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Semaglutide and liraglutide are associated with the greatest weight reductions in patients with schizophreniaNew data shows weight loss options for people with schizophrenia

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Key Takeaway
Consider semaglutide or liraglutide for weight reduction in schizophrenia as they showed the greatest weight reductions.

This network meta-analysis evaluated the efficacy of various pharmacological interventions for weight reduction in patients with schizophrenia spectrum disorders (SSDs) treated with antipsychotics. The analysis included a total sample size of 5898.

Semaglutide was associated with a mean body weight reduction of -10.98 kg (95% CI, -13.33 to -8.62). Liraglutide showed a reduction of -5.43 kg (95% CI, -8.54 to -2.33). Other agents showed smaller reductions: topiramate (-3.95 kg; 95% CI, -5.89 to -2.02), metformin (-3.86 kg; 95% CI, -5.02 to -2.70), and exenatide (-2.97 kg; 95% CI, -5.83 to -0.11).

Semaglutide, liraglutide, topiramate, metformin, and exenatide were supported by moderate certainty of evidence. In contrast, ramelteon, nizatidine, and aripiprazole were associated with very low certainty of evidence. No major concerns were reported regarding gastrointestinal adverse effects or study discontinuation rates.

Clinical application is limited by the low certainty of evidence for several agents. Semaglutide, liraglutide, topiramate, metformin, and exenatide are associated with the greatest reductions in body weight among the options reviewed.

How this fits prior evidence

This finding addresses a gap in managing metabolic complications in schizophrenia. It builds upon the finding that AGE levels are significantly elevated in schizophrenia-spectrum disorders. While the current study focuses on weight reduction, it provides specific evidence for semaglutide and liraglutide as potent agents for weight management in this population.

Managing weight is a significant challenge for people living with schizophrenia. Many of these individuals take antipsychotic medications, which can often lead to weight gain as a side effect. Finding effective ways to manage weight while maintaining mental health is a major priority for patients and doctors alike.

A review of data from nearly 6,000 patients found that several medications could help reduce body weight. Semaglutide showed the largest reduction, followed by liraglutide, topiramate, metformin, and exenatide. These five medications were backed by the highest level of evidence in the study, making them stand out as effective options for weight management.

While the results are promising, the evidence for some other medications, like ramelteon and nizatidine, was much weaker. The study also noted that while some medications had gastrointestinal side effects, there were no major concerns regarding patients dropping out of the study. Talk to your doctor to see if these options fit your specific health needs.

What this means for you:
Semaglutide and four other medications show the most reliable results for weight reduction in schizophrenia patients.

Common questions

Which medications were most effective for weight loss?

The study found that semaglutide, liraglutide, topiramate, metformin, and exenatide were associated with the greatest reductions in body weight. These five medications were supported by the highest certainty of evidence compared to other options.

Are these weight loss medications safe for people with schizophrenia?

The study reported no major concerns regarding gastrointestinal side effects or patients dropping out of the study. However, you should always talk to your doctor to determine which treatment is safest and best for your specific health situation.

How much weight loss did patients see with semaglutide?

Patients using semaglutide saw an average weight reduction of 10.98 kg. This was the largest reduction found among the medications studied. You should consult your healthcare provider to discuss how this specific medication might work for you.

Study Details

Study typeSystematic review
EvidenceLevel 1
PublishedSep 2026
View Original Abstract ↓
IMPORTANCE: Significant weight gain is a concerning adverse effect of antipsychotic medications experienced by patients with schizophrenia spectrum disorders (SSDs). Its high prevalence and significant contribution to cardiometabolic morbidity in this population warrant better consensus on the management of antipsychotic-induced weight gain and related comorbidity. OBJECTIVES: To evaluate the association between pharmacological interventions and changes in body weight among antipsychotic-treated patients with SSDs. DATA SOURCES: Ovid MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) Search Portal were searched up to December 5, 2025. STUDY SELECTION: Randomized clinical trials examining any pharmacological intervention for weight reduction in antipsychotic-treated patients with SSDs were included. No restrictions to study duration were applied. DATA EXTRACTION AND SYNTHESIS: A systematic review and frequentist random-effects network meta-analysis was conducted. Certainty in the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) tool. The first round of data analysis took place between May 2025 to November 2025 and was updated in December 2025. MAIN OUTCOMES AND MEASURES: The primary outcome was change in body weight following treatment with pharmacological agent vs placebo or standard care. Secondary outcomes included other anthropometric and metabolic parameters. RESULTS: A total of 95 studies examining 39 individual pharmacological interventions were included in this review (pooled N = 5898). The network meta-analysis found that semaglutide (mean difference [MD], -10.98 kg; 95% CI, -13.33 to -8.62; k = 3; moderate certainty), liraglutide (MD, -5.43 kg; 95% CI, -8.54 to -2.33; k = 2; moderate certainty), topiramate (MD, -3.95 kg; 95% CI, -5.89 to -2.02; k = 5; moderate certainty), metformin (MD, -3.86 kg; 95% CI, -5.02 to -2.70; k = 16; moderate certainty), and exenatide (MD, -2.97 kg; 95% CI, -5.83 to -0.11; k = 3; moderate certainty) were associated with the most significant reductions in body weight compared to placebo. Other interventions including ramelteon, nizatidine, and aripiprazole were also found to be associated with weight-reducing effects but with very low certainty of evidence. Clinically meaningful weight change of 5% or greater was observed with semaglutide and metformin. Beneficial effects on other metabolic outcomes were also noted with several of the medications, and there were no major concerns with gastrointestinal adverse effects or leaving the study early (ie, dropouts) between interventions. CONCLUSIONS AND RELEVANCE: This systematic review and network meta-analysis found substantial variability in weight-related outcomes across pharmacological interventions for antipsychotic-treated individuals with SSDs. Semaglutide, liraglutide, topiramate, metformin, and exenatide were associated with the greatest reductions in body weight and were supported by the highest-certainty evidence, providing guidance for clinicians managing antipsychotic-associated weight gain.
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