Phase 3 retatrutide trial reports lower A1C and body weight in type 2 diabetes

What happened

A phase 3 trial has reported results for retatrutide as a stand-alone treatment in adults with type 2 diabetes that was not adequately controlled through diet and exercise. Retatrutide is a once-weekly experimental medicine that activates GIP, GLP-1 and glucagon receptors. It is not approved by the FDA.

TRANSCEND-T2D-1 enrolled 537 adults at 48 sites in the United States, Mexico and India. Participants were randomly assigned to receive 4 mg, 9 mg or 12 mg of retatrutide, or placebo, for 40 weeks. Their average starting A1C was 7.9%, average BMI was 35.8 and average duration of diabetes was 2.5 years.

In the treatment-regimen analysis, average A1C declined by 1.69 percentage points with 4 mg, 1.86 points with 9 mg and 1.94 points with 12 mg. The placebo group had an average decline of 0.81 points. Average body-weight reductions were 11.5% on 4 mg, 13.9% on 9 mg and 15.3% on 12 mg. Placebo participants had a 2.6% average reduction.

Gastrointestinal problems were the most frequent adverse events and were usually described as mild or moderate. Between 2% and 5% of retatrutide participants stopped the study treatment because of an adverse event, compared with none in the placebo arm. No severe hypoglycemia was reported. Two participants died during the study, and investigators judged both deaths unrelated to the drug.

What it means

This is randomized phase 3 evidence that retatrutide can lower blood glucose and body weight when used alone in the specific population studied. All three tested doses produced larger average changes than placebo at week 40.

The results also provide a more complete safety picture than a top-line company announcement. The paper reports treatment completion, discontinuation and adverse-event information, and the trial registration makes the protocol easier to check.

What it does not mean

The trial was not an FDA approval, and retatrutide should not be bought as a compounded or research product. The study did not compare it with semaglutide, tirzepatide or another active diabetes medicine. It also does not show what happens after several years of treatment or whether the drug reduces cardiovascular events.

These findings should not be generalized to every person with type 2 diabetes. Participants entered without glucose-lowering medication and had A1C from 7.0% to 9.5%. Eli Lilly funded the study, and several authors were company employees or shareholders.