Retatrutide, an investigational triple hormone agonist, produced significant reductions in both A1c and weight in a phase 3 trial of people with type 2 diabetes (T2D), manufacturer Eli Lilly and Company reported.

The drug activates receptors for glucose-dependent insulinotropic polypeptide, GLP-1, and glucagon, combined into a single molecule. On March 19, 2026, Eli Lilly and Company released positive top-line results for Effect of Retatrutide Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone (TRANSCEND-T2D-1).

The 40-week trial randomly assigned 537 people with inadequately controlled T2D (A1c, 7.0%-9.5%) with diet and exercise alone to one of three retatrutide doses — 4 mg, 9 mg, or 12 mg — or placebo. For the primary endpoint, retatrutide resulted in A1c reductions of 1.7-2.0 percentage points for the efficacy estimand and 1.7-1.9 percentage points for the treatment regimen estimand vs just 0.8 percentage points with placebo in both analyses.

Body weight, a secondary endpoint, was reduced from a baseline of 96.9 kg by 11.5%-16.8% with retatrutide at 40 weeks vs just 2.5% with placebo for the efficacy estimand. The weight loss with the highest retatrutide dose corresponded to an average of 36.6 lb, with weight loss continuing through the end of the treatment period, Eli Lilly and Company said.

“Clinically meaningful” improvements with retatrutide were also seen in cardiovascular risk factors, including non-high-density lipoprotein cholesterol, triglycerides, and systolic blood pressure, the company reported.

Adverse events were consistent with those seen in trials of other incretin-based medications, including nausea (16.4%-26.5% vs 3.7% with placebo), diarrhea (18.7%-26.3% vs 4.5%), and vomiting (15.0%-17.6% vs 2.2%). These events occurred primarily during dose escalation. Dysesthesia occurred in 2.3%-4.5% with retatrutide vs none with placebo.

Discontinuation rates due to adverse events were 2.2%-5.1% vs none with placebo.

Detailed results of TRANSCEND-T2D-1 will be presented at the American Diabetes Association Scientific Sessions in June 2026 and published in a peer-reviewed journal.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X @MiriamETucker and BlueSky @miriametucker.bsky.social.