Is retatrutide more effective than Ozempic?

Retatrutide 12 mg showed the greatest weight loss of all agents compared in a network meta-analysis of 27 randomised studies: on average 22.1% less body weight and 17.0 cm less waist circumference relative to placebo. In the phase 2 study published in the NEJM, the mean weight reduction after 48 weeks was as high as 24.2%, compared with 2.1% in the placebo group. Retatrutide 8 mg followed closely with 22.8% weight loss in that same phase 2 study.

Semaglutide 2.4 mg (the active ingredient in Ozempic and Wegovy) ranked lower than both doses of retatrutide and lower than tirzepatide in that same network meta-analysis. However, an important caveat applies: this is an indirect comparison. No direct head-to-head studies have been conducted in which retatrutide and semaglutide were tested alongside each other in the same trial. Such indirect comparisons are less certain than direct trials.

In people with type 2 diabetes the picture shifts somewhat. Tirzepatide performed better at lowering blood sugar (HbA1c and fasting glucose), while retatrutide again produced the greatest weight loss. People without diabetes generally lost more weight with retatrutide than people with diabetes.

In terms of side effects, gastrointestinal complaints such as nausea were the most frequently reported. They are dose-dependent and predominantly mild to moderate. A temporary increase in heart rate was also observed, which diminished after 24 weeks. Serious adverse events or low blood sugar were not seen more often.

Retatrutide has not yet been approved. The large phase 3 studies (the so-called TRIUMPH programme, with more than 5,800 planned participants) have not yet been completed. Until those results are available, the evidence for long-term efficacy and safety remains limited to phase 2 data.