metformin

General Information

Metformin (brand Glucophage; many generics) is a biguanide used for type 2 diabetes. In psychiatry it is commonly used off label to mitigate antipsychotic-associated weight gain and metabolic risk (clinical).

It is generally weight-neutral to modestly weight-lowering and does not typically cause hypoglycemia as monotherapy; GI tolerability and kidney function drive most practical decisions (label/clinical).

The key rare but serious adverse event is lactic acidosis, which is strongly associated with renal dysfunction and other hypoxic states; baseline and periodic kidney-function review is central to safety planning (label).

Evidence syntheses support modest average weight loss and improved metabolic markers in antipsychotic-treated populations, especially when started early after weight gain begins (Wu 2008; Lee 2011).

The metformin compare view, evidence feed, and print page support counseling and coordination with primary care when metabolic adverse effects are driving regimen changes.

In psychiatric practice, metformin is often considered when metabolic monitoring shows weight gain, impaired glucose tolerance, or developing metabolic syndrome during antipsychotic treatment. It is typically used alongside lifestyle interventions and, when feasible, antipsychotic dose/agent adjustments rather than as a stand-alone strategy (clinical).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Biguanide antihyperglycemic that reduces hepatic gluconeogenesis and improves peripheral insulin sensitivity (mechanism).

It does not stimulate insulin secretion, so hypoglycemia is uncommon unless combined with insulin or insulin secretagogues (label/clinical).

• Biguanide antihyperglycemic (insulin sensitizer; reduced hepatic glucose output).

Metabolism and Pharmacokinetics

• Metformin is not metabolized and is eliminated unchanged in urine via glomerular filtration and active tubular secretion (label).
• After oral administration, ~90% of absorbed drug is eliminated by the renal route within the first 24 hours (label).
• Plasma elimination half-life is ~6.2 hours and blood half-life ~17.6 hours; steady-state is generally reached within 24–48 hours at usual dosing schedules (label).
• In renal impairment, clearance decreases and half-life is prolonged, increasing exposure and lactic acidosis risk (label).

Dosing and Administration

• Label initiation commonly starts at 500 mg once or twice daily with meals, then increases in weekly steps as tolerated; total daily maximum varies by formulation/manufacturer (label).
• Extended-release formulations are often taken with the evening meal and should not be crushed unless the product allows (label).
• Off label for antipsychotic-associated weight gain: common targets are 1,000–2,000 mg/day with gradual titration as tolerated, typically paired with diet/activity counseling and metabolic monitoring (Wu 2008; Lee 2011).
• For iodinated contrast studies, metformin may be held in higher-risk contexts and restarted after renal function is reassessed per label guidance (label).

Monitoring & Labs

• Baseline and periodic renal function (eGFR/creatinine) to guide dosing and continuation (label).
• Metabolic monitoring (weight, waist circumference, fasting glucose/A1c, lipids) integrated with antipsychotic monitoring workflows (clinical).
• Vitamin B12 level assessment when symptoms or prolonged treatment suggests deficiency (label/clinical).
• Review for high-risk contexts for lactic acidosis (dehydration, sepsis, hypoxemia, heavy alcohol use) and pause therapy during acute illness when risk rises (label/clinical).

Metformin is often best coordinated with primary care/endocrinology when diabetes or prediabetes is present, especially when renal function or contrast imaging is in play (clinical).

Adverse Effects

Interactions

• Iodinated contrast can precipitate acute kidney injury; per label, metformin is held in patients with reduced eGFR or other risk factors and restarted after renal function is reassessed (label).
• Cationic drugs cleared by renal tubular secretion (e.g., cimetidine, some OCT2/MATE inhibitors) can increase metformin exposure; monitor when these are added or stopped (label).
• Alcohol increases lactic acidosis risk; avoid excessive intake and consider alcohol-use screening when risk is elevated (label/clinical).
• Carbonic anhydrase inhibitors (e.g., topiramate) can increase metabolic acidosis risk; consider alternatives or closer monitoring in higher-risk patients (label/clinical).

Other Useful Information

• In antipsychotic-treated populations, metformin has evidence for modest mean weight loss and improvements in metabolic markers, with larger benefit when started soon after weight gain begins (Wu 2008; Lee 2011).
• Antipsychotic selection and dose strategies still matter: switching to a lower metabolic-risk antipsychotic or using other mitigation strategies may be considered when psychiatric stability allows (clinical).
• Because metformin is often co-managed across psychiatry and primary care, aligning targets (weight, A1c/glucose, lipids) and monitoring cadence can reduce duplicated labs and missed abnormalities (clinical).

References

1. Metformin hydrochloride tablets prescribing information — DailyMed (2025)
2. Lifestyle Intervention AND Metformin FOR Treatment OF Antipsychotic Induced Weight Gain — JAMA (2008)
3. A systematic review of metformin to limit weight gain with atypical antipsychotics — Journal of Clinical Pharmacy and Therapeutics (2011)
4. Efficacy OF Metformin AND Topiramate IN Prevention AND Treatment OF Second Generation Antipsychotic–induced Weight Gain — The Annals of Pharmacotherapy (2010)
5. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)