metformin

Adjunctive therapy

Brands: Glucophage, Glucophage XR, Fortamet, Glumetza

Last reviewed 2025-12-30

Reviewed by PsychMed Editorial Team.

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Quick answers

What is metformin?
Metformin (brand Glucophage; many generics) is a biguanide used for type 2 diabetes. In psychiatry it is commonly used off label to help mitigate weight gain and metabolic risk from second-generation antipsychotic (SGA) treatment (clinical).
What is Glucophage?
Glucophage is a brand name for metformin (other brands: Glucophage XR, Fortamet, Glumetza).
What is Glucophage (metformin) used for?
Label indications include: Type 2 diabetes mellitus; adjunct to diet and exercise for glycemic control (label). Common off-label use includes mitigation of antipsychotic-associated weight gain and metabolic risk (clinical).
What drug class is Glucophage (metformin)?
Biguanide antihyperglycemic that reduces hepatic glucose production and improves insulin sensitivity; does not typically cause hypoglycemia as monotherapy. In psychiatry it is commonly used off label to help mitigate antipsychotic-associated weight gain and metabolic risk.
What strengths does Glucophage (metformin) come in?
Immediate-release tablets: 500 mg, 850 mg, 1000 mg; oral solution exists (label/manufacturer-dependent).

Snapshot

Primary label indications include: Type 2 diabetes mellitus; adjunct to diet and exercise for glycemic control (label).
Class: Adjunctive therapy
Common US brands: Glucophage, Glucophage XR, Fortamet, Glumetza
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2025-12-30

Label indications

Type 2 diabetes mellitus; adjunct to diet and exercise for glycemic control (label). Common off-label use includes mitigation of antipsychotic-associated weight gain and metabolic risk (clinical).

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Clinical Highlights

Metformin (brand Glucophage; many generics) is a biguanide used for type 2 diabetes. In psychiatry it is commonly used off label to help mitigate weight gain and metabolic risk from second-generation antipsychotic (SGA) treatment (clinical). It is generally weight-neutral to modestly weight-lowering and does not typically cause hypoglycemia as monotherapy, which is one reason it is often the first medication adjunct considered when antipsychotic-related weight gain or impaired glucose tolerance emerges (label/clinical).

The most common adverse effects are gastrointestinal (diarrhea, nausea, abdominal discomfort), especially during initiation; slow titration and taking doses with meals often improves tolerability (label/clinical).
The major rare but serious risk is lactic acidosis, which is strongly associated with renal dysfunction and other hypoxic states; baseline and periodic kidney function review is central to safe use (label).
The compare view, metformin evidence feed, and metformin print page support shared decision-making when metabolic adverse effects are driving regimen changes.

Dosing & Formulations

Immediate-release tablets: 500 mg, 850 mg, 1000 mg; extended-release tablets and oral solution exist (label/manufacturer-dependent). Label titration for type 2 diabetes commonly starts at 500 mg once or twice daily with meals, then increases in weekly steps as tolerated; GI tolerability often determines pace (label).

In antipsychotic-associated weight-gain trials, metformin is commonly titrated toward 1,000–2,000 mg/day (for example, 500 mg twice daily as tolerated), typically alongside diet and activity counseling (Wu 2008/clinical).
Extended-release formulations can reduce GI adverse effects for some patients and are often taken with the evening meal; tablets should not be crushed unless the product allows (label/clinical).

Monitoring & Risks

Kidney function is the primary safety gate: metformin is cleared renally and accumulates in renal impairment; dose and continuation decisions track eGFR/creatinine clearance (label). Vitamin B12 deficiency can occur with longer-term use; clinicians often recheck B12 when anemia, neuropathy, or cognitive symptoms emerge (label/clinical).

Lactic acidosis is rare but life-threatening; higher-risk contexts include severe renal impairment, sepsis, dehydration, shock, or hypoxemia, and heavy alcohol use (label).
GI effects (diarrhea, nausea, abdominal discomfort) are common early and often improve; slower titration and meal timing are common mitigations (label/clinical).

Drug Interactions

Iodinated contrast can precipitate acute kidney injury; temporary metformin holding around contrast studies is standard in higher-risk patients per label guidance (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, especially with binge use or liver disease; counseling and screening for hazardous alcohol use are common (label/clinical).
Carbonic anhydrase inhibitors (including topiramate) can increase metabolic acidosis risk; combined use may warrant closer monitoring or alternative selection when risk is high (label/clinical).

Practice Notes

When weight gain is driven by antipsychotics, nonpharmacologic steps (dietary counseling, sleep, activity, and metabolic monitoring) remain foundational; metformin is typically framed as an adjunct, not a replacement (clinical). Evidence syntheses suggest metformin produces modest mean weight loss and metabolic improvements in antipsychotic-treated patients, with the largest benefit when started soon after weight gain begins (Lee 2011; Ellinger 2010).

Metformin is not labeled for antipsychotic-associated weight gain; documentation often clarifies the off-label goal and the monitoring plan (clinical).

References

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