STEP 1 extension finds two-thirds of lost weight returns a year after stopping semaglutide

People who stopped taking semaglutide 2.4 mg and a structured lifestyle program regained on average about two-thirds of the weight they had lost within a year, and the heart and metabolic improvements that came with the weight loss largely reversed, according to the STEP 1 trial extension published in Diabetes, Obesity and Metabolism ^[1].

The report describes what happened after treatment ended in STEP 1. In the extension, both the drug and the lifestyle program were withdrawn, and participants were followed for one year ^[1]. By the end of that year, the average participant had regained roughly two-thirds of the weight lost during treatment ^[1]. The paper also reports that cardiometabolic gains — the changes in blood pressure, blood sugar, cholesterol and similar measures that accompanied the weight loss — were largely reversed as the weight returned ^[1].

The extension was published online on April 19, 2022, in volume 24, issue 8 of the journal, pages 1553 to 1564, and is open access ^[1]. Authors include researchers from the University of Liverpool, University College London, the University of Leicester, the University of Pennsylvania, the University of Texas Southwestern Medical Center and other academic centers, along with three authors employed by Novo Nordisk A/S ^[1]. The STEP 1 trial was funded by Novo Nordisk A/S, the company that developed semaglutide ^[1].

How much weight individual participants regained, how many returned to their starting weight, and whether the regain leveled off after the one-year follow-up are not reported in the extension ^[1]. Because the drug and the lifestyle program were stopped at the same time, the report also does not separate how much of the regain is tied to ending the medication and how much to ending the program; that breakdown has not been reported ^[1].

Why it matters for patients

Weight regain after stopping is the central practical question for anyone weighing whether to start a GLP-1 medication for weight management, and the STEP 1 extension is one of the clearest looks at it. In this trial, the average participant did not hold onto most of the weight lost once both the drug and the program stopped ^[1].

The reversal of cardiometabolic measures matters too. Those changes — in blood pressure, blood sugar and cholesterol-related measures — were part of what made the weight loss medically meaningful, and they moved back toward where they started as weight returned ^[1].

What the extension does not answer is what happens with different stopping patterns, such as tapering rather than stopping outright, or continuing a lifestyle program after the drug ends. It also does not address cost, insurance coverage or side effects, which are often part of the decision for US patients. Those questions have not been answered by this paper ^[1].

The findings describe averages across trial participants who were treated and then withdrew from treatment. They are not a prediction of what will happen to any single person, and the extension does not report how many participants avoided regain altogether ^[1].