Eli Lilly's Next GLP-1 Drug Outperforms Zepbound
By Reuters | 11 Dec, 2025

The market leader in weight-loss drugs is poised to strengthen its position when its retatrutide drug is approved by the FDA.

Eli Lilly said on Thursday its next-generation obesity drug helped patients lose an average of 28.7% of their weight in a late-stage trial, outperforming its blockbuster drug Zepbound and reinforcing the company's lead in the fast-growing market.

The global obesity market has surged in recent years on strong demand for GLP-1-based drugs like Zepbound and Novo Nordisk's Wegovy, prompting drugmakers to invest heavily in next-generation treatments that could deliver faster, deeper, or more durable weight loss.

BMO Capital Markets analyst Evan Seigerman called it the "highest weight loss to date", adding it may surprise investors with the magnitude of weight reduction demonstrated.

The once-weekly injected drug, retatrutide, is designed to mimic the action of the GLP-1 hormone, which helps regulate blood sugar, slow stomach emptying and decrease appetite.

Lilly, in its first late-stage trial readout, said the highest dose of the drug delivered weight loss of up to an average of 71.2 pounds at 68 weeks, along with substantial relief from deep-aching joint pain when tested in participants with obesity and osteoarthritis of the knee.

TRIAL DEPARTURES ATTRIBUTED TO EXCESSIVE WEIGHT LOSS

Lilly said that perceived excessive weight loss, particularly among those with lower body mass indexes (BMI) at the start, was behind some choosing to leave the trial.

About 18.2% of patients who received the highest dose discontinued the trial, compared to 4% on placebo. Among people whose BMI was greater than 35, the discontinuation rate was 12.1% for the highest dose versus 4.8% for placebo.

J.P. Morgan analyst Chris Schott said retatrutide tolerability was somewhat worse in the trial than what was reported for Zepbound but said it was "not surprising". 

Overall, side effects were in line with those typically seen in weight-loss treatment trials, the company said, including gastrointestinal issues such as nausea, diarrhea, constipation and vomiting. 

Dysesthesia, an abnormal skin sensation, occurred in 20.9% of patients on the highest dose.

Seigerman said dysesthesia rates were "elevated" and that he would look to full data to be presented to better assess the severity of these events. 

Shares of Lilly, which last month became the first drugmaker to hit the $1 trillion valuation, rose 2.5% in morning trade. 

"Lilly is not up that much today, which I think confirms that the overall profile of retatrutide in this study seems indeed somewhat mixed, versus its expectations", said Kepler Cheuvreux analyst David Evans. 

IMPACT ON KNEE PAIN

Lilly said a post-hoc analysis of the data showed that participants' pain scores were reduced by up to an average of 4.5 points, with more than 1 out of 8 patients free from knee pain at the end of the trial.

The company said on Thursday seven late-stage trials evaluating the drug in obesity and type 2 diabetes are expected to be completed in 2026. 

"For Lilly, this is likely another blockbuster drug with a long patent duration and adds to a full suite of solutions that physicians can tailor to individual patient needs," said Kevin Gade, chief operating officer at Lilly shareholder Bahl and Gaynor.

Retatrutide activates three hormone receptors - GLP-1, GIP and glucagon - earning it the nickname "triple G". Triple-G weight loss drugs are expected to produce greater weight loss than earlier generations by combining appetite suppression, blood sugar control and increased calorie burning. 

Rival Novo is also developing a "triple-G" weight-loss drug candidate UBT251 after securing global rights from China-based United Laboratories International as a follow-on to semaglutide, its highly popular drug sold as Ozempic and Wegovy.

There have been significant investor expectations around retatrutide after mid-stage data demonstrated up to 24.2% weight loss after 48 weeks, surpassing results seen with other obesity drugs. 

Wegovy and Zepbound have been shown in trials to produce weight loss of about 15% and 20% or more. 

(Reporting by Sriparna Roy, Mrinalika Roy and Christy Santhosh in Bengaluru, additional reporting by Boleslaw Lasock; Editing by Sriraj Kalluvila)