People with severe mental illness often gain weight because of the medicines they take, and the usual weight‑loss drugs only help a little. This review points out that a new peptide called cagrilintide (often combined with semaglutide) looks promising for cutting weight in this group, based on studies in the general population.

Psychotropic medications, especially antipsychotics, have been consistently shown to cause weight gain in individuals with severe mental illness (SMI), a population inherently challenged by poor physical health. Consequently, compared to the general population, this contributes to an increased cardiometabolic burden, including the risk of type 2 diabetes, dyslipidemia, and hypertension. Furthermore, comorbid obesity leads to treatment nonadherence, decreased quality of life, and increased risk of relapse, posing a challenge in the management of mental health. To address this, emerging agents investigated in the general population with potential to mitigate weight gain were explored to assess translatability to the SMI population. A literature search was conducted including agents approved for the management of obesity in the general population, along with upcoming agents under investigation in phase III trials with weight loss properties. Metformin and topiramate along with lifestyle interventions are commonly prescribed for weight gain in individuals with SMI; however, their weight loss potential is modest at best. This review identified tirzepatide and cagrilintide-semaglutide among others as promising agents for adjunctive pharmacological management of weight gain.