Reaching or nearing your goal weight is a banner day. But if you were taking a glucagon-like peptide-1 receptor agonist (GLP-1) medication to help with your weight loss, you might be wondering what happens when you stop taking Ozempic or another GLP-1 drug. Is regaining Ozempic weight loss inevitable…or are there steps you can take to keep off the pounds?
For answers to these and other questions, Bottom Line Personal turned to Osama Hamdy, MD, PhD, medical director of the Obesity Clinical Program at Joslin Diabetes Center and associate professor of medicine at Harvard Medical School.
The Weight-Loss Rollercoaster
The big issue for most people who have lost weight—no matter how they did it—is keeping off the pounds. More than half of the weight lost without the help of a GLP-1 medication was regained within two years…and more than 80% after five years, according to an analysis of 29 long-term weight-loss studies.
For people who have struggled with conventional weight-loss methods, GLP-1s—including semaglutide (Ozempic, Wegovy), tirzepatide (Mounjaro, Zepbound) and others—have made a remarkable difference. But recent studies have shown that regaining the weight lost with the help of a GLP-1 medication can be as common as it is for weight lost using other methods.
The SURMOUNT-4 study, done by researchers at Weill Cornell Medicine, University of Glasgow, University of Texas Center for Obesity Medicine and Metabolic Performance, and other institutions compared the effects of stopping Zepbound to staying on it. Result: Participants who stopped taking the drug regained about half of what they had lost within one year, while those who continued treatment lost an additional 5.5% of their body weight.
In another study—the STEP 1 trial extension conducted by researchers at University of Liverpool, University College London and other institutions—people who stopped taking Wegovy regained two-thirds of the weight they had lost at the end of one year.
And in the STEP 4 trial on Wegovy, researchers found that those who continued to take the drug for about a year after achieving a mean weight loss of 10.6% over 20 weeks lost an additional 7.9%, while those who stopped taking it gained back 6.9%.
All of these results were true even when the participants actively tried to maintain their weight loss with diet and exercise.
Another concern: The weight regain didn’t show signs of stopping. It was just a matter of time before participants would regain even more of their lost weight.
The Odds of Regaining Weight
Each person’s weight-loss journey is different. A small number of people will keep off the lost weight, but we don’t yet know what percentage of people that is.
The current Surmount Maintain trial is ongoing until May 2026 at multiple sites across the country. Its objective is to compare participants who were taking Zepbound for one year and then randomized to stay on their maximum dose of medication…go to a lower maintenance dose…or go off their medication entirely.
Limitations of GLP-1s
GLP-1 drugs are designed to jump-start your weight loss, help you stick with your chosen dietary intervention and help you achieve your weight-loss goal. The idea behind these medications is to reduce appetite, but if you take the medication “passively”—meaning that you think the medication will do all the work for you—then once you stop taking it, you likely will gain all the weight back if you haven’t made active changes to your lifestyle. The medication is not an alternative to cutting calories and increasing exercise…but a complement to them.
Keep in mind: You will not lose excess weight unless you reduce your caloric intake. Important: Some GLP-1 medications, such as Mounjaro and Zepbound, also increase energy expenditure because they combine GLP-1, which shuts down appetite, with glucose-dependent insulinotropic polypeptide (GIP), which stimulates glucagon and energy expenditure. But once you stop taking the medication, that benefit stops.
Also remember that when you lose weight, your brain will reduce your basal metabolic rate—in other words, you will burn fewer calories during your rest or sleep. If you don’t take steps to limit the loss of muscle mass, you will burn even fewer calories (it takes more calories to maintain muscle than fat). In this scenario, if you go back to eating even half of what you used to eat, you will regain lost weight…and you even may regain beyond your baseline because the weight that goes back on isn’t the muscle you lost but mostly fat. You can develop what is called sarcopenic obesity—muscle loss and fat gain.
Studies from before the introduction of GLP-1 drugs have shown that people can maintain a weight loss for 15 years or more if, from the beginning, they keep up their muscle mass. Studies are underway now, including ones at Joslin Diabetes Center, to see if the muscle mass lost from GLP-1s can be mitigated with higher protein intake or a protein supplement plus strength training. In the meantime, here is what to do if you are taking a weight-loss medication…
- Start lifestyle interventions at the same time you start taking the medication or, if you are already on one, start right away (and definitely before you stop taking the medication).
- Increase activity in general—be more active.
- Increase focused exercise, a combination of strength training and cardio.
- Watch your calories, prioritizing protein and whole foods.
- Choose a diet plan to follow with the help of your doctor and make it a habit so you can maintain long-term weight loss.
Exploring Your Options
To see if you could go off your GLP-1 medication, work with your health care provider to progressively reduce the dosage. If you reach your weight-loss target with the maximum dose, de-escalate the dose until you find the smallest dose that lets you maintain the weight loss.
On the horizon: In the future, you may be able to switch to a pill form of the drug for maintenance or as a bridge before stopping—Eli Lilly’s pill orforglipron may be approved by the end of this year. And the Novo Nordisk drug cagrilintide, which has less effect on muscle while decreasing fat, could lower the risk for sarcopenia and possibly be safer to take long term—it is in a phase 3 trial now.
Still unclear: How long you can stay on a GLP-1 if you don’t have diabetes. There is no data yet from clinical trials beyond 72 weeks.
Reassess Your Weight-Loss Goals
People’s weight-loss goals often are unrealistic and near impossible to achieve. Example: It is unrealistic to think you can get back to your high school weight—you were still growing back then, and your muscle mass and bone, even your organs, have become heavier.
Another problem: Many practitioners rely on body mass index (BMI) to gauge body fat, but this is a very imprecise measurement. Ask your doctor if your body composition measurements can be done using a DEXA scan or bioelectric impedance analysis (BIA), which uses electrodes and a small current to calculate the distribution of fat and muscle mass. These measurements can be used to help monitor how much fat you’re losing versus muscle. Goal: When people lose weight, their muscle-mass-to-fat-mass ratio should go up, not down.
Strategy: Create a SMART goal—that’s the acronym for Specific—what you want to accomplish…Measurable—have concrete criteria to track progress…Achievable—you have the necessary resources and time to accomplish them…Relevant—a goal that really matters to you…and Time-bound—with a specific time frame to create a sense of urgency.
