Eli Lilly’s obesity drug retatrutide clears late-stage diabetes trial

Eli Lilly It said on Thursday that its next-generation obesity drug retatretide has cleared its first late-stage trial in type 2 diabetes patients to help manage their blood sugar levels and help them lose weight.

The drug reduced hemoglobin A1c — a key measure of blood sugar levels — by an average of 1.7% to 2% over 40 weeks at different doses compared to placebo, meeting the study’s main goal. Patients began the trial with an A1c in the 7% to 9.5% range and were not taking other diabetes medications.

Retatrutide also met the study’s second goal, helping patients at the high dose lose an average of 16.8% of their weight, or 36.6 pounds, over 40 weeks, when evaluating only patients who stayed on the drug. When analyzing all participants, including those who discontinued treatment, the highest dose of the drug helped patients lose 15.3% of their body weight.

Patients with type 2 diabetes have historically struggled to lose weight, so Lilly was “very excited” to see that the drug led to a competitive drop in blood sugar levels and significant weight loss, Ken Custer, president of Lilly Cardiometabolic Health, said in an interview.

He said the company is “very happy” with relatively low discontinuation rates due to side effects of up to 5%.

Those are the second late-stage results to date on retatrutide, which works differently than existing injections and is at least more effective for weight loss. Lilly is betting big on retatrutide as the next pillar of its obesity portfolio after its blockbuster weight loss injection Zepbound and its upcoming pill, orforglipron.

But Lilly has yet to file for drug approval for obesity or diabetes. The company expects to report findings from seven additional phase three trials on the drug by the end of the year.

There are no head-to-head trials of retatrutide against other drugs, making it difficult to directly compare efficacy.

Still, retatrutide’s A1C reduction doesn’t appear to be the largest scale Lilly has seen in its portfolio: The highest dose of Zepbound reduced the measure by more than 2% over 40 weeks in two separate trials on diabetic patients.

But Custer said retatrutide’s A1C reduction was still “very, very strong” compared with other diabetes drugs that don’t target gut hormones.

He said having options in the obesity and diabetes space is important because “not everyone is going to be helped or satisfied with the same treatment.” Choosing which drug to take depends on “individual tailoring of solutions and patients,” especially in their diabetes treatment, he said.

For example, Custer said, patients who want to control their blood sugar may benefit from Zepbound or retatrutide. But if he wants to lose more weight, the latter is a better option, he said.

In two separate diabetes trials, Zepbound helped patients lose slightly less weight than did retatrutide. In a study called SURPASS-2, the highest dose of Zepbound helped patients lose an average of 13.1% weight over 40 weeks. In the other study, SURPASS-1, the high dose helped patients lose an average of 11% of their weight at the 40-week mark.

Retatrutide’s safety profile was similar to that of other injectable diabetes and obesity drugs, with primarily gastrointestinal side effects. Approximately 26.5% of patients who ingested high doses experienced nausea, while approximately 22.8% and 17.6% had diarrhea and vomiting, respectively.

A small proportion of patients experienced dysesthesia, an unpleasant nerve sensation.

Retatrutide, a so-called “triple G” drug, works by mimicking three appetite-regulating hormones — GLP-1, GIP and glucagon — like only one or two of the existing treatments. It appears to have stronger effects on a person’s appetite and food satisfaction than other treatments.

Tirgepatide, the active ingredient in Zepbound, mimics GLP-1 and GIP. Novo Nordisk’s semaglutide, the active ingredient in Vegovi, only mimics GLP-1.

As Retatrutide inches closer to market, Novo is racing to catch up with Lilly. In March 2025, Novo said it had agreed to pay up to $2 billion for the rights to an early experimental drug from Chinese pharmaceutical company United Laboratories International.

Novo’s newly acquired drug is an obvious potential competitor to retatrutide because it uses a three-pronged approach to promote weight loss and control blood sugar. But Novo’s treatment is very early in development, meaning it will be several years before it reaches patients.