What Happens When People Stop Taking the Weight Loss Drug Zepbound

As a new generation of highly effective weight loss drugs hits the market, doctors are still trying to figure out how long people will need to take them for the best results.

A new study offers a clue. Writing in JAMA, researchers report on what happens when people stop taking the weight loss drug tirzepatide, known as Zepbound. Tirzepatide can help people lose double digit percentages of their body weight, compared to single digit percentages with diet and exercise.

The study, sponsored by the drug’s manufacturer, Eli Lilly, included 670 people with a body mass index (BMI) of 30 or higher, or with a BMI of at least 27 and one weight-related health complication other than diabetes. Everyone took tirzepatide for nine months, and then were randomly and blindly assigned to continue taking the drug or start taking a placebo for a year. Doctors provided all of the participants with diet and exercise support throughout the study.

After nine months on the drug, people lost an average of 20.9% of their body weight. Those who continued on the medication lost an additional 5% of their original body weight over the next year—but those who took a placebo gained 14% of their body weight back. Any improvements they had made in measures like blood pressure, cholesterol levels, and waist circumference also started to wane.

“Just like diabetes, hypertension, hyperlipidemia, and many other metabolic diseases, the results show that chronic treatment of some type is going to be necessary in order to maintain all the benefits of weight loss achieved with the treatment,” says Dr. Louis Aronne, director of the comprehensive weight control center at Weill Cornell Medicine and lead author of the study.

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But the benefits didn't disappear as soon as people stopped taking tirpzepatide. Even a year after stopping, people still didn’t return to their original weight, and they continued to improve in some areas, such as becoming more sensitive to insulin, reducing their risk of diabetes, and having healthier triglyceride levels. “This tells us that chronic treatment is going to be necessary for optimal outcomes but that all of the benefit is not lost immediately if people stop taking that treatment,” says Aronne.

Since tirzepatide was just approved in November, it’s still too early to know how long people might need to take the medication, and how it can best fit into a weight loss program. "What if some people go to a lower dose of the medicine, or take it less frequently, or have more intensive behavioral or nutritional interventions? Will they be better able to maintain their weight loss?" Aronne says. "All of those things are possible; we’ll just have to wait and see.”

What is clear now is that pairing the drug with diet and exercise is likely to help people lose the most weight and keep it off. It’s possible that the initial weight loss the medication causes could jump start physiological changes that will make it easier for people to adjust their eating habits and become more physically active. “What these medicines do is they tend to help people comply with a good diet; they are not as hungry and may not have the same cravings,” says Aronne. Tirzepatide isn't meant to replace healthy habits, "but to help make those habits better.”