Cardiometabolic risk factors efficacy of semaglutide in the STEP program

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ABSTRACT

People with overweight or obesity often suffer from associated cardiometabolic diseases and comorbidities. Current therapies for obesity include lifestyle intervention, bariatric surgery, and pharmacotherapy. The magnitude of weight loss achieved with these therapies can determine the level of improvement in various comorbidities. Once-weekly subcutaneous semaglutide 2.4 mg is a glucagon-like peptide-1 receptor agonist recently approved by the US Food and Drug Administration for the treatment of obesity. This article reviews data from the global phase 3 Semaglutide Treatment Effect in People with obesity (STEP) program, comparing the efficacy of once-weekly subcutaneous semaglutide 2.4 mg versus placebo for weight loss and improvements in cardiometabolic parameters across the STEP 1 to 5 trials. In STEP 1 to 3 and STEP 5, semaglutide led to greater reductions from baseline versus placebo in body weight, waist circumference, body mass index, systolic blood pressure (SBP), and diastolic blood pressure, as well as positive changes in glycated hemoglobin (HbA_1c), C-reactive protein, and lipid levels. In STEP 4, all participants had a 20-week run-in period on semaglutide before either continuing on semaglutide or switching to placebo at week 20 in a 2:1 ratio for 48 weeks. At week 68, continued semaglutide led to further reductions from week 20 in HbA_1c, improvements in lipid profile, and stabilization of SBP. Overall, across the STEP trials, treatment with semaglutide 2.4 mg versus placebo improved cardiometabolic risk factors associated with obesity, illustrating an effective treatment option for people with overweight (and associated comorbidities) or obesity.

KEYWORDS:

• Semaglutide 2.4 mg
• obesity
• overweight
• weight loss
• cardiometabolic parameters
• anti-obesity medication

Acknowledgments

Medical writing and editorial support were provided by Casey McKeown of Axis, a division of Spirit Medical Communications Group Limited (and were funded by Novo Nordisk Inc.), under the direction of the authors. Novo Nordisk Inc. also performed a medical accuracy review.

Declaration of financial/other relationships

Anastassia Amaro: advisory boards and consultant – Medality Medical, Novo Nordisk, and Pfizer, and research support – Altimmune, Eli Lilly, Fractyl Health, and Novo Nordisk.

Neil S. Skolnik: advisory boards and consultant – Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Genetech, GSK, Sanofi, Sanofi Pasteur, and Teva; speaker – AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, and GSK; and research support – AstraZeneca, Bayer, Boehringer Ingelheim, GSK, and Sanofi.

Danny Sugimoto: research grants – AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Merck, and Novo Nordisk.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This peer-reviewed article was supported by Novo Nordisk Inc.; the company was provided with the opportunity to perform a medical accuracy review.