Five drugs stand out for antipsychotic-induced weight gain, study finds

Metformin, topiramate and three GLP-1 receptor agonists, semaglutide, liraglutide and exenatide, emerged as the five most effective pharmacologic options for managing antipsychotic-induced weight gain, according to Mahavir Agarwal, M.D., Ph.D., a psychiatrist and scientist in the Schizophrenia Division at the Centre for Addiction and Mental Health in Toronto and an associate professor in the Department of Psychiatry at the University of Toronto. Agarwal discussed the findings from a network meta-analysis of pharmacological interventions for antipsychotic-related weight gain published in JAMA Psychiatry.

In this interview with Managed Healthcare Executive, Agarwal walks through how metformin, topiramate and GLP-1 receptor agonists each fill a distinct role in managing antipsychotic-induced metabolic dysfunction and how cost and coverage differences among the three shape which option is realistic for a given patient.

Agarwal said metformin has the strongest evidence base of the group and the longest track record, making it well suited as a first-line option. It can be started alongside a patient's very first antipsychotic dose or introduced later, though it tends to work best when started early. He described the drug as meeting a rare combination of criteria: low cost, general tolerability, and effectiveness when used in the right circumstances.

GLP-1 receptor agonists become a strong option once weight gain is more established or when metformin alone is not enough, Agarwal said, pointing to semaglutide as an example. Access remains a barrier, however, since GLP-1 drugs are not covered by many public insurance plans. Agarwal noted that in Canada, where a generic version of semaglutide now costs about $100 a month, the drug still remains out of reach for many patients.

Topiramate, Agarwal said, is often more accessible to patients on public disability programs than GLP-1 therapies. Agarwal cited research showing that appropriately selected patients on topiramate lost about five kilograms on average, with roughly one in three patients achieving at least 5% body weight loss. He noted that topiramate's side effects require careful monitoring when the drug is introduced.