Retatrutide Shows Strong Glycemic Control and Weight Loss in Phase 3 Trial

Retatrutide demonstrated promising results in its first late-stage trial for Type 2 Diabetes, reducing HbA1c levels by up to 2% and achieving an average weight loss of 16.8% over 40 weeks. The drug works by mimicking three key hunger-regulating hormones, and results from seven additional Phase 3 trials are anticipated later this year.

For the primary endpoint, participants taking retatrutide achieved average A1C reductions of up to 2.0%, using the efficacy estimand. For a key secondary endpoint, participants taking retatrutide lost up to an average of 36.6 lbs (16.8%), using the efficacy estimand. Weight loss continued through the end of the treatment period.

"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

Retatrutide also showed clinically meaningful improvements from baseline across key cardiovascular risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure.

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 (4 mg, 9 mg, 12 mg) were nausea (16.4%, 19.5%, 26.5%, respectively vs. 3.7% with placebo), diarrhea (18.7%, 26.3%, 22.8%, respectively vs. 4.5% with placebo) and vomiting (15.7%, 15.0%, 17.6%, respectively vs. 2.2% with placebo), and occurred primarily during dose escalation. Incidence of dysesthesia occurred in 4.5%, 2.3% and 4.4% (4 mg, 9 mg and 12 mg, respectively) of patients treated with retatrutide, compared to 0.0% with placebo. These dysesthesia events were generally mild, with a majority resolving during treatment. Discontinuation rates due to adverse events were 2.2%, 4.5% and 5.1% with retatrutide 4 mg, 9 mg and 12 mg, respectively, 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. Additional results from the retatrutide clinical trial program are expected over the next year.

About retatrutide

Retatrutide is an investigational once-weekly triple hormone receptor agonist. Retatrutide is a single molecule that activates the body's receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon. Lilly is studying retatrutide in several Phase 3 clinical trials to evaluate its potential efficacy and safety in obesity and overweight with at least one weight-related medical problem, type 2 diabetes, knee osteoarthritis, moderate-to-severe obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease. Retatrutide is an investigational molecule that is legally available only to participants in Lilly's clinical trials.

About TRANSCEND-T2D-1 and the TRANSCEND-T2D clinical trial program

TRANSCEND-T2D-1 (NCT06354660) is a Phase 3, 40-week, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of retatrutide with placebo in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone. The study randomized 537 participants in a 1:1:1:1 ratio to receive either retatrutide 4 mg, 9 mg or 12 mg, or placebo. The objective of the study was to demonstrate that retatrutide (4 mg, 9 mg or 12 mg) is superior to placebo in A1C reduction from baseline after 40 weeks, in adults with type 2 diabetes who have not taken any anti-diabetes medications for at least 90 days prior to visit one, and are naïve to insulin therapy except for gestational diabetes. Study participants had A1C between ≥7.0% and ≤9.5% and a BMI of ≥23 kg/m2 at visit one. Participants randomized to retatrutide initiated treatment with 2 mg once-weekly and increased the dose in a step-wise approach every four weeks until reaching the target dose of 4 mg (via one step at 2 mg), 9 mg (via steps at 2 mg, 4 mg and 6 mg) or 12 mg (via steps at 2 mg, 4 mg, 6 mg and 9 mg).

The TRANSCEND-T2D Phase 3 clinical trial program is evaluating the safety and efficacy of retatrutide for the treatment of adults with type 2 diabetes across three global registrational trials. The program, which began in 2024, has enrolled more than 2,050 participants and additional results are anticipated over the next year.