A new meta-analysis finds semaglutide is the most effective weight-loss drug for patients with schizophrenia spectrum disorder taking antipsychotics. Analyzing 95 clinical trials and 39 medications, researchers found semaglutide was linked to nearly 11 kg of weight loss — far outpacing the next best options like liraglutide and metformin. The findings, published in JAMA Psychiatry, offer clearer guidance for clinicians managing a common and serious side effect of antipsychotic therapy.
Weight gain is one of the most common — and most frustrating — side effects of antipsychotic medications, and it's a leading reason patients stop taking them. Now, a large systematic review and network meta-analysis published in JAMA Psychiatry offers some much-needed clarity on which weight-loss drugs actually work best for this population.
Researchers analyzed 95 randomized clinical trials covering 39 pharmacologic interventions in adults with schizophrenia spectrum disorder (SSD). The standout winner? Semaglutide, the GLP-1 receptor agonist, which was associated with nearly 11 kg (about 24 lbs) of weight loss — more than double the next best options. Liraglutide, topiramate, metformin, and exenatide also showed meaningful results, though with significantly smaller effects.
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Why it matters: Antipsychotic-associated weight gain carries serious cardiometabolic risks and undermines treatment adherence in patients with schizophrenia. These findings give clinicians a clearer, evidence-based roadmap for intervening early — with semaglutide emerging as the frontrunner, especially for long-term management.
