Waist size and blood pressure tracked weight regain after tirzepatide stopped, SURMOUNT-4 analysis finds

An analysis of the SURMOUNT-4 trial published in JAMA Internal Medicine reports that after adults with obesity stopped taking tirzepatide, their waistlines and blood pressure moved in step with how much weight they regained — the more weight came back, the more those measurements worsened ^[1][2].

The paper is a post hoc analysis, which means researchers went back to data from a completed trial and sorted participants into groups after the fact ^[1]. SURMOUNT-4 itself was a withdrawal study. Everyone took tirzepatide (sold as Zepbound for obesity and Mounjaro for type 2 diabetes) during a 36-week lead-in period. Participants who lost at least 10% of their body weight by week 36 were then randomly assigned either to keep taking tirzepatide or to stop it, and were followed to week 88 ^[1]. The new analysis divided the people who stopped the drug into categories based on how much of their lost weight returned ^[1].

Waist circumference increased by 0.8 centimeters in the category that regained the least weight and by 14.7 centimeters in the category that regained the most ^[1]. Across the same range of weight regain, systolic blood pressure rose by 6.8 to 10.4 mm Hg ^[1]. The trial's figures report that differences among the regain categories were statistically significant for weight, body mass index and waist circumference, and for both systolic and diastolic blood pressure ^[1].

The paper also reports changes in blood sugar measures by regain category, and lists fasting lipids along with measures of insulin resistance and beta-cell function (HOMA2-IR and HOMA2-B) among its supplemental results ^[1].

Several of the paper's authors list affiliations with Eli Lilly and Company, the maker of tirzepatide, including its Indianapolis headquarters and Lilly offices in France and Portugal ^[1]. JAMA Internal Medicine also published an editorial titled "Lessons Learned From Antiobesity Medication Withdrawal Trials" and a comment and response titled "Understanding Weight Regain After Tirzepatide Withdrawal" ^[1].

Why it matters for patients

People stop GLP-1 medications for many reasons, including cost, side effects and supply problems, and regain after stopping is common. The pattern described in this analysis suggests that health measures such as blood pressure and waist size follow body weight rather than any lasting effect of having taken the drug ^[1]. Participants who kept more of their weight loss also kept more of the improvement in those measures, while those who regained the most saw the measures move back toward their starting points ^[1]. In practical terms, the analysis found that partial regain preserved partial benefit — benefit that was not somehow "banked" by the drug itself.

There are limits to what this type of analysis can show. The regain categories were formed after the trial ended, not assigned at random, so the analysis cannot prove that regaining weight caused the changes in blood pressure or waist size, or that some other factor separated the groups. The measures reported are intermediate markers, not heart attacks, strokes or deaths; whether these differences translate into cardiovascular events has not been reported here.

What happens next

The paper appears with an accompanying editorial and a comment and response in the same journal ^[1]. No new randomized trial comparing strategies for tapering or stopping tirzepatide is described in these publications, and no date has been announced for one. The withdrawal phase of SURMOUNT-4 ran to week 88, and the analysis covers that period ^[1]. Details such as the number of participants in each regain category and how the category cutoffs were defined are not laid out in the figures and tables cited here ^[1].