Lilly's Experimental Shot Cuts Body Weight By 23% In Study

A next-generation obesity shot from Eli Lilly & Co. helped patients lose almost a quarter of their body weight, potentially making the experimental drug the most potent weight-loss medicine yet.

The late-stage study was designed to measure weight loss and pain associated with knee osteoarthritis, a condition closely linked to obesity. Patients on the highest dose of the drug — called retatrutide — lost more than 23% of their body weight in 68 weeks, Lilly said in a statement Thursday. Study participants experienced a more than 62% reduction in knee pain, according to a self-reported questionnaire. 

Wall Street was expecting the latest study to show weight loss of about 20% to 23%, with at least a 50% reduction in knee pain. The results exceeded expectations, with some patients losing so much weight they decided to drop out of the trial, Lilly said. The drugmaker’s shares rose 3% in trading before US exchanges opened. 

“We believe retatrutide could become an important option for patients with significant weight loss needs and certain complications, including knee osteoarthritis,” Kenneth Custer, president of Lilly Cardiometabolic Health, said in the statement.

The latest results will help cement Lilly’s dominance in the obesity market that’s expected to hit $100 billion by 2030. The company’s shot Zepbound is already the most popular weight-loss medication, but Lilly is racing to develop drugs that are more effective, easier to take or that offer benefits like fewer side effects.

The stakes for these next-generation compounds are high: rival Novo Nordisk A/S’s shares plummeted the most on record after an experimental shot fell short of expectations last year. The drug, CagriSema, helped patients lose an average of 20.4% of their weight — less than the 25% the drugmaker had promised. Novo trimmed gains to 2.2% in Copenhagen trading on Thursday.

The trial is the first of many studies Lilly is running to test retatrutide in obesity and other related conditions like cardiovascular disease and chronic kidney disease. The company expects to share results from those studies beginning next year. 

Retatrutide works by combining three different gut hormones — GLP-1, GIP and glucagon — giving it an edge over treatments like Zepbound and Novo’s Wegovy. Lilly has excelled at pioneering these types of combination molecules, which have been shown to elicit even greater weight loss.

Lilly’s latest trial lasted 68 weeks and enrolled patients with obesity and knee osteoarthritis, a condition characterized by pain, stiffness, and swelling in the knee joint due to the wear and tear of cartilage. It’s often linked to aging and obesity. 

The trial looked at the 9 milligram and 12 milligram doses of the medication, which both lowered markers of heart disease and blood pressure, the results show. Some patients were completely free of knee pain by the end of the trial, Lilly said. 

However, patients still experienced side effects, causing about 18% of people on the highest dose to drop out of the trial. The most common side effects were nausea, diarrhea and constipation. More than 1 in 5 patients on the higher dose experienced dysesthesia, an uncomfortable or unpleasant nerve sensation. Lilly said it was generally mild for patients and rarely led to treatment discontinuation.

Patients whose BMI was lower than 35 were more likely to drop out of the trial, including because they felt they lost too much weight, Lilly said. 

“Not all patients may need this potentially very high level of efficacy, and we believe retatrutide will likely be best suited for patients with a very high BMI, or with obesity related complications that require a high degree of weight loss,” Lilly’s Chief Scientific Officer Daniel Skovronsky said on a call with investors in October.