfonylureas in GDM

Lactation

Metformin is excreted into breast milk in small amounts. It is generally considered compatible with breastfeeding, but caution is advised, and the infant should be monitored for adverse effects.

Drug interactions

Tyrosine Kinase Inhibitors

Severe

Textbook

Enhances biguanide toxicity, potentially leading to lactic acidosis, a lethal side effect.

Caution should be exercised when co-administering metformin with tyrosine kinase inhibitors, and patients should be monitored for signs of metformin toxicity.

Source: G&G 14e · p82

Acetazolamide

Severe

Database

Drug interaction classified as: synergy.

Source: DDInter

Diatrizoate

Severe

Database

Clinical effect not specified

Source: DDInter

Diclofenamide