AACE Conference Coverage

Cardiometabolic Gains Following 3 Years of Tirzepatide Treatment May Fade After Discontinuation for 17 Weeks

Anthony Calabro, MA

Key Highlights

  • 72.9% of participants experienced weight regain after discontinuing tirzepatide.
  • Participants with weight regain retained only 12.4% to 51.5% of key benefits.
  • Discontinuation of tirzepatide may compromise long-term cardiometabolic risk factor control.

After 176 weeks of tirzepatide treatment among SURMOUNT-1 participants with prediabetes, 72.9% of those who lost at least 5% of their body weight experienced weight regain following a 17-week treatment discontinuation. Researchers presented the results from their study at the American Association of Clinical Endocrinology Annual Meeting 2025 in Orlando, FL.

This post hoc analysis showed that the extent of cardiometabolic benefit retention varied markedly between those who regained weight and those who did not, with substantially greater benefit preservation observed in the latter group.

Sustained weight loss with tirzepatide is known to improve cardiometabolic risk factors in people with obesity and prediabetes. However, little is known about the trajectory of these benefits once the medication is stopped. This study was undertaken to explore whether weight regain after stopping tirzepatide is associated with a reversal in those improvements.

Researchers analyzed data from 450 tirzepatide-treated participants who had achieved ≥ 5% body weight loss at week 176. They were divided into two groups based on weight change by week 193: those with weight regain (defined as ≥ 3% body weight increase) and those without. Cardiometabolic parameters assessed included systolic blood pressure (SBP), HbA1c, fasting serum glucose (FSG), serum insulin (SI), and non–high-density lipoprotein cholesterol (non-HDL-C). The study measured benefit retention as the proportion of change from baseline maintained at week 193 versus week 176.

Among the 328 participants with weight regain, benefit retention ranged from 12.4% to 51.5% across the cardiometabolic markers, with the lowest retention observed in SBP and non-HDL-C. By contrast, among the 122 participants who maintained their weight loss, benefit retention was considerably higher, ranging from 43.9% to 131.8%, indicating not only maintenance but in some cases further improvement of SI.

“This post hoc analysis suggests that the level of improvements in CM risk factors achieved with 176 weeks of tirzepatide treatment decreased upon discontinuation for 17 weeks, which may support long-term intervention,” the study authors concluded.

Reference
Modi A. Changes in cardiometabolic risk factors upon discontinuation of tirzepatide for 17 weeks in a phase 3 three-year study. American Association of Clinical Endocrinology Annual Meeting 2025, Orlando, FL. May 15, 2025. https://aace2025.d365.events/