- Design
- Systematic review and meta-analysis of randomised trials
- Population
- 8 trials, 535 adults with antipsychotic-related weight gain or metabolic dysregulation
- Primary outcome
- Change in body weight, BMI, HbA1c and total cholesterol
- Effect
- Weight MD -6.54 kg (95% CI -9.80 to -3.29), I² 92%
A meta-analysis in the European Journal of Clinical Pharmacology pooled eight randomised trials (535 adults) testing GLP-1 receptor agonists in people with weight gain or metabolic problems on antipsychotics. Published on 24 October 2026.
Treatment was associated with an average weight loss of 6.5 kg more than control (95% CI 3.3 to 9.8 kg), a BMI fall of 2.3, HbA1c down 0.32 percentage points and waist circumference down 5.2 cm. Semaglutide outperformed liraglutide, and longer treatment gave more loss. Nausea, vomiting and constipation were more common; serious adverse events and dropouts were not. Psychiatric adverse events were too sparse to pool.
Antipsychotic weight gain is a large part of why people with severe mental illness die years earlier, and switching antipsychotic is often not an option. This gives physicians a reasonable add-on.
The trials were small and heterogeneous, and psychiatric safety remains unknown, so involve the psychiatrist and watch mental state closely when starting.
- Consider a GLP-1 receptor agonist for significant weight gain on an antipsychotic when switching is not possible
- Agree the plan with the treating psychiatrist and review mental state after starting
- Warn about nausea and constipation, which may add to constipation from clozapine
- Recheck HbA1c, lipids and weight at three months to judge response
- Keep metformin in mind as a cheaper first step, particularly with prediabetes
Why it matters
Metabolic harm from antipsychotics is now something physicians can treat directly rather than accept.
Don't overread it
Psychiatric safety could not be assessed from these trials.
The statistics, in plain English
The weight result is clearly beyond chance, but I² of 92% means the trials disagreed widely on how much weight was lost. The pooled 6.5 kg is an average across very different drugs, doses and durations.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for internal medicine, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free