Retatrutide demonstrated reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes

Posted on March 24, 2026

Eli Lilly has recently announced positive topline results from TRANSCEND-T2D-1, a Phase 3 clinical trial evaluating the efficacy and safety of retatrutide, an investigational first-in-class GIP, GLP-1 and glucagon triple hormone receptor agonist, as an adjunct to diet and exercise. The trial enrolled adults diagnosed with type 2 diabetes with inadequate glycemic control with diet and exercise alone, and a mean duration of diabetes of 2.5 years. Retatrutide met the primary and all key secondary endpoints, delivering superior A1C reduction and weight loss at 40 weeks compared to placebo, using both the efficacy and treatment-regimen estimands.

“For many people with type 2 diabetes, it is a struggle to achieve both A1C control and weight loss, since obesity has historically been harder to treat for those with type 2 diabetes,” said Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health. “With triple agonist retatrutide, we set out to make a molecule that could help patients achieve substantial A1C reduction and weight loss. These results support the remarkable potential of this novel molecule for people living with type 2 diabetes, with up to 2% A1C improvement and nearly 17% weight loss in 40 weeks of treatment.”

TRANSCEND-T2D-1 Efficacy Results

Primary Endpoint
Retatrutide 4 mg   Retatrutide 9 mg Retatrutide 12 mg Placebo
Change in A1C
from a baseline of
7.9% at 40 weeks

 

 Efficacy estimand

 

 -1.7 % -2.0 % -1.9 % -0.8 %
Treatment-
regimen estimand		 -1.7 % -1.9 % -1.9 % -0.8 %
Key Secondary Endpoint
Percentage
change in body
weight at 40
weeks from a
baseline of 96.9 kg
(213.6 lbs; BMI
of 35.8 kg/m2)		 Efficacy estimand -11.5%

 

(-11.1 kg;
-24.5 lbs)

 

 -15.5%

 

(-15.1 kg;
-33.3 lbs)

 -16.8%

 

(-16.6 kg;
-36.6 lbs)

 -2.5%

 

(-2.8 kg;
-6.2 lbs)
Treatment-
regimen estimand		 -11.5%

 

(-11.1 kg;
-24.5 lbs)

 

 -13.9%

 

(-13.5 kg;
-29.8 lbs)

  -15.3%

 

(-15.1 kg;
-33.3 lbs)

 -2.6%

 

(-2.7 kg;
-6.0 lbs)

Note that consistent with the types of adverse events seen in clinical trials for other incretin-based therapies, the most common adverse events among participants treated with retatrutide were nausea diarrhea and vomiting and occurred primarily during dose escalation. Incidence of dysesthesia occurred in 4.5%, 2.3% and 4.4% of patients treated with retatrutide, compared to 0.0% with placebo.

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

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