Daily pill from Eli Lilly leads to 15% weight loss in midstage study, rivaling Wegovy results without the shot

By Meg Tirrell, CNN

(CNN) — Eli Lilly’s experimental pill for weight loss helped people lose an average of 15% of their body weight after 36 weeks on the highest dose in a midstage trial, rivaling what’s seen with currently approved injectable therapies like Wegovy over longer durations.

The drug, orforglipron, had similar side effects as others in the class, known as GLP-1 receptor agonists: primarily gastrointestinal events like nausea, constipation and vomiting, researchers reported in a study published Friday in the New England Journal of Medicine. Results from the Lilly-funded trial were also presented at the American Diabetes Association conference in San Diego.

Currently approved medicines for weight loss like Novo Nordisk’s Wegovy are given as once-weekly injections. Novo Nordisk’s Ozempic, which contains the same key ingredient as Wegovy, called semaglutide, and Lilly’s Mounjaro are both approved for Type 2 diabetes but used off-label for weight loss. Orforglipron is part of a new group of experimental medicines that goes after the same target, GLP-1, but in a daily pill form.

“The optionality for patients is really important,” said Dr. Nadia Ahmad, Lilly’s associate vice president overseeing development of drugs for chronic weight management.

She noted that weight loss with orforglipron didn’t appear to plateau at the 36-week mark in the trial and said later-stage studies are underway to test the drug for longer to assess its full efficacy.

The 15% weight loss seen with the highest of four doses tested in the study, though, is important because that range is where “you’re really starting to potentially impact some of the other complications that beset these patients with obesity,” she said.

The medicine was tested in 272 people with an average starting body weight of 108.7 kilograms, or about 240 pounds. The trial enrolled patients with obesity, gauged by a body mass index of 30 or more, or overweight, with a BMI of at least 27, and a weight-related health condition. It tested four doses ranging from 12 to 45 milligrams, compared with placebo. The participants also got counseling on diet and exercise.

Weight loss at 36 weeks ranged from 9.4% to 14.7%, compared with 2.3% on placebo, the results showed. Participants on the medicine also had positive effects on levels of triglycerides and cholesterol, as well as systolic blood pressure, or the measure of pressure when the heart beats. There was no meaningful change in diastolic blood pressure, measuring pressure when the heart rests between beats.

Side effects including nausea, constipation, vomiting and diarrhea were most common, the study showed. Although most were “mild to moderate” in severity and happened as the participants gradually increased their dose of the medicine, between 10% and 17% stopped taking the drug because of them, the study found.

The researchers, led by Dr. Sean Wharton of Wharton Medical Clinic, noted in the NEJM paper that the study was designed to help figure out the best dose and method of increasing dose over time for larger, later-stage studies.

One limitation, the researchers noted, is that 91% of participants in the trial were White. Ahmad said it’s a goal for Lilly and the drug industry more broadly to achieve better diversity in clinical trials, and she noted that phase 3 studies of another Lilly medicine have better representation from more groups.

Lilly’s is just one of a crop of experimental weight loss drugs seeking to join blockbusters like Wegovy on the market. Novo Nordisk reported results last month showing that a pill version of semaglutide yielded 15% weight loss over 68 weeks, similar to Wegovy’s results. It provided a fuller look at those results, from a phase 3 trial, over the weekend.

But that drug, which is approved as Rybelsus for Type 2 diabetes, can be complicated to take, doctors say, with strict requirements about not eating or drinking within 30 minutes of taking it.

Pfizer said Monday it had chosen one of two oral GLP-1 drugs to continue developing, while discontinuing the other because of potential interactions with other medications and elevated liver enzymes. It published data last month on the one it’s taking forward in people with type 2 diabetes, called danuglipron; it also led to weight loss over 16 weeks that researchers said was comparable to other drugs in the class. It hasn’t shown a risk for elevated liver enzymes. The experimental medicines from Pfizer and Lilly are designed to be able to be taken with or without food.

The medicines still need to complete larger-scale testing in phase 3 trials, which means they are months to years from reaching the market.

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