Predictors of Weight Regain After Tirzepatide Discontinuation: A Post-hoc Analysis of SURMOUNT-4

Obesity is a long-lasting health condition in which the body has excess fat that can harm overall health. It affects millions of people around the world and increases the risk of diabetes (high blood sugar), heart disease, and other serious conditions. For many people, obesity is difficult to manage because the body strongly resists long-term weight loss.

Tirzepatide is a medication that helps people lose weight by acting on natural hormone pathways that helping people feel fuller, eat less, and improve how the body uses energy.

In a previous study called SURMOUNT-4, all participants first received tirzepatide during an “open-label” period, meaning everyone knew they were getting the medication. After this initial period, participants were randomly assigned to either continue tirzepatide or switch to a placebo (inactive treatment) for comparison. This design helps researchers understand whether continued treatment offers greater benefits than stopping the medication.

Many people who stop taking obesity medications regain some or all of the weight they previously lost. However, we still do not fully understand why some individuals regain more weight than others after discontinuing tirzepatide. Factors such as age, sex, starting weight, metabolism, or the amount of weight lost during treatment may all play a role, but this has not been well studied.

In this project, we will analyze information that was already collected from participants in the SURMOUNT-4 clinical trial. We will use statistical methods to compare people who regained more weight with those who maintained more of their weight loss to identify what characteristics may predict these differences. For example, we will look at data collected before treatment (such as body mass index and medical history), as well as early response to tirzepatide to see if they predict who is more likely to regain weight after stopping the medication.

By identifying predictors of weight regain, we hope to help doctors better understand who may benefit from longer-term treatment and who may need additional support if tirzepatide is discontinued. Our findings may also help guide future obesity care by supporting more personalized treatment plans for patients.