Chances of Losing Weight Increases Over Time

Based on analysis of electronic health record data from more than 18,000 overweight or obese adults who were taking either one of the two drugs, researchers on the JAMA study found that those on tirzepatide were nearly twice as likely to achieve 5 percent weight loss, about two and a half times more likely to lose 10 percent of their body weight, and more than three times as likely to reach 15 percent weight loss.

After one year of treatment, weight loss of at least 5 percent was reached by nearly 82 percent of tirzepatide users compared with 66.5 percent of semaglutide users. About 62 percent of participants who took tirzepatide versus 37 percent of those on semaglutide achieved at least 10 percent weight loss, and 42 percent of those on tirzapatide lost 15 percent or more of their body weight compared with 18 percent in the semaglutide group.

Patients on tirzepatide also experienced significantly larger reductions in body weight over time.

At three months, individuals on tirzepatide saw an average body weight drop of 6 percent compared with less than 4 percent for those who took semaglutide. By one year, however, the weight loss difference was almost twice as great, with an average loss of 15 percent for tirzepatide and 8 percent for semaglutide.

“I would say that based on study results, tirzepatide is currently the best for weight loss, but semaglutide works really well, too,” says Sun Kim, MD, an endocrinologist who specializes in the treatment of type 2 diabetes and is an associate professor of medicine at Stanford University in California. “Some patients don’t do as well on one drug compared to the other. They both function really well, but one may have better results.”

What’s Behind the Difference?

Both semaglutide and tirzepatide are in a class of drugs called glucagon-like peptide-1 (GLP-1) agonists. These medications mimic GLP-1, a hormone made in the small intestine that helps lower blood sugar, decreases appetite, and makes a person feel fuller (satiety).

The latest study findings were based on outcomes from patients prescribed either Ozempic or Mounjaro, because at the time of the study, tirzepatide had not yet been approved for weight loss.

While both drugs are GLP-1 agonists, tirzepatide has an extra ingredient that may explain its greater potency.

“The drug incorporates an additional gastrointestinal hormone [a GIP or glucose-dependent insulinotropic polypeptide receptor agonist] that impacts insulin sensitivity and brain signaling to aid with satiety,” says Farah Husain, MD, the division chief of bariatric surgery at the University of Arizona College of Medicine Phoenix and the medical director at Banner University Medical Center. “The addition of the new hormone component is likely the reason it is performing superiorly.”

Weighing the Pros and Cons

When it comes to selecting the medication that will best suit your needs, Dr. Husain recommends talking to your primary care provider and possibly seeing an obesity medicine specialist.

“It’s very important to understand a patient’s medical problems, other medications, allergies, and history to choose the appropriate medication,” Husain says.

While both Ozempic and Mounjaro are self-administered in once-weekly injections, Dr. Kim notes that semaglutide now also comes in tablet form to be taken orally. Called Rybelsus, the medicine is approved as a diabetes treatment but may help with weight loss.

Adverse events related to the medications tirzepatide and semaglutide are very similar, according to Johanna Finkle, MD, an obstetrician and gynecologist with the University of Kansas Health System in Kansas City.

“The side effects are primarily nausea, vomiting, and constipation,” she says, warning that in some cases these medications can cause slow gastric emptying, worsen certain GI conditions such as gastroparesis, and other rare but serious side effects.

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Although the results were determined from a large population, the study authors stress that more work is needed to compare the effects of tirzepatide and semaglutide on other key end points, such as reduction of major cardiac events.