Lilly’s Retatrutide Shows Promise in Type 2 Diabetes Trial, Delivering Significant Weight Loss
Eli Lilly and Company announced positive topline results from the TRANSCEND-T2D-1 Phase 3 clinical trial evaluating retatrutide, an investigational GIP, GLP-1 and glucagon triple hormone receptor agonist, as an adjunct to diet and exercise for adults with type 2 diabetes. The trial demonstrated significant reductions in HbA1c and substantial weight loss.
Key Findings from the TRANSCEND-T2D-1 Trial
The study, conducted with adults diagnosed with type 2 diabetes and inadequate glycemic control with diet and exercise alone, revealed that retatrutide met both its primary and key secondary endpoints. Participants in the trial had a indicate duration of diabetes of 2.5 years.
- HbA1c Reduction: Retatrutide lowered A1C by an average of 1.7% to 2.0% across different doses at 40 weeks compared to placebo.1
- Weight Loss: Participants taking the 12 mg dose of retatrutide lost an average of 36.6 lbs (16.8%) at 40 weeks.1
- Continued Weight Loss: Notably, no weight loss plateau was observed, with participants continuing to lose weight throughout the 40-week treatment period.1
How Retatrutide Works
Retatrutide is a “triple G” drug, meaning it mimics the effects of three hunger-regulating hormones: GLP-1, GIP, and glucagon. This differs from existing treatments like tirzepatide (Zepbound), which mimics GLP-1 and GIP, and semaglutide (Wegovy), which mimics only GLP-1.2 This multi-pronged approach appears to have a more potent effect on appetite and food satisfaction.
Lilly’s Expanding Obesity Portfolio
Lilly is positioning retatrutide as a key component of its growing cardiometabolic health portfolio, alongside Zepbound and the upcoming oral drug, orforglipron.1 Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health, emphasized the potential of retatrutide to address the challenges many individuals with type 2 diabetes face in achieving both A1C control and weight loss.1
Safety and Discontinuation Rates
The trial reported relatively low discontinuation rates due to side effects, with rates up to 5%.1 The most common side effects were gastrointestinal, including nausea (26.5% at the highest dose), diarrhea (roughly 22.8%), and vomiting (roughly 17.6%). A small percentage of patients experienced dysesthesia, an unpleasant nerve sensation.1
Looking Ahead
While these results are promising, Lilly has not yet filed for regulatory approval for retatrutide for either obesity or diabetes. The company anticipates reporting data from seven additional Phase 3 trials by the end of 2026.1 Currently, there are no head-to-head trials comparing retatrutide directly to other drugs in its class.
Comparison to Zepbound
While retatrutide’s A1C reduction is strong, Zepbound’s highest dose lowered A1C by more than 2% in separate trials on diabetes patients.1 However, Custer noted that retatrutide’s A1C reduction remains “very, very strong” compared to other diabetes medications that do not target gut hormones.1 Zepbound helped patients lose an average of 13.1% to 11% of their weight in separate trials, slightly less than the 16.8% weight loss observed with the highest dose of retatrutide.1
Competition from Novo Nordisk
Novo Nordisk is also actively developing a triple-hormone agonist to compete with retatrutide, having agreed to acquire rights to an early-stage drug from United Laboratories International in March 2025.1 However, Novo’s treatment is in earlier stages of development and will capture several years to reach patients.
1 Lilly’s Triple Agonist, Retatrutide, Demonstrated Significant Reductions in A1C and Weight in First Phase 3 Trial for Treatment of Type 2 Diabetes, PR Newswire, March 19, 2026.
2 Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a phase 2 trial, PubMed, 2023.