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

Jithin Sam Varghese; David R Goldsmith; Robert O Cotes; Vishnu Ravikumar; Mohammed K Ali; Francisco J Pasquel

doi:10.1038/s41366-025-01885-4

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

Int J Obes (Lond). 2025 Aug 15. doi: 10.1038/s41366-025-01885-4. Online ahead of print.

Authors

Jithin Sam Varghese^{1

2}, David R Goldsmith³, Robert O Cotes³, Vishnu Ravikumar⁴, Mohammed K Ali^{5

6

7}, Francisco J Pasquel^{5

6

8}

Affiliations

¹ Emory Global Diabetes Research Center of Woodruff Health Sciences Center and Emory University, Atlanta, GA, USA. jvargh7@emory.edu.
² Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. jvargh7@emory.edu.
³ Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA, USA.
⁴ Office of Information Technology, Emory University, Atlanta, GA, USA.
⁵ Emory Global Diabetes Research Center of Woodruff Health Sciences Center and Emory University, Atlanta, GA, USA.
⁶ Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
⁷ Department of Preventive & Family Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
⁸ Division of Endocrinology, School of Medicine, Emory University, Atlanta, GA, USA.

PMID: 40817129
DOI: 10.1038/s41366-025-01885-4

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.