What happens when you stop a GLP-1 medication
What two withdrawal trials found about weight regain, what happened to blood pressure and cholesterol, how common stopping is, and what the maintenance evidence suggests.
What happens when you stop a GLP-1 medication?
Most people regain a large share of the weight, though not all of it within the first year. In the STEP 1 extension, people who stopped semaglutide regained about two-thirds of their lost weight within a year and ended 5.6% below their starting weight [1]. In SURMOUNT-4, people switched from tirzepatide to placebo regained 14.0% over a year, while those who stayed on lost another 5.5% [2].
Key numbers
- A year after stopping semaglutide, people in the STEP 1 extension had regained about two-thirds of the weight they lost, ending 5.6% below where they started [1].
- In SURMOUNT-4, people switched from tirzepatide to placebo regained 14.0% over a year, while those who stayed on lost another 5.5% [2].
- After stopping semaglutide, most improvements in heart-health markers drifted back toward where they started [1].
- In practice, only about a third to a half of people are still taking a GLP-1 at one year, and about 15% at two years [3].
How much weight do people regain after stopping semaglutide?
About two-thirds of what they lost, over a year. In the STEP 1 extension, 327 participants lost an average of 17.3% of their body weight over 68 weeks on semaglutide 2.4 mg, then regained 11.6 percentage points in the year after stopping, a net loss of 5.6% from where they began [1]. Their structured lifestyle program stopped at the same time as the drug.
Regain was still continuing when follow-up ended at week 120, and the extension was an exploratory analysis rather than a trial designed and powered to answer this question [1].
How much weight do people regain after stopping tirzepatide?
SURMOUNT-4 tested this directly. After 36 weeks on tirzepatide, participants had lost 20.9% of their weight; 670 were then randomized to stay on it or switch to placebo for a year. Weight changed by -5.5% with tirzepatide and +14.0% with placebo, and 89.5% of those who stayed on kept at least 80% of their loss, against 16.6% on placebo [2].
The placebo group did not return all the way: across the full 88 weeks it was still 9.9% below its starting weight, compared with 25.3% for those who continued [2]. The trial excluded people with diabetes.
What happens to blood pressure and cholesterol when you stop?
They tend to drift back too. In the STEP 1 extension, the cardiometabolic improvements seen during semaglutide treatment reverted toward baseline for most of the measures tracked in the year after stopping [1]. The authors concluded that ongoing treatment is needed to maintain improvements in both weight and health.
How common is stopping a GLP-1?
Very common. The 2025 joint advisory from four medical and nutrition societies reports that in practice only about 33% to 50% of people are still taking a GLP-1 at one year, and about 15% at two years [3]. That means most people who start one will eventually face the question of what comes next.
How do you plan for stopping a GLP-1?
Start with your prescriber, since stopping is a medical decision and neither trial tested a gradual taper. Then build the habits the advisory lists for long-term maintenance: regular physical activity of about 60 minutes a day, self-monitoring of weight, food and activity, keeping screen time under 10 hours a week, and coping strategies [3].
Muscle is worth protecting throughout: the advisory pairs adequate protein with strength training to preserve lean mass during treatment [3]. See our guide to protein on a GLP-1 medication.
Where Understory fits
Nothing we sell prevents weight regain, and we won't suggest otherwise. Understory's Protocol One is a daily vitamin, mineral and digestive supplement designed to be taken alongside a GLP-1 medication, for the nutrition and digestive-comfort side of treatment. It is not a weight-loss or weight-maintenance product.
What this evidence can't tell you
- The STEP 1 extension was exploratory, and the lifestyle program stopped at the same time as the drug, so the two effects can't be separated [1].
- SURMOUNT-4 excluded people with diabetes, and both trials followed people for about a year after stopping [2, 1].
- Both trials stopped the drug outright; neither tested a gradual taper or a lower maintenance dose.
- The maintenance habits come from an expert advisory, not from a trial of people coming off a GLP-1 [3].
Sources
- Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes, Obesity and Metabolism. 2022;24(8):1553-1564. doi:10.1111/dom.14725 PubMed. Exploratory off-treatment extension; 327 participants.
- Aronne LJ, Sattar N, Horn DB, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38-48. doi:10.1001/jama.2023.24945 PubMed. Randomized withdrawal trial; 670 randomized; people with diabetes excluded.
- Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory. Obesity. 2025;33(8):1475-1503. doi:10.1002/oby.24336 Full text.
These statements have not been evaluated by the Food and Drug Administration. Understory Nutrition products are not intended to diagnose, treat, cure, or prevent any disease. This page is general information, not medical advice. Never stop or change a prescription medication without talking to your prescriber.