Researchers testing Eli Lilly’s experimental Phase III trial of retatrutide found an average weight loss of 18.8% in adults with obesity or overweight and type 2 diabetes, along with improved blood sugar control.
Participants in the highest-dose group received 12 mg weekly for 80 weeks. Those receiving placebo lost an average of 5.1% of their starting weight.
TRIUMPH-2 enrolled 1,152 adults at 92 centres in eight countries. Eli Lilly and Company funded the randomised, double-blind study, which The Lancet published online on September 29.
Researchers included all randomised participants in the primary weight-loss analysis, regardless of whether they completed treatment, and used statistical methods to estimate missing measurements.
The recent analysis showed that participants who received lower doses lost less weight on average than those in the higher-dose groups. Specifically, participants who received 4 mg lost an average of 11.9% of their body weight. In comparison, those who received 9 mg lost an average of 16.8% of their body weight. However, Lilly’s previously reported figure of 20.8% came from a separate analysis that assumed all participants remained on treatment throughout the study.
Under that analysis, the company reported a 1.5-percentage-point reduction in glycated haemoglobin (HbA1c) for the highest-dose group. The starting average was 7.7%.
Gastrointestinal problems were the most frequently reported adverse effects. In the highest-dose group, 34% reported diarrhoea and 28% reported nausea. The corresponding placebo rates were 13% and 8%. Adverse events or death led to permanent treatment discontinuation in 8–12% of the higher-dose groups, compared with 5% receiving placebo.
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Seven participants died during the study, and Investigators judged all the deaths unrelated to the study treatment.
Retatrutide activates receptors for glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Researchers describe it as a triple receptor agonist.
The findings also showed improvements in blood pressure, triglycerides and high-sensitivity C-reactive protein (hsCRP), an inflammation marker.
Study co-author Dr Juan Pablo Frías, of the Los Angeles Institute for Metabolic Research, presented the results at the European Association for the Study of Diabetes annual meeting in Milan.
Retatrutide remains experimental. The US Food and Drug Administration (FDA) has not approved it. Lilly announced in July that it planned to seek US approval in the first quarter of 2027.
(With additional input from The Science Times)
