A NEW trial has revealed that metformin can modestly but meaningfully reduce weight gain in young people treated with second generation antipsychotics, offering clinicians a valuable tool for protecting long-term health.
Why Weight Matters in Bipolar Treatment with Metformin
Second generation antipsychotics remain central to managing mood instability in bipolar spectrum disorders, yet they frequently trigger substantial weight gain and metabolic disruption. These effects increase long-term risks of cardiovascular disease, particularly in young people who are overweight or obese. Metformin has been found effective in mitigating such weight changes, but until now it had not been studied over extended periods or in everyday clinical environments. This trial set out to determine whether metformin could reliably support healthier outcomes in typical treatment settings.
Large Scale Trial Shows Metformin Improves BMI Outcomes
In a multi-site, open label parallel group study across 64 US clinical sites, 1565 participants aged 8 to 19 years were randomly assigned in a 1:1 ratio to either healthy lifestyle guidance (LIFE) or metformin plus LIFE (MET plus LIFE). Co primary outcomes measured change in BMI Z score at 6 and 24 months. After 6 months, the MET plus LIFE group demonstrated a standardised effect size of 0.26 (95 percent CI 0.15 to 0.37, p<0.0001). At 24 months, the effect size was 0.11 (0.00 to 0.22, p=0.047). Gastrointestinal adverse events were 2 to 4 times more common in those taking metformin, while suicidality rates did not differ significantly between groups. The mean age of participants was 13.9 years, and data from more than 1200 individuals at each time point strengthened the reliability of these findings.
Clinical Implications and Future Considerations for Metformin
The results suggest that metformin should be considered a practical adjunct for young people receiving second-generation antipsychotics who are overweight or obese. Its modest but consistent impact on BMI may help reduce cumulative cardiometabolic risk across adolescence. Future clinical guidance may focus on tailoring metformin use to patients most vulnerable to antipsychotic-related weight gain and refining strategies to minimise gastrointestinal side effects while maintaining long-term metabolic protection.
Reference
DelBello MP et al. Metformin for overweight and obese children and adolescents with bipolar spectrum and related mood disorders treated with second-generation antipsychotics: a randomised, pragmatic trial. The Lancet Psychiatry. 2025;12(12):893-905.
