A Mounjaro syringe tube rests against a boxShare on Pinterest
Mounjaro injection pen on display at Rachel Graham’s home in Carlsbad, California. Image credit: The Washington Post/Getty Images
  • Taking tirzepatide (Mounjaro and Zepbound) long-term may be critical for maintaining weight loss promoted by the drug, a new study finds.
  • Both people taking the drug and a control group taking a placebo maintained some weight loss during the study period, but those on the drug kept more off or lost additional weight.
  • Researchers say the study underscores the importance of making lifestyle changes in tandem with weight loss drugs.

People who continue to take the weight loss drug tirzepatide experience better results both with losing weight and keeping it off compared to those who take the drug for a limited duration, a new study finds.

Previous phase three clinical trials showed that tirzepatide, which is sold under the brand names Mounjaro and the recently approved Zepbound, resulted in a 20% or greater weight loss after 72 weeks compared to a control group that was taking a placebo.

This new phase three trial took 670 participants and lasted a total of 88 weeks. All participants received treatment with tirzepatide for 36 weeks. Then, participants were randomly assigned to either an an additional year of treatment or to a placebo injection.

The researchers reported that those who remained on the drug lost an additional 5% of their total weight, adding up to around 25% overall. While the placebo group maintained some weight loss although they gained 14% of their weight back, the researchers at the Weill Cornell Medicine and NewYork-Presbyterian in New York reported.

The study was sponsored by Eli Lilly and Company, the manufacturer of both Mounjaro and Zepbound.

Tirzepatide belongs to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists, which includes drugs such as semaglutide, which are sold under the names Wegovy and Ozempic.

However, tirzepatide differs from semaglutide in some important ways.

“Tirzepatide is a single molecule that binds to and activates not only the GLP1 receptor but also a second receptor—the glucose-dependent insulinotropic polypeptide (GIP) receptor,” explained Dr. Dan Maselli, an obesity medicine physician and bariatric endoscopist at True You Weight Loss in Atlanta who was not involved in the study.

“GIP receptor activation has similar effects as activation of the GLP1 receptor, and the synergistic effect from this dual-binding likely explains why weight loss from tirzepatide is more significant than weight loss from semaglutide,” he told Medical News Today.

Experts say that additional weight loss benefit could help people feel like it’s worthwhile to stay on the drug.

“This study is consistent with other studies that there is a high rate of recidivism with weight loss patients when they stop medication,” said Dr. Mir Ali, a bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in California who was not involved in the study.

“Studies have shown that tirezepatide has more weight loss than other medications, even Ozempic. When patients see good weight loss results, they are more likely to continue the treatment plan,” he told Medical News Today.

This drug, as with other similar drugs, sees most of the weight loss in the initial months after starting treatment.

After that, losses are incremental, so a study demonstrating the importance of remaining on the drug for weight loss maintenance is critical, experts say.

“The trial was instructive about the capabilities and limitations of tirzepatide,” Maselli said. “We can see here that over the course of the following year, subjects continue not only to lose weight but also see improvements in measures of cardiometabolic disease — such as insulin resistance (e.g. hemoglobin A1c), cholesterol, body mass index, and waist circumference. In concert, these findings show that tirzepatide is a formidable tool for those seeking treatment for obesity.”

However, while it might be tempting to say that it’s not a surprise that a study sponsored by a drug manufacturer might find that staying on the drug long-term is the best course of action, most experts consulted said the quality of the study was sound.

“This study was sponsored by and written mostly by Eli Lilly employees and the lead and other authors also have very strong ties to the pharmaceutical industry with many conflicts reported,” noted Dr. Meredith Warner, a Baton Rouge, Louisiana, orthopedic surgeon and founder of The Well Theory who wasn’t involved in the study.

But overall, Warner told Medical News Today, “the study had good power and there seem to be no issues with the statistical analysis.”

Instead, the study in part affirmed what doctors say they already know about weight loss.

“[The study] reinforced that obesity is a chronic, complex, progressive, and relapsing disease state and that these medications are treatments but not cures,” Maselli said. “By the time the 88 weeks was up, subjects in the placebo arm from week 36 to 88 had regained over half of the weight they had lost from weeks 0 to 36 on the tirzepatide. This underscores what medical professions in obesity medicine have understood in the wake of the semaglutide literature: these medications must be continued long-term to sustain improvements in weight and cardiometabolic disease.”

“This, of course, is frustrating for patients to hear, as many are looking to truncate and not add to their medication list, least of all for a medication that, in the current landscape, is associated with significant out-of-pocket expense and supply disruptions that lead to unpredictable access.”

That said, lifestyle changes also play an important role in restoring metabolic health, and no drug or medical procedure is a cure-all.

“No matter what intervention is employed, if the patient does not make permanent, long-term dietary and lifestyle changes, they can regain weight,” Ali said. “Medications and surgery are tools to help patients make these changes; like any other tool if used properly, it can work well.”