STEP 1 extension shows two-thirds of lost weight returns after stopping

Researchers who followed participants from the STEP 1 trial after the study drug was stopped report that, one year later, people had regained on average about two-thirds of the weight they had lost, and improvements in cardiometabolic measures largely went with it ^[1].

The findings come from an off-treatment extension of STEP 1, published April 19, 2022 in the journal Diabetes, Obesity and Metabolism under the title "Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension" ^[1]. The lead author is John P. H. Wilding of the University of Liverpool, and the author list includes obesity researchers from the United States, United Kingdom, Belgium, Canada and Japan, along with employees of Novo Nordisk ^[1]. The STEP 1 trial was funded by Novo Nordisk A/S ^[1].

STEP 1 tested once-weekly semaglutide 2.4 mg, the dose marketed in the United States as Wegovy, against placebo in adults with overweight or obesity, with both groups also receiving a structured lifestyle program. In this extension, both the medication and that structured lifestyle support were withdrawn at the end of the trial, and participants were followed for another year with no study treatment ^[1].

The headline result is the scale of the rebound: on average, participants had regained two-thirds of the weight they had lost during the treatment period, and the cardiometabolic improvements seen on treatment largely reversed alongside the regain ^[1]. In other words, the benefits that accumulated over the trial did not persist on their own once the drug and the program stopped.

Some details that readers may want are not in the material available here. The published summary text provided does not include the exact mean percentage of body weight lost during treatment, the exact mean regain figure, the number of participants who entered the extension, or the specific changes in blood pressure, cholesterol and blood sugar markers ^[1]. It also does not describe how individual results varied — whether some people held most of their loss while others regained all of it — or what happened to anyone who restarted a medication after the trial ended. Those questions are not answered by the information at hand.

Why it matters for patients

This extension is one of the clearest pieces of evidence that semaglutide's effect on body weight depends on continuing to take it. It supports the framing of obesity as a chronic condition, where stopping a treatment tends to be followed by a return of the condition, similar to what happens with blood pressure or cholesterol medicines when they are discontinued ^[1].

Practically, that shapes several real-world decisions US patients face. Insurance coverage for anti-obesity medications is often time-limited or can be dropped, and drug shortages and out-of-pocket costs can force interruptions. The STEP 1 extension suggests that an interruption is not neutral: the average trajectory after stopping was back toward the starting point, both for weight and for related measures like cardiometabolic risk factors ^[1].

It is also worth noting what the trial withdrew: not just the injection, but the structured lifestyle program that all participants had been receiving ^[1]. So the extension does not separate the effect of losing the drug from the effect of losing that support.

What happens next

The extension paper was first published online April 19, 2022, and appears in Volume 24, Issue 8 of Diabetes, Obesity and Metabolism, pages 1553 to 1564 ^[1]. The article is open access under a Creative Commons license and includes a plain language summary in its supporting information, so patients can read the authors' own description of the findings ^[1]. Longer-term questions — how much weight returns after two or more years off treatment, and whether restarting restores the earlier loss — are not addressed in this report.