The Eli Lilly logo appears at the company's office in San Diego, California, USA, on November 21, 2025.
Mike Blake | Reuters
Eli Lilly on Thursday said its next-generation anti-obesity drug, retatrutide, has passed its first late-stage trial in patients with type 2 diabetes, helping them control their blood sugar levels and lose weight.
The drug reduced hemoglobin A1c, a key measure of blood sugar levels, by an average of 1.7% to 2% at different doses at 40 weeks compared to placebo, meeting the primary endpoint of the study. Patients began the trial with an A1c in the range of 7% to 9.5% and were not taking other diabetes medications.
Retatrutide also met the study's second goal: helping patients who received the highest dose lose an average of 16.8% of their weight, or 36.6 pounds, at 40 weeks, when only patients who continued the drug were evaluated. When analyzing all participants, including those who stopped treatment, the highest dose of the drug helped patients lose 15.3% of their weight.
Patients with type 2 diabetes historically struggle to lose weight, so Lilly is “very excited” to see that the drug caused a competitive drop in blood sugar levels and significant weight loss, Ken Custer, president of Lilly Cardiometabolic Health, said in an interview.
The company was also “very pleased” with the relatively low treatment discontinuation rates due to side effects, which were as high as 5%, he added.
They are the second late-stage results to date on retatrutide, which works differently than existing injections and appears to be more effective, at least for weight loss. Lilly is betting big on retatrutide as the next pillar of its obesity portfolio after its successful weight-loss shot Zepbound and its upcoming pill, orforglipron.
But Lilly has yet to apply for approval of the obesity or diabetes drug. The company expects to report results from seven additional phase three trials of the drug before the end of the year.
There are no comparative trials of retatrutide with other drugs, making it difficult to directly compare efficacy.
Still, retatrutide's A1C reduction does not appear to be the largest Lilly has seen in its portfolio: Zepbound's highest dose reduced the measure by more than 2% at 40 weeks in two separate trials in patients with diabetes.
But Custer said retatrutide's A1C reduction is still “very, very strong” compared to other diabetes drugs that don't target gut hormones.
He also said it will be important to have options in the area of obesity and diabetes because “not everyone will get help or be satisfied with the same treatment.” Choosing which medication to take will depend on “individualized tailoring of solutions and patients,” particularly in the earlier stages of diabetes treatment, he added.
For example, Custer said patients who want to regulate their blood sugar could benefit from Zepbound or retatrutide. But if they're looking to lose more weight, the latter might be a better option, he said.
In the two separate diabetes trials, Zepbound helped patients lose slightly less weight than retatrutide. In a study called SURPASS-2, the highest dose of Zepbound helped patients lose an average of 13.1% of their weight at 40 weeks. In the other study, SURPASS-1, the highest dose helped patients lose an average of 11% of their weight at 40 weeks.
The safety profile of retatrutide was similar to that of other injectable medications for diabetes and obesity, causing primarily gastrointestinal side effects. About 26.5% of patients receiving the highest dose experienced nausea, while approximately 22.8% and 17.6% had diarrhea and vomiting, respectively.
A low percentage of patients experienced dysesthesia, which is an unpleasant nervous sensation.
Dubbed the “triple G” drug, retatrutide works by mimicking three hormones that regulate hunger (GLP-1, GIP and glucagon) instead of just one or two like existing treatments. It appears to have more powerful effects on a person's appetite and satisfaction with food than other treatments.
Tirzepatide, the active ingredient in Zepbound, mimics GLP-1 and GIP. Novo Nordisk's semaglutide, the active ingredient in Wegovy, uniquely mimics GLP-1.
As retatrutide approaches the market, Novo races 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 a clear potential competitor to retatrutide because it similarly uses a three-pronged approach to promote weight loss and regulate blood sugar. But the de Novo treatment is in a much earlier phase of development, meaning it will be several years before it reaches patients.
