Effect of Concurrent Metformin on Adherence to and Persistence of Treatment With Second-Generation Antipsychotics in Nondiabetic Patients

Jerusha Daggolu, MD; Hua Chen, MD, PhD

J Clin Psychiatry 2026;87(1):25m15808

Abstract

Objective: Second-generation antipsychotic (SGA)-induced weight gain (AIWG) is a major factor contributing to SGA nonadherence. The aim of the study was to evaluate the effect of concurrent metformin treatment on SGA adherence and persistence.

Methods: A retrospective cohort study using MarketScan Commercial and Medicaid claims data included nondiabetic adults (≥18 years) with ≥30 days of overlapping prescriptions for SGAs and metformin. SGA-metformin concurrent users were 1:4 matched to SGA-only users and followed for 180 and 365 days to assess SGA adherence using proportion of days covered (PDC) and persistence (days until a 60-day gap). Additionally, concurrent users were classified into early (<30 days) and delayed (≥30 days) initiators based on the duration between SGA and metformin initiation. The differences between study groups were adjusted by propensity score using inverse probability of treatment weights (IPTW).

Results: In commercially insured patients, 575 concurrent users were matched to 2,300 SGA-only users, whereas Medicaid had 972 concurrent users matched to 3,888 SGA-only users. During the 180-day follow-up period, concurrent users demonstrated higher PDC and persistence to SGA than SGA-only users (PDC: commercial: 80.9% vs. 67.61%; Medicaid: 78.41% vs 68.27%; persistence: commercial: 139.0 vs 106.4 days; Medicaid: 149.1 vs 115.7 days). After IPTW adjustment, the differences in PDC between the study groups were 11.79% (commercial) and 9.64% (Medicaid), with corresponding differences in persistence of 32.14 (commercial) and 33.78 (Medicaid) days. The findings for the early and delayed initiators and the 365-day follow-up period were consistent with the main analysis.

Conclusion: The concurrent use of metformin with SGA drugs was associated with improved adherence and persistence to SGAs at both 180-and 365-day follow-up periods in adults with Medicaid and commercial insurance. Additionally, the observed improvement in SGA adherence among both early and delayed metformin initiators supports the effectiveness of metformin in enhancing adherence, whether used on a preventive basis or as a treatment for AIWG.

J Clin Psychiatry 2026;87(1):25m15808
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