Design: Updated systematic review of randomised trials (no pooled meta-analysis)
Population: 38 trials, 25,816 adults with overweight or obesity without diabetes
Primary outcome: Placebo-subtracted percentage weight loss and adverse events
Effect: Semaglutide SC -14.8% (-16.2 to -13.4); tirzepatide -19.0% (-21.6 to -16.4)

This updated systematic review included 38 randomised trials of at least 16 weeks, with 25,816 adults with overweight or obesity but no diabetes. Fourteen trials were new since the previous version.

Placebo-subtracted weight loss reached up to about 6% with liraglutide, 15% with subcutaneous semaglutide, 14% with oral semaglutide, 12% with orforglipron and 19% with tirzepatide. Investigational multi-agonists reached 22% to 24%. Gastrointestinal adverse events affected 76% on active drug and 40% on placebo; 10.7% and 3.4% stopped because of adverse events. Serious adverse events were 6.5% and 5.2%.

The trials differed too much for a single pooled estimate, and safety reporting was patchy. Head-to-head trials supported the ranking: tirzepatide above semaglutide, and semaglutide above liraglutide.

Set expectations by drug: trials reported placebo-subtracted loss of up to about 6% with liraglutide, 15% with semaglutide and 19% with tirzepatide.
Warn patients that nausea and other gastrointestinal effects are common, and titrate slowly.
Expect about one in ten to stop because of side effects.
Plan for long-term treatment; the trials measured weight loss while on the drug.

Why it matters

Patients now arrive asking about specific agents, and these figures let the choice be discussed in numbers.

The statistics, in plain English

Placebo-subtracted means the extra weight lost beyond what the placebo group lost. The figures come from separate trials with different populations and durations, so comparing them side by side is less reliable than a head-to-head trial.