Excess weight during antipsychotic treatment: GLP-1 agonists appear effective, but psychiatric safety remains uncertain

Eight trials in a directly relevant population

Managing excess weight associated with antipsychotics cannot simply rely on results obtained in the general population. This systematic review specifically focuses on adults receiving antipsychotic treatment who have associated excess weight or metabolic disturbances.

The researchers brought together eight randomized trials totaling 535 participants. Their literature search covered studies up to September 13, 2026. The results presented here come solely from the PubMed abstract: the full text was not consulted. The abstract does not detail the comparators or the duration of each trial, which limits practical interpretation.

Weight reduction, but not an individual prediction

The mean difference in weight change was −6.54 kg compared with the comparator groups, with a 95% confidence interval from −9.80 to −3.29 kg. However, heterogeneity was very high, with an I² of 92%: the trials produced substantially different results. This average therefore cannot predict how much weight any individual would lose.

The review also reports a reduction in waist circumference of 5.22 cm and in HbA1c, an indicator of blood glucose over time, of 0.32 percentage points. However, no statistically significant effect was found on total cholesterol, triglycerides, or HDL cholesterol.

These findings concern weight and metabolic markers. On their own, they do not demonstrate a reduction in cardiovascular complications or an improvement in long-term health.

Gastrointestinal side effects increase, while psychiatric safety remains an open question

GLP-1 agonists increase the risks of nausea, vomiting, and constipation in this review. The abstract does not provide the corresponding absolute frequencies, so it is impossible to specify how many additional participants experienced these effects.

No statistically significant increase in serious adverse events or treatment discontinuations was detected. This does not demonstrate an absence of risk, particularly for rare events.

Crucially, psychiatric adverse events were too few to pool. The authors conclude that psychiatric safety cannot be established and call for longer trials with standardized collection of adverse-event data.

What we can take away

This review supports a benefit for weight and blood glucose in adults taking antipsychotics. It is not sufficient to establish psychiatric safety or long-term benefit, and it does not justify changing your treatment on your own.