Research brief · 2026-09-09
What Happens to Blood Sugar After Stopping a GLP-1?
Semaglutide and tirzepatide are prescription medications that lower blood sugar and body weight for as long as they are taken. What happens to blood sugar when they are stopped is a question with real stakes, and the most direct evidence comes from a post hoc analysis of the SURMOUNT-4 tirzepatide trial.
SURMOUNT-4 gave participants tirzepatide openly for 36 weeks, during which they lost 20.9 percent of body weight on average, then randomised 670 of them to continue or switch to placebo for another 52 weeks. A 2026 analysis by Horn and colleagues in JAMA Internal Medicine took the placebo-switched group and sorted them by how much of their lost weight came back: under a quarter, a quarter to half, half to three-quarters, or three-quarters or more. HbA1c rose in step with regain, from 0.14 percentage points in the lowest-regain group to 0.35 points in the highest, a statistically significant trend. Systolic blood pressure rose from 6.8 to 10.4 millimetres of mercury across the same categories, and waist circumference was unchanged in the low-regain group but up 14.7 centimetres in the high-regain group. Fasting insulin swung most of all. People who kept off at least three-quarters of their lost weight showed no significant change in waist, non-HDL cholesterol or fasting insulin.
A 2026 review by Shah and colleagues in Diabetes, Obesity and Metabolism pulled together the randomised withdrawal trials, including the STEP 1 extension and SURMOUNT-4, with observational cohorts totalling more than 289,000 patients. Its modelling estimate was that glycaemic, blood pressure and lipid markers drift back toward pre-treatment baseline within about twelve months of stopping, with HbA1c normalising over twelve to eighteen months. The same review flagged an association between early discontinuation and higher risk of coronary disease and heart failure compared with staying on therapy.
The semaglutide data tell the same story with a caveat. In the STEP 1 extension, published by Wilding and colleagues in 2022, cardiometabolic improvements moved back toward baseline over the year after stopping, in parallel with the two-thirds of lost weight that returned. But STEP 1 enrolled people without diabetes, so its glucose findings describe metabolically healthier people.
That is the detail that is easy to miss. SURMOUNT-4 also excluded people with type 2 diabetes. The two largest, best-controlled withdrawal trials were therefore conducted in people who were not diabetic to begin with. Their HbA1c changes are real, but they describe movement within a largely non-diabetic range, not a diabetic patient's control unravelling. No trial has tested tapering versus abrupt stopping, follow-up ends around a year, and nothing is published on whether restarting works as well the second time. Anyone managing diabetes should talk to their physician before changing anything.
Sources
- Horn DB, et al. Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial
- JAMA Internal Medicine 2026
- Shah E, et al. Clinical Management of Weight Regain and Cardiometabolic Consequences After Discontinuation of GLP-1 Receptor Agonists
- Diabetes, Obesity & Metabolism 2026
- Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension
- Diabetes, Obesity & Metabolism 2022
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