GLP-1 receptor agonists like semaglutide and liraglutide show promise for treating weight gain caused by antipsychotics and other psychiatric drugs, with metformin being the most studied option currently.
Emerging promiseGLP-1 receptor agonists (semaglutide, liraglutide, exenatide) for treating psychotropic drug-related weight gain, pending large clinical trials
What the researchers found
Psychotropic drug-related weight gain (PDWG) is a major barrier to psychiatric treatment adherence. The review found:
- Differential weight gain liability exists across antipsychotics, antidepressants, and anticonvulsants, and newer agents with lower liability should be prioritized
- Lithium's weight gain effect is lower than previously thought
- Lifestyle modification is effective and comparable to general population results
- Metformin is the most-studied pharmacological treatment for both prevention and treatment of PDWG
- GLP-1 receptor agonists (liraglutide, exenatide, semaglutide) show promising emerging data
- Most other pharmacologic antidotes (topiramate, H2 antagonists) have only low-confidence evidence
- Future research priorities include large trials of GLP-1 RAs and tirzepatide in psychiatric populations
Why it matters
Psychiatric patients already face elevated obesity risk, and weight gain from medications compounds the problem while driving treatment non-adherence. GLP-1 receptor agonists could address a critical unmet need by allowing patients to maintain psychiatric treatment without the metabolic costs that currently force many to choose between mental health and physical health.
How the study worked
This is a narrative review published in The American Journal of Psychiatry, synthesizing evidence on the epidemiology, risk factors, prevention, and treatment of psychotropic drug-related weight gain across antipsychotics, antidepressants, anticonvulsants, and lithium.
What this study cannot tell us
This is a narrative review, not a systematic review with meta-analysis. The GLP-1 RA evidence for PDWG specifically is still early-stage, with most data coming from small studies. The review does not provide pooled effect sizes. Interactions between GLP-1 RAs and psychiatric medications have not been well studied.
How to read the evidence
This is an expert narrative review published in a top-tier psychiatry journal. While it provides a comprehensive overview, the evidence for GLP-1 RAs specifically in PDWG is described as emerging, with most pharmacologic antidotes supported by only low-confidence data.
When this study was published
Published in 2024 in The American Journal of Psychiatry, this is a current and authoritative review reflecting the latest evidence at the intersection of metabolic and psychiatric medicine.
The bigger picture
This review reflects a growing recognition that metabolic health and psychiatric health are deeply interconnected. The potential for GLP-1 receptor agonists to help psychiatric patients manage medication-related weight gain could expand the clinical role of these peptide drugs far beyond diabetes and obesity into mental health care.
Questions still open
- Could GLP-1 receptor agonists be prescribed alongside antipsychotics from the start to prevent weight gain rather than treating it after the fact?
- Are there safety concerns with combining GLP-1 RAs and psychiatric medications, particularly regarding nausea and appetite suppression?
- Would tirzepatide's dual mechanism provide even greater benefit for antipsychotic-related weight gain?
Common questions
Can semaglutide help with weight gain from antipsychotics?
What's the best current treatment for medication-related weight gain?
Read the original research
Psychotropic Drug-Related Weight Gain and Its Treatment.
The American journal of psychiatry, 181(1), 26-38
Citation
McIntyre, Roger S; Kwan, Angela T H; Rosenblat, Joshua D; Teopiz, Kayla M; Mansur, Rodrigo B. (2024). Psychotropic Drug-Related Weight Gain and Its Treatment.. The American journal of psychiatry, 181(1), 26-38. https://doi.org/10.1176/appi.ajp.20230922