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

Eli Lilly on Thursday said its next-generation obesity drug retatrutide cleared its first late-stage trial on Type 2 diabetes patients, helping them manage their blood sugar levels and lose weight. 

The drug lowered hemoglobin A1c — a key measure of blood sugar levels — by an average of 1.7% to 2% across different doses at 40 weeks compared to placebo, meeting the study's main goal. Patients started 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 at the highest dose lose an average of 16.8% of their weight, or 36.6 pounds, at 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 weight.

Patients with Type 2 diabetes historically struggle to lose weight, so Lilly is "very excited" to see that the drug led to both 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 discontinuation rates due to side effects, which were up to 5%, he added.

They are the second late-stage results to date on retatrutide, which works differently from 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 blockbuster weight loss injection Zepbound and its upcoming pill, orforglipron. 

But Lilly has yet to file for approval for the drug 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 greatest Lilly has seen within its portfolio: The highest dose of Zepbound lowered the measure by more than 2% at 40 weeks in two separate trials on diabetes patients.

But Custer said retatrutide's A1C reduction is still "very, very strong" compared to other diabetes medications that don't target gut hormones. 

He also said that having options in the obesity and diabetes space will be important because "not everybody is going to be helped with or satisfied with the same treatment." Choosing which drug to take will depend on "individualized tailoring of solutions and patients," particularly earlier in their diabetes treatment, he added. 

For example, Custer said patients who want to regulate their blood sugar could benefit from either Zepbound or retatrutide. But if they are 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 did. In one 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 the 40-week mark.

Retatrutide's safety profile was similar to other injectable diabetes and obesity drugs, primarily causing gastrointestinal side effects. Around 26.5% of patients on the highest dose experienced nausea, while roughly 22.8% and 17.6% had diarrhea and vomiting, respectively. 

Low rates of patients experienced dysesthesia, which is an unpleasant nerve sensation.

Dubbed the "triple G" drug, retatrutide works by mimicking three hunger-regulating hormones – GLP-1, GIP and glucagon – rather than just one or two like existing treatments. That appears to have more potent 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, mimics only GLP-1.

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

Novo's newly acquired drug is a clear potential competitor to retatrutide because it similarly uses a three-pronged approach to promoting weight loss and regulating blood sugar. But Novo's treatment is much earlier in development, meaning it will take several years before it reaches patients.