Eli Lilly says next-generation weight loss drug clears crucial obesity trial

Eli Lilly on Thursday said its next-generation drug cleared a crucial late-stage trial in patients with obesity, delivering significant weight loss across doses. 

The results bring Lilly one step closer to filing for approval of the weekly injection, called retatrutide, which works differently from existing shots and pills from both Lilly and Novo Nordisk. It also appears to be more effective than those options.

The highest dose of retatrutide helped patients lose 28.3% of their weight — or 70.3 pounds — on average over 80 weeks, compared with 2.2% with placebo, when evaluating only patients who stayed on the drug.

Roughly 45% of the 2,500 patients in the Phase 3 trial achieved 30% or more weight loss, Lilly said. 

The highest dose also helped patients with a body mass index of 35 or above who participated in an extension of the study lose 30.3% of their weight on average over 104 weeks. That BMI threshold puts people at higher risk of cardiovascular complications or diabetes.

While the drug appeared to show higher rates of certain gastrointestinal side effects, such as nausea and diarrhea, especially at the highest dose, they were generally consistent with a previous Phase 3 trial of retatrutide in patients with obesity and a type of knee arthritis pain. Some analysts previously said those side effects highlight the speed and strength of the drug’s weight loss.

A lower dose of retatrutide that Lilly tested in the latest study was also associated with fewer discontinuations due to side effects.

Dan Skovronsky, Lilly’s chief scientific and product officer, called the 30% weight loss an “incredible number to see,” as it has previously only been associated with bariatric surgery. 

“We haven’t seen that level of weight loss before with these kinds of medicines,” Skovronsky told CNBC in an interview. 

Around 65% of people taking the highest dose of retatrutide also achieved a BMI of less than 30, which falls under the threshold for obesity, at 80 weeks.

Ahead of the results, some analysts said they were expecting to see weight loss higher than that seen with Lilly’s blockbuster weight loss drug Zepbound, which is around 20% to 22%. 

The data is the third late-stage result to date on retatrutide, which succeeded in a diabetes trial earlier this year and cleared a smaller study on patients with obesity and a type of knee arthritis in December. Lilly is betting big on retatrutide as the next pillar of its obesity portfolio after its injection Zepbound and newly launched pill, Foundayo. 

In a January note, TD Cowen analysts estimated that retatrutide could rake in sales of $3.8 billion in 2030. 

Retatrutide is also critical to the drugmaker’s plan to maintain its market share majority over Novo in the booming market for weight loss and diabetes drugs. Some analysts estimate the segment could be worth about $100 billion by the 2030s. 

Notably, Lilly also tested a lower 4-milligram dose not used in other trials, and it helped patients lose 19% of their weight, or 47.2 pounds, over 80 weeks. 

Skovronsky said the weight loss seen with that lowest dose is similar to that of Zepbound at high doses, but “with a really excellent tolerability profile” that exceeded Lilly’s expectations. That refers to how well patients handle the drug – a key metric in trials on medicines containing GLP-1s, which often bring gastrointestinal side effects.

The number of patients at the 4-milligram dose who discontinued treatment due to side effects was lower than the placebo group, which Skovronsky called “remarkable to see.” Around 4% of patients on that dose stopped the drug due to side effects, compared with nearly 5% with the placebo.

That compares with a discontinuation rate of 11.3% among patients who took the highest dose.

Still, Skovronsky said, “I think we’re making history here, both on the high end with the high dose and on the low dose for what we can offer patients.”

“For some patients, 30% weight loss may be more than what they’re seeking,” Skovronsky later added. “For other patients, that may be what they need to get healthy. So not everyone will go up to the highest dose level and stay on it for two years.”

The safety data on Lilly’s drug was consistent with other GLP-1-containing medications, with the most common side effects being gastrointestinal.

Around 42% of patients on the highest dose experienced nausea, while roughly 32% and 26.1% had diarrhea and constipation, respectively. More than 13% of patients on that dose also experienced an upper respiratory tract infection, a contagious illness affecting the nose, sinuses and throat.

Meanwhile, more than 12% of patients on the highest dose also experienced dysesthesia, which is an unpleasant nerve sensation observed in previous trials of the drug.

Ahead of the results, some analysts said they were watching to see if retatrutide would cause any cardiac issues, such as arrhythmia, an irregular heartbeat. That’s because the drug works by targeting three gut hormones, including one called glucagon, which increases energy expenditure. 

But Lilly said it did not observe any cardiac or liver issues. The company did notice a slightly higher rate of urinary tract infections in people on the drug compared with placebo, but most were mild and resolved while people stayed on treatment, Skovronsky said. More than 8% of patients at the highest dose had a UTI.

He said it’s unclear why more patients had UTIs, but that the side effect is also seen with bariatric surgery, so it may be the result of “the velocity of weight loss” people experience. 

Dubbed the “triple G” drug, retatrutide targets 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.

Lilly held a 60.1% share of the U.S. obesity and diabetes drug market in the first quarter, according to an earnings presentation, while Novo’s market share in the period was 39.4%.

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 International. 

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.