Eli Lilly’s next-generation obesity drug retatroid clears Phase I diabetes trial

Eli Lilly It said Thursday that its next-generation obesity drug retatrotide has cleared its first late-stage trials in type 2 diabetes patients, helping them manage 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% at different doses over 40 weeks compared to placebo, meeting the study’s main objective. Patients began the trial with an A1c of 7% to 9.5%, and were not taking other diabetes medications.

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

Type 2 diabetes patients have historically struggled to lose weight, so Lilly was “very pleased” to see that the drug led to competitive reductions in blood sugar levels and significant weight loss, Ken Caster, Lilly’s director of cardiometabolic health, said in an interview.

The company was also “very pleased” with the relatively low discontinuation rate due to side effects, which was as low as 5%, he added.

These 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 retatrotide as the next pillar of its obesity portfolio after its weight-loss injection Zipbound and its next pill, Yaforglipron.

But Lilly has yet to file for drug approval for obesity or diabetes. The company expects to report findings from seven additional Phase 3 trials on the drug by the end of the year.

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

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

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 that having options in the obesity and diabetes space will be important because “not everyone will be helped or satisfied with the same treatment.” He added that which drug to choose will depend on “the solutions and the individual tailoring of the patient”, especially in the treatment of their diabetes.

For example, Custer said patients who want to regulate their blood sugar can benefit from Zipbound or Retrotide. But if they’re looking to lose more weight, the latter may be the best option, he said.

In two separate diabetes trials, ZipBound helped patients lose less weight than retatrotide. In a study called SURPASS-2, the highest dose of Zepbound helped patients lose an average of 13.1% of their body weight over 40 weeks. In another study, SURPASS-1, the highest dose helped patients lose 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 a predominantly gastrointestinal side effect. About 26.5% of patients experienced nausea at the highest dose, while approximately 22.8% and 17.6% had diarrhea and vomiting, respectively.

A low rate of patients experience dysesthesia, which is an unpleasant nerve sensation.

Dubbed a “triple G” drug, retatretide works by targeting three hunger-regulating hormones — GLP-1, GIP and glucagon — as opposed to just one or two of the current treatments. It 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’s semaglutide, the active ingredient in Vigovi, only mimics GLP-1.

As Retatrotide inches closer to market, Novo is racing to catch up to 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.

The newly discovered drug is a clear potential competitor to retatretide because it uses a three-pronged approach to both weight loss and blood sugar regulation. But the new treatment is very early in development, meaning it will be several years before it reaches patients.