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Efficacy and Safety of Semaglutide 2.4 MG Once-Weekly in Adults With Overweight or Obesity and Type 2 Diabetes (STEP 2)

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posted on 2021-12-06, 10:38 authored by Melanie Davies, Louise Færch, Ole K Jeppesen, Arash Pakseresht, Sue D Pedersen, Leigh Perreault, Julio Rosenstock, Iichiro Shimomura, Adie Viljoen, Thomas A Wadden, Ildiko Lingvay
Background: In people with overweight/obesity and type 2 diabetes (T2D), achievement of weight loss can be a challenge. STEP 2 investigated the efficacy and safety of semaglutide 2.4 mg for weight management in adults with overweight/obesity and T2D.

Methods: This randomized, double-blind, double-dummy, placebo-controlled, phase 3 trial was conducted at 149 sites across 12 countries (NCT03552757). Adults aged ≥18 years with body mass index (BMI) ≥27 kg/m2, T2D, HbA1c between 7–10% (53–86 mmol/mol), and receiving ≤3 oral glucose-lowering agents were randomized 1:1:1 to once-weekly subcutaneous (s.c.) semaglutide 2.4 mg or 1.0 mg, or placebo, as adjunct to a reduced-calorie diet and increased physical activity for 68 weeks. The co-primary endpoints were percentage change in body weight and proportion of participants achieving weight loss ≥5% for semaglutide 2.4 mg vs placebo. Cardiovascular risk factors, glycemia and safety/tolerability were also assessed. Two estimands were defined: treatment policy and trial product; results are presented for the treatment policy estimand, unless stated otherwise.

Results: 1,210 participants (mean: age 55 years, body weight 99.8 kg, BMI 35.7 kg/m2, HbA1c 8.1%, diabetes duration 8.0 years; 50.9% female) were randomized. Mean body weight change from baseline to week 68 was −9.6% with semaglutide 2.4 mg vs −3.4% with placebo (estimated treatment difference [ETD]: −6.2%; 95% confidence interval [CI]: −7.3, −5.2; p<0.0001) and −7.0% for semaglutide 1.0 mg (ETD for semaglutide 2.4 mg vs 1.0 mg: −2.7%; 95% CI: −3.7, −1.6; p<0.0001). Similar results were obtained with the trial product estimand: mean body weight change −10.6% for semaglutide 2.4 mg vs −3.1% for placebo (ETD: −7.6%; 95% CI: −8.6, −6.6; p<0.0001) and 7.6% for semaglutide 1.0 mg (ETD vs semaglutide 2.4 mg: −3.1%; 95% CI: −4.1, −2.1; p<0.0001). Participants on semaglutide 2.4 mg were more likely to achieve weight loss ≥5%, ≥10%, ≥15% and ≥20% vs placebo (68.8% vs 28.5%, 45.6% vs 8.2%, 25.8% vs 3.2% and 13.1% vs 1.6%, respectively; p value for odds ratios <0.0001 for all). Mean change in HbA1c from baseline to week 68 was −1.6% for semaglutide 2.4 mg vs −0.4% for placebo (p<0.0001). Greater improvements with semaglutide 2.4 mg vs placebo were also seen in waist circumference, BMI, systolic blood pressure, fasting plasma glucose, C-reactive protein, and lipids (HDL, VLDL, free fatty acids, and triglycerides) (p<0.05 for all). The most frequent adverse events were gastrointestinal disorders (typically transient and mild-to-moderate), occurring in 57.5%, 63.5% and 34.3% of participants receiving semaglutide 1.0 mg, 2.4 mg and placebo, respectively.

Conclusion: Semaglutide 2.4 mg, as adjunct to lifestyle intervention, was efficacious and well tolerated for weight management in adults with overweight or obesity and T2D, providing significantly greater weight loss vs placebo and semaglutide 1.0 mg at week 68.

History

Citation

Journal of the Endocrine Society, Volume 5, Issue Supplement_1, April-May 2021, Pages A10–A11, https://doi.org/10.1210/jendso/bvab048.019

Author affiliation

Diabetes Research Centre, College of Life Sciences

Source

ENDO 2021

Version

  • VoR (Version of Record)

Published in

Journal of the Endocrine Society

Volume

5

Issue

Suppl 1

Pagination

A10 - A11

Publisher

Endocrine Society

issn

2472-1972

eissn

2472-1972

Copyright date

2021

Available date

2021-12-06

Spatial coverage

Online

Temporal coverage: start date

2021-04-01

Temporal coverage: end date

2021-05-01

Language

en

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