Metformin

Uses

• Type 2 diabetes mellitus (adults and some adolescents): First-line therapy to improve glycaemic control when diet and exercise are insufficient. Effective as monotherapy or in combination with other antihyperglycaemics, including fixed-dose combinations (e.g., metformin + sitagliptin; metformin + empagliflozin; metformin + vildagliptin; metformin + saxagliptin; metformin + linagliptin; metformin + dulaglutide in co-pack schemes).
• Pre-diabetes / impaired glucose regulation (selected patients): In individuals at very high risk of progression to diabetes (e.g., younger adults with obesity, prior gestational diabetes, or worsening glycaemia despite lifestyle measures), some clinicians consider metformin off-label after risk–benefit discussion; lifestyle modification remains cornerstone.
• Polycystic ovary syndrome (PCOS): Off-label in many EU countries to address insulin resistance, improve menstrual regularity/ovulation, and support weight and metabolic health, often adjunctive to lifestyle measures; fertility and pregnancy planning require specialist oversight.

How to take (typical EU practice—follow local SmPC)

• Start low, go slow: e.g., IR 500 mg once daily with the largest meal for 3–7 days, then 500 mg twice daily; titrate by 500 mg increments weekly as tolerated. Many adults target 1,500–2,000 mg/day; maximum 3,000 mg/day (varies by brand/country). For MR/XR, start 500–750 mg once daily with the evening meal; titrate every 1–2 weeks.
• With food: Always take with meals to reduce GI side effects. Swallow MR/XR tablets whole—do not crush or chew.
• Renal function guides dosing: Use eGFR (mL/min/1.73 m²). See Warnings for thresholds and adjustments.
• Adherence matters: Regular daily dosing is required to maintain HbA1c reductions. Missing doses reduces control.

Clinicians typically recheck HbA1c at ~3 months after initiation/titration. If targets are not met, options include further titration, switching to MR, or adding another class (GLP-1 RA or SGLT2 inhibitor often preferred when weight loss or cardiorenal benefit is needed).

Side Effects

Metformin’s safety profile is well established. The majority of adverse effects are gastrointestinal and dose-dependent, usually transient with gradual titration. Serious events are uncommon with appropriate patient selection.

Very common/Common

• Gastrointestinal: nausea, abdominal discomfort/cramping, early satiety, metallic taste, diarrhoea, flatulence. Strategies: start low, take with meals, use MR/XR formulation, slow titration. Temporary dose reduction often helps.
• Appetite reduction/weight effects: modest weight loss or weight neutrality is typical (beneficial for many patients).

Uncommon

• Vitamin B₁₂ reduction: with long-term therapy; may present as anaemia, neuropathy, cognitive changes. Consider periodic B₁₂ checks in those with risk factors (vegan diets, malabsorption, metformin >3–4 years, neuropathy symptoms). Supplement as appropriate.
• Skin reactions: rash, pruritus (rare; usually mild).

Rare/Very rare—seek urgent care

• Lactic acidosis: Presents with malaise, myalgias, respiratory distress, abdominal pain, somnolence, hypothermia, hypotension; laboratory features include elevated lactate, high anion-gap metabolic acidosis. Risk factors include severe renal impairment, hypoxic states (cardiorespiratory failure, shock, sepsis), severe hepatic disease, excessive alcohol intake, dehydration, and concomitant contrast studies without proper precautions. Incidence is very low when SmPC contraindications/precautions are followed.
• Hepatic dysfunction: rare idiosyncratic hepatitis reported; discontinue if suspected.

Hypoglycaemia: Metformin alone rarely causes hypoglycaemia. The risk increases when combined with insulin or insulin secretagogues (e.g., sulfonylureas); in combined therapy, counsel on recognition and management of hypoglycaemia.

Warnings & Precautions

• Renal function (use eGFR):
  • eGFR ≥60: standard dosing; monitor renal function at least annually.
  • eGFR 45–59: continue/initiate with caution; consider dose reduction and monitor every 3–6 months.
  • eGFR 30–44: initiation generally not recommended; if continuing, use reduced dose with close monitoring and reassess risks/benefits frequently.
  • eGFR <30: contraindicated.
• Iodinated contrast procedures (CT angiography, etc.): Withhold metformin at or before the time of the procedure in patients with eGFR 30–59, history of liver disease, alcoholism, or heart failure, or if intra-arterial contrast is used; reassess eGFR 48 hours after and restart only if stable and adequate.
• Surgery/acute illness: Consider temporary discontinuation during periods of restricted intake, severe infection, dehydration, hypoxia, or haemodynamic instability to reduce lactic acidosis risk; restart when clinically stable and eating/drinking normally.
• Hepatic impairment: Avoid in severe hepatic disease due to lactic acidosis risk.
• Alcohol: Excessive acute or chronic alcohol intake increases lactic acidosis risk; advise moderation and avoidance of binge drinking.
• Pregnancy and breastfeeding: Insulin is often preferred for glycaemic control during pregnancy; metformin may be used in selected cases under specialist advice (e.g., some PCOS and gestational diabetes scenarios). Metformin appears in breast milk in low amounts; discuss risks/benefits with a clinician.
• Older adults/frailty: Renal function declines with age; monitor eGFR more frequently. Use conservative doses.
• Vitamin B₁₂ monitoring: Consider periodic measurement, especially with anaemia/neuropathy symptoms, long duration, or risk factors.

Patients should receive sick-day guidance: maintain hydration, monitor blood glucose more closely, and seek advice early if vomiting, diarrhoea, or fever lead to reduced intake; temporary dose interruption may be advised.