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. 2025 Aug 15.
doi: 10.1038/s41366-025-01885-4. Online ahead of print.

Weight change from incretin-based weight loss medications across categories of second-generation antipsychotics

Jithin Sam Varghese  1   2 , David R Goldsmith  3 , Robert O Cotes  3 , Vishnu Ravikumar  4 , Mohammed K Ali  5   6   7 , Francisco J Pasquel  5   6   8
Affiliations

Weight change from incretin-based weight loss medications across categories of second-generation antipsychotics

Jithin Sam Varghese et al. Int J Obes (Lond). .

Abstract

Objective: Patients prescribed second-generation antipsychotics (SGA) are at risk of antipsychotic induced weight gain (AIWG). The objective was to estimate weight changes after prescription of incretin-based weight loss medications by category of expected AIWG: high (olanzapine, clozapine), intermediate (risperidone, quetiapine, paliperidone) and low (e.g., asenapine, aripiprazole).

Methods: We conducted a retrospective cohort study using electronic health records (June 2021-December 2023) from Epic Cosmos for adults (≥18 years) without diabetes, prescribed SGA, and eligible for incretin-based weight loss medications. We studied changes in weight (kg) and the probability of at least 5% weight loss after 6 months of prescription of incretin-based medications by categories of AIWG.

Results: The analytic sample (n = 66,574) were aged 51.9 years (SD: 17.7), with average BMI of 39.5 kg/m2 (SD: 7.7). Those prescribed incretin-based medications lost -2.17 kg (95% CI: -2.49, -1.84), and were 1.71 (95% CI: 1.63, 1.80) times more likely to achieve 5% weight loss, relative to those who didn't receive prescriptions. Weight loss was greater among those prescribed SGAs of low AIWG (-3.02 kg, 95% CI: -3.29, -2.74), relative to those prescribed high AIWG (-1.33 kg, 95% CI: -2.04, -0.62).

Conclusions: Semaglutide and tirzepatide induce weight loss among those prescribed SGAs, with lower effectiveness in those prescribed higher AIWG SGAs.

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Conflict of interest statement

Competing interests: ROC has received research funding (to institution) from Otsuka, Karuna, Roche, and Alkermes. He is a consultant to IQVIA, Boehringer Ingelheim, and Syneos Health on behalf of the Clozapine Product Manufacturers Group. He is a speaker and consultant to Saladax Biomedical. MKA has served as a consultant for Eli Lilly. FJP has received research support through his institution from Dexcom, Tandem, Insulet, Novo Nordisk, and Ideal Medical Technologies, personal consulting fees from Dexcom, and has provided consulting services for Insulet (services paid to his institution). The authors declare no competing financial interests. Ethics approval and consent to participate: We were exempt from ethical approval by the Emory University Institutional Review Board for the analysis of secondary data. All data in Epic Cosmos are HIPAA compliant and expert determined de-identified.

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