Overweight or obese participants without type 2 diabetes who took the drug, called tirzepatide (sold as the diabetes drug Mounjaro), lost an average of nearly 21 percent of their body weight at the highest dose studied. Scientists presented their findings at the American Diabetes Association (ADA)’s annual meeting in New Orleans and published the study in The New England Journal of Medicine. “Definitely, the weight loss in this study is far more what we had ever seen with other FDA-approved medications in term of the absolute amount of weight lost or percentage of weight lost,” says Osama Hamdy, MD, PhD, an associate professor at Harvard Medical School and medical director of the obesity clinical program at the Joslin Diabetes Center in Boston. Dr. Hamdy wasn’t involved in the new trial; he has received funding from Eli Lilly, the maker of tirzepatide.
Analyzing Tirzepatide for Weight Loss
The trial enrolled 2,539 adults who weighed an average of 231 pounds and had a body mass index (BMI) of 38 to start. A BMI of 30 or higher is considered obesity, and 95 percent had a BMI at least this high. Participants were randomly assigned to receive 72 weeks of once-weekly injections of placebo or one of three doses of tirzepatide — 5 milligrams (mg), 10 mg, or 15 mg. At the highest dose, people lost an average of 20.9 percent of their body weight by the end of the trial, or about 52 pounds. Their average weight loss, 19.5 percent, was the equivalent of about 49 pounds, with the 10 mg dose, and 15 percent, or about 35 pounds, with the 5 mg dose. Most side effects were mild to moderate, and most often involved gastrointestinal issues such as nausea, diarrhea, and constipation; roughly 4 to 7 percent of participants discontinued treatment due to drug-related side effects. This was a phase 3 clinical trial, which is typically the final stage of testing required to be considered for U.S. regulatory approval. “These results are an important step forward in potentially expanding effective therapeutic options for people with obesity,” says lead study author Ania Jastreboff, MD, PhD, an associate professor at Yale University School of Medicine and codirector of the Yale Center for Weight Management in New Haven, Connecticut. “Notably, about 9 out of 10 individuals with obesity lost weight while taking tirzepatide,” says Dr. Jastreboff, who has financial ties to several pharmaceutical companies, including Eli Lilly, maker of tirzepatide and funder of the new clinical trial. The U.S. Food and Drug Administration (FDA) approved tirzepatide in May to help manage blood sugar in people with type 2 diabetes; the diabetes treatment is called Mounjaro. A head-to-head clinical trial found tirzepatide in this setting to be more effective at controlling blood sugar and spurring weight loss in type 2 diabetes patients than semaglutide (Ozempic), an injected GLP-1 receptor agonist, or two commonly used forms of insulin, according to the FDA. In this earlier trial, tirzepatide reduced so-called hemoglobin A1C levels, which reflect average blood sugar levels over about three months, by 0.5 percent more than semaglutide and by about 1 percent more than insulin, the FDA said. The 15 mg dose of tirzepatide helped type 2 diabetes patients with obesity lose 12 pounds more than semaglutide, and 27 to 29 pounds more than the two forms of insulin evaluated, the FDA noted.
Questions About Relative Efficacy, Price of Tirzepatide Linger
One drawback of the new trial of tirzepatide for obesity is that it didn’t directly compare this drug with other treatment options. Hamdy says head-to-head tests against semaglutide and another similar drug, liraglutide, will be needed to confirm whether tirzepatide is indeed the best medication for obesity. Hamdy has also received funding from Novo Nordisk, maker of semaglutide. Results from the new trial do suggest that tirzepatide at the highest dose may work as well as bariatric surgery, Hamdy notes. But if tirzepatide wins FDA marketing approval, how much patients use this drug may ultimately come down to is price. “Obesity is a serious disease that may lead to many costly complications, including diabetes, hypertension, and cardiovascular disease,” Hamdy says. He doesn’t expect tirzepatide to be cheaper than other new targeted weight-loss drugs like semaglutide (Wegovy) or liraglutide (Saxenda), which retail for more than $1,300 a month, according to prices on GoodRx. Because of all the health risks of obesity, and how much many patients struggle to lose weight and keep it off, more treatment options are still needed, says Clifford Rosen, MD, a professor at Tufts University School of Medicine in Boston and Mainehealth Institute for Research in Scarborough, Maine, who wasn’t involved in the study and has no financial ties to companies. “Nothing is wrong with the other interventions including the current GLP-1R agonists, and bariatric surgery,” Dr. Rosen says. “But if tirzepatide produces a similar magnitude of weight loss as bariatric surgery, that would be a huge advance and a great alternative to surgery.” Eli Lilly didn’t immediately respond to a request for comment on how soon the company may seek FDA approval of tirzepatide for obesity.
