A recent retrospective cohort study examined whether adding metformin to second-generation antipsychotic (SGA) therapy improves medication adherence in nondiabetic adults; a critical question given that antipsychotic-induced weight gain is a major driver of nonadherence.

Using 2017–2019 commercial and Medicaid claims data, the investigators matched SGA–metformin users to SGA-only users and measured treatment adherence and persistence over 180 and 365 days, adjusting for differences between groups with inverse probability weighting. Across both insurance groups, patients receiving concurrent metformin demonstrated significantly better adherence to their SGAs. In the commercial cohort, mean proportion of days covered (PDC) was 80.9% in metformin users versus 67.6% in SGA-only users, while Medicaid patients showed a similar improvement (78.4% vs 68.3%).

Persistence was also substantially higher, with metformin users remaining on antipsychotic treatment 32–34 days longer on average. Importantly, these effects were consistent whether metformin was initiated early (within 30 days of starting the SGA) or later, suggesting benefit both for preventing and treating antipsychotic-related weight gain.

The advantages also persisted in one-year follow-up and across sensitivity analyses involving specific antipsychotics. Overall, the findings indicate that concurrent metformin use is associated with meaningfully improved SGA adherence and persistence in nondiabetic patients, supporting its role as a potentially valuable adjunct in managing metabolic side effects and enhancing long-term treatment continuity.

Reference:

Daggolu J, Chen H. J Clin Psychiatry. 2025;87(1):25m15808. Abstract