Design: Updated systematic review of randomised trials (≥16 weeks)
Population: 38 trials, 25,816 adults with overweight or obesity without diabetes
Primary outcome: Placebo-subtracted percentage weight change
Effect: Up to −19.0% tirzepatide, −14.8% s.c. semaglutide, −5.8% liraglutide; GI AEs 76% vs 40%

This updated systematic review, published 1 September, added 14 trials to a previous version, giving 38 randomised trials of at least 16 weeks with 25,816 adults with overweight or obesity and no diabetes. Heterogeneity prevented a single pooled estimate, so results are reported per drug.

The best placebo-subtracted weight loss reported for each available drug was: liraglutide −5.8%, oral semaglutide −14.3%, subcutaneous semaglutide −14.8%, orforglipron −12.4% and tirzepatide −19.0%. Investigational multi-agonists went further, with retatrutide −22.1% and amycretin −23.9%. Head-to-head trials favoured semaglutide over liraglutide, and tirzepatide over semaglutide.

Gastrointestinal effects occurred in 76% against 40% on placebo, and 10.7% stopped for side effects against 3.4%. Serious adverse events were 6.5% against 5.2%. Safety reporting was inconsistent, and the trials were too short to judge long-term harms.

For the ward physician, these drugs now arrive with patients: in pre-operative assessment, in the patient admitted vomiting, and in the question of whether to restart them on discharge.

Record GLP-1-based drugs in the admission drug history; patients often do not list weekly injections.
In a patient on one of these drugs admitted with vomiting or poor intake, consider the drug as a cause and assess for dehydration and acute kidney injury.
Check the perioperative plan for these drugs before elective procedures, since slowed gastric emptying affects aspiration risk.
Liraglutide gives much smaller weight loss than semaglutide or tirzepatide; this matters when cost forces a choice.

Why it matters

Once-weekly injections for weight are now common enough to be a routine cause of inpatient symptoms and perioperative questions.

The statistics, in plain English

Placebo-subtracted means the extra weight lost beyond the placebo group. These are the largest values reported for each drug, often at the highest dose, so they describe what is possible rather than what an average patient will lose.