Eli Lilly’s obesity drug retaretide eliminates late-stage diabetes trial

Eli Lilly US pharmaceutical company Retatrotide said its next-generation obesity drug, Retatrotide, has cleared the first late-stage trial in patients with type 2 diabetes, helping them manage 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% across different doses over 40 weeks compared to placebo, meeting the study’s main goal. Patients started the trial with an A1c level between 7% and 9.5%, and were not taking other diabetes medications.

Retatrutide also met the study’s second goal, which was to help patients taking the highest dose lose an average of 16.8% of their weight, or 36.6 pounds, over 40 weeks, when evaluating only patients who continued taking the drug. 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 has led to competitively lower blood sugar levels and significant weight loss, Ken Custer, president of Lilly Cardiometabolic Health, said in an interview.

He added that the company was also “very pleased” with the relatively low discontinuation rates due to side effects, which reached 5%.

This is the second late-stage result so far of retaretide, which works differently than existing injections and appears to be more effective, at least for weight loss. Lilly is betting big on retatrotide as the next pillar of its obesity portfolio following its blockbuster weight-loss injection Zepbound and its upcoming pill Orforglipron.

But Lilly has not yet applied for approval for the drug to treat obesity or diabetes. The company expects to announce the results of seven additional phase III trials on the drug by the end of the year.

There are no head-to-head trials of retatrotide with other drugs, making it difficult to compare effectiveness directly.

However, retatrutide’s A1C reduction does not appear to be the greatest Lilly has seen within its portfolio: The highest dose of Zepbound lowered the measure by more than 2% over 40 weeks in two separate trials in patients with diabetes.

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

He also said having options in obesity and diabetes would be important because “not everyone will be helped or satisfied with the same treatment.” He added that choosing which medication to take will depend on “the individual design of solutions and patients,” especially early in diabetes treatment.

For example, patients who want to regulate their blood sugar could benefit from Zepbound or retatrutide, Custer said. But if they are looking to lose more weight, the latter may be the better option.

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

The safety profile of retaretide was similar to other injectable diabetes and obesity medications, primarily causing gastrointestinal side effects. About 26.5% of patients taking the highest dose experienced nausea, while about 22.8% and 17.6% had diarrhea and vomiting, respectively.

Low rates of patients experience dysesthesia, an unpleasant nerve sensation.

Retatrotide, called the “Triple G” drug, works by mimicking three hormones that regulate hunger — GLP-1, GIP, and glucagon — instead of just one or two like existing treatments. This appears to have stronger effects on a person’s appetite and food satisfaction than other treatments.

Tirzepatide, the active ingredient in Zepbound, mimics GLP-1 and GIP. Novo Nordisk semaglutide, the active ingredient in Wegovy, mimics only GLP-1.

As Retrotide approaches the 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 drugmaker United Laboratories International.

Novo’s newly acquired drug Novo is an obvious potential competitor to retaretide because it similarly uses a three-pronged approach to promote weight loss and blood sugar regulation. But Novo’s treatment is still in the early stage of development, which means it will take several years before it reaches patients.