Pounds Return Once Zepbound Users Quit the Weight-Loss Drug: Study

Folks who take the blockbuster weight-loss med tirzepatide (Zepbound) may regain much of the weight they lost soon after discontinuing it, new research shows.

A trial funded by Eli Lilly, the injected drug’s maker, found that “in patients with obesity or overweight, withdrawing tirzepatide led to substantial regain of weight.”

On the other hand, continuing on with tirzepatide kept the weight off, over the full two years of the trial.

Of course, sticking with drug could mean big bills for users.

Medicare and Medicaid do not cover the drug, and if your private insurance doesn’t cover Zepbound, it can cost over $1,000 per month. Lilly says certain commercial card savings programs it offers can reduce the monthly cost to about $550, or even lower, however.

Zepbound was approved for weight loss by the U.S. Food and Drug Administration on Nov. 8, and Lilly announced its availability to consumers on Dec. 6.

To trigger weight loss, tirzepatide mimics two hormones, GLP-1 and GIP, which stimulate the release of insulin in the body. It quells appetite and slows the rate at which food moves through the stomach, helping patients feel full.

It’s the first drug in its class to compete with another weight-loss blockbuster, Wegovy.

Wegovy, made by Novo Nordisk, uses a similar active ingredient, semaglutide, which only focuses on GLP-1.

That difference appears to translate to greater weight loss with Zepbound than Wegovy, a recent study found. Zepbound has been found to prompt up to a 20.9% drop in weight at higher doses, while Wegovy patients typically see a 15% reduction in weight.

But if patients quit Zepbound, does the weight come back?

Yes, according to the new study, which was led by Dr. Louis Aronne, a professor of clinical medicine at Cornell University. He also directs the Comprehensive Weight Control Center at Weill-Cornell Medical Center, in New York City.

The research involved 670 overweight or obese people without diabetes who averaged 48 years of age. About 70% were women.

All participants first took tirzepatide for nine months. Then some were randomized to either another year taking the drug, or to a year taking a “dummy” placebo. Neither the participants nor researchers knew whether a participant was taking the active drug or the placebo.

By the end of trial, nearly all (89.9%) of the those who got tirzepatide for all 22 months maintained at least 80% of the weight loss they’d already experienced by the nine-month mark, Aronne’s group reported.

However, that was only true for about 17% of participants who’d been switched over to the placebo shot at the nine-month mark.

By the study’s end, folks who’d stuck with tirzepatide lost a quarter (25.3%) of their baseline weight, compared to about 10% weight loss for those who’d stopped taking the drug at nine months.

The study was published Dec. 11 in the Journal of the American Medical Association.

Side effects could occur — people were more likely to experience “mild to moderate gastrointestinal events” while on tirzepatide long-term versus placebo, the team noted.

Aronne’s team also noted that the weight regain observed after stopping tirzepatide isn’t unique to the drug. At least four other trials focused on weight-loss drugs have found the same rebound effect after quitting, including one trial focused on semaglutide (Wegovy).

Together, the data suggests that “obesity is a chronic metabolic condition similar to type 2 diabetes and hypertension requiring long-term therapy in most patients,” Aronne’s team said.

More information

Find out more about new weight-loss medications at the American Medical Association.

SOURCE: Journal of the American Medical Association, Dec. 11, 2023