Antipsychotic-induced weight gain remains a significant challenge in psychiatric practice, contributing to metabolic syndrome, decreased quality of life, and reduced medication adherence. This issue is especially concerning given the chronic nature of psychiatric illnesses requiring antipsychotic treatment. Among strategies to address this, metformin—an insulin sensitizer primarily used for type 2 diabetes—has garnered considerable interest. Below, we summarize the evidence from randomized controlled trials (RCTs) evaluating metformin’s efficacy and safety in mitigating weight gain associated with antipsychotic medications.
Evidence from Randomized Controlled Trials
- Meta-Analyses and Systematic Reviews
- Multiple meta-analyses of RCTs have shown that metformin effectively reduces weight gain in individuals receiving antipsychotics. Weight reductions of 2-3 kg over 12-16 weeks have been reported compared to placebo.
- Beyond weight loss, improvements in metabolic parameters such as fasting glucose, insulin resistance, and lipid profiles have been observed.
- Population-Specific Findings
- First-Episode Psychosis (FEP): Studies indicate that metformin is particularly effective in individuals with FEP who experience rapid weight gain shortly after initiating antipsychotic therapy. Early intervention appears to yield more substantial benefits.
- Chronic Schizophrenia: RCTs in populations with chronic schizophrenia have demonstrated similar weight-reducing effects, though results may be less pronounced compared to FEP patients.
- Adjunctive Lifestyle Interventions
- Combining metformin with lifestyle interventions, such as diet and exercise counseling, results in synergistic benefits. RCTs demonstrate that this combination is more effective than metformin or lifestyle changes alone.
Safety and Tolerability
Metformin is generally well-tolerated. The most common side effects are gastrointestinal (e.g., nausea, diarrhea), which tend to subside with continued use. Rarely, lactic acidosis—a serious adverse event—can occur, particularly in individuals with renal impairment. It is crucial to monitor kidney function periodically.
Practical Considerations
- Dosing: Initiate metformin at a low dose (e.g., 500 mg once daily) to minimize gastrointestinal side effects, and titrate gradually to a typical maintenance dose of 1,000-2,000 mg per day.
- Monitoring: Regularly assess weight, BMI, fasting glucose, and lipid profiles. Monitor renal function before and during treatment.
- Patient Selection: Metformin may be particularly beneficial for patients who:
- Have significant weight gain or metabolic disturbances from antipsychotic use.
- Are early in their antipsychotic treatment course.
- Have no contraindications, such as severe renal impairment.
Conclusion
Metformin offers a promising strategy for mitigating antipsychotic-induced weight gain, supported by robust evidence from RCTs. While not a standalone solution, it can play a critical role in a comprehensive approach to managing the metabolic side effects of antipsychotics. Clinicians should consider metformin’s inclusion in treatment plans for patients struggling with weight gain or metabolic dysfunction related to antipsychotic treatment.
