Many people struggling with obesity have seen impressive weight loss results using tirzepatide, a drug that works by controlling blood sugar, digestion, and appetite.
Sold under brand names like Mounjaro and Zepbound by Eli Lilly, tirzepatide is one of the most popular weight-loss drugs in the world. But what happens after people stop taking it?
A new study by Eli Lilly and researchers in the US and UK reveals that most people who stop taking tirzepatide gain back much of the weight they lost—and also lose the health benefits they had gained.
This study was published in JAMA Internal Medicine and focused on how weight regain after stopping tirzepatide affects things like blood pressure, blood sugar, cholesterol, and waist size.
Obesity is not just about extra weight. It is a long-term health problem linked to serious conditions like heart disease and diabetes. That’s why doctors aim to treat it by improving overall health, not just helping people lose weight.
Tirzepatide helps by lowering blood sugar, reducing hunger, and encouraging digestion. However, the key question is: do these benefits last after the drug is stopped?
In the study, researchers looked at data from 783 people with obesity. Everyone took tirzepatide for 36 weeks. After that, half continued the medication and the other half switched to a placebo (a fake drug).
The researchers followed the second group for another 52 weeks. They only studied the people in this group who had lost at least 10% of their body weight during the first phase—308 participants in total.
While taking tirzepatide, people lost an average of 21.9% of their weight. They also had major improvements in health markers: blood pressure went down, blood sugar levels improved, and cholesterol and insulin resistance dropped. Their waistlines also shrank by over 18 cm on average.
But after stopping the drug, things changed. Around half of the participants gained back 50% or more of the weight they had lost. One in four people gained back at least 75%. A small number even ended up heavier than when they started. Only 4% continued to lose weight after stopping the medication, relying on lifestyle changes alone.
Health benefits also faded with the weight regain. People who gained the most weight back saw their blood pressure, cholesterol, and blood sugar rise again—often close to their starting levels. The more weight someone regained, the more their health markers worsened.
Those who regained less than 25% of their weight still showed some lasting benefits. Their waist sizes and insulin resistance stayed mostly stable. However, even this small group saw some signs of their health beginning to reverse without the drug.
The study also found that HDL cholesterol—the “good” kind—dropped during tirzepatide treatment but rose again after stopping. One surprising finding was that β cell function (related to insulin production) decreased during and after treatment, which needs further study.
Overall, the message is clear: while tirzepatide can help people lose weight and improve their health, those benefits may not last if the drug is stopped. Obesity is a chronic condition, and short-term treatment may not be enough. Continued medication, combined with diet and exercise, might be needed for long-term success.
However, the study had limitations. It didn’t measure body composition, diet, or physical activity directly. Since it was funded by Eli Lilly, there may be bias in how the findings were interpreted.
Still, the research gives us an important insight: stopping tirzepatide often leads to weight gain and a return of health problems. People with obesity who benefit from tirzepatide may need to stay on it longer to keep those benefits going.
If you care about weight loss, please read studies that hop extract could reduce belly fat in overweight people, and early time-restricted eating could help lose weight.
For more health information, please see recent studies about a simple path to weight loss, and results showing a non-invasive treatment for obesity and diabetes.
Copyright © 2025 Knowridge Science Report. All rights reserved.
