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Once-Weekly Semaglutide in Adults with Overweight or Obesity

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journal contribution
posted on 27.05.2021, 11:05 by John PH Wilding, Rachel L Batterham, Salvatore Calanna, Melanie Davies, Luc F Van Gaal, Ildiko Lingvay, Barbara M McGowan, Julio Rosenstock, Marie TD Tran, Thomas A Wadden, Sean Wharton, Koutaro Yokote, Niels Zeuthen, Robert F Kushner
BACKGROUND
Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.

METHODS
In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.

RESULTS
The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo, for an estimated treatment difference of −12.4 percentage points (95% confidence interval [CI], −13.4 to −11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was −15.3 kg in the semaglutide group as compared with −2.6 kg in the placebo group (estimated treatment difference, −12.7 kg; 95% CI, −13.7 to −11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]).

CONCLUSIONS
In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935. opens in new tab).

Funding

Novo Nordisk

History

Citation

N Engl J Med 2021; 384:989-1002 DOI: 10.1056/NEJMoa2032183

Author affiliation

Diabetes Research Centre, College of Life Sciences

Version

VoR (Version of Record)

Published in

New England Journal of Medicine

Volume

384

Issue

11

Pagination

989 - 1002

Publisher

Massachusetts Medical Society

issn

0028-4793

eissn

1533-4406

Copyright date

2021

Available date

18/09/2021

Spatial coverage

United States

Language

English