Lilly's retatrutide lowered A1C and weight in first phase 3 diabetes trial

Eli Lilly reported on March 19, 2026 that retatrutide, its investigational once-weekly injection, lowered blood sugar and body weight in adults with type 2 diabetes in a 40-week phase 3 trial called TRANSCEND-T2D-1 ^[1]. The trial met its main goal and all key secondary goals compared with placebo ^[1].

The study randomized 537 adults with type 2 diabetes who were not controlling their blood sugar through diet and exercise alone ^[1]. Their average A1C at the start was 7.9%, and their average body weight was 213.6 pounds, with a body mass index of 35.8 ^[1]. Participants had been diagnosed with diabetes for an average of 2.5 years and had not taken diabetes medication for at least 90 days before entering the study ^[1]. They were assigned to retatrutide 4 mg, 9 mg, 12 mg, or placebo, starting at 2 mg and stepping up every four weeks ^[1].

On A1C, retatrutide lowered the measure by an average of 1.7% to 2.0% at 40 weeks, compared with 0.8% for placebo, using the efficacy estimand, a calculation that assumes everyone stayed on treatment ^[1]. Under the treatment-regimen estimand, which counts people regardless of whether they stayed on the drug or started other diabetes medicines, reductions ranged from 1.7% to 1.9% versus 0.8% for placebo ^[1].

For weight, the 12 mg dose produced an average loss of 16.8% (36.6 pounds) using the efficacy estimand, compared with 2.5% (6.2 pounds) for placebo ^[1]. The 9 mg dose produced 15.5% and the 4 mg dose 11.5% ^[1]. Counting everyone regardless of adherence, losses were 15.3%, 13.9% and 11.5% across the three doses, versus 2.6% for placebo ^[1]. Lilly said weight loss had not plateaued by the end of the 40 weeks ^[1].

Side effects were common and generally rose with dose. In the 12 mg group, 26.5% of participants reported nausea, 22.8% reported diarrhea and 17.6% reported vomiting, compared with 3.7%, 4.5% and 2.2% on placebo; Lilly said these occurred mainly during dose escalation ^[1]. Rates of a sensation-related side effect called dysesthesia were 4.5%, 2.3% and 4.4% across the 4 mg, 9 mg and 12 mg groups, versus none on placebo. Lilly said these were generally mild and most resolved during treatment ^[1]. Discontinuations due to side effects were 2.2%, 4.5% and 5.1% across the doses, compared with none on placebo ^[1]. J.P. Morgan analysts noted that side-effect rates were higher than those seen with Lilly's tirzepatide, sold as Mounjaro for diabetes and Zepbound for weight loss, in a similar trial, partly offsetting the efficacy ^[2].

Analysts put the results next to other drugs. In separate 40-week late-stage trials, Lilly's experimental orforglipron pill produced an average weight loss of 7.9%, while tirzepatide produced 13.1% ^[2]. In an earlier trial in knee osteoarthritis, retatrutide produced an average 28.7% weight loss, more than Zepbound ^[2]. Scotiabank analyst Louise Chen said retatrutide "delivers the highest levels of weight loss we've seen from an obesity drug to date," calling it impressive in a group that tends to lose less weight than the general population ^[2]. RBC Capital Markets analysts expect a 2027 launch and about $4.9 billion in annual sales by 2030 ^[2].

Lilly said retatrutide also improved non-HDL cholesterol, triglycerides and systolic blood pressure, though the 4 mg dose was not included in the statistical control for those measures ^[1]. The topline announcement did not report how many participants reached an A1C in the normal range, and it did not include heart or kidney outcome data for this population.

Why it matters for patients

Retatrutide is not approved for any use. Lilly says it is legally available only to people enrolled in its clinical trials ^[1]. For adults with type 2 diabetes, the results suggest a possible future option that addresses blood sugar and weight at the same time, a combination that Lilly's Kenneth Custer said is often a struggle because obesity has historically been harder to treat in people with type 2 diabetes ^[1]. People with diabetes tend to lose less weight on this class of drugs than people without it, which is why analysts highlighted the weight numbers ^[2].

The trade-off is tolerability. Nausea, diarrhea and vomiting were more common than with placebo, and about 1 in 20 participants on the highest dose stopped treatment because of side effects ^[1]. How those rates compare with currently available drugs is a question analysts raised immediately, and the full data will not be public until they are presented and peer-reviewed ^[1][2].

What happens next

Detailed TRANSCEND-T2D-1 results are scheduled for presentation at the American Diabetes Association Scientific Sessions in June 2026 and for publication in a peer-reviewed journal ^[1]. More results from the retatrutide program are expected over the next year ^[1]. The TRANSCEND-T2D program includes three global registrational trials that began in 2024 and have enrolled more than 2,050 participants ^[1]. Retatrutide is also being studied in obesity and overweight with a weight-related condition, knee osteoarthritis, moderate-to-severe obstructive sleep apnea, chronic low back pain, cardiovascular and kidney outcomes, and metabolic dysfunction-associated steatotic liver disease ^[1]. RBC analysts anticipate a 2027 launch ^[2].