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Effects of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across body mass index categories in type 2 diabetes: Results of the LEADER and SUSTAIN 6 trials

Subodh Verma Orcid Logo, Darren K. McGuire, Steve Bain Orcid Logo, Deepak L. Bhatt, Lawrence A. Leiter, C. David Mazer, Tea Monk Fries, Richard E. Pratley, Søren Rasmussen, Hrvoje Vrazic, Bernard Zinman Orcid Logo, John B. Buse

Diabetes, Obesity and Metabolism, Volume: 22, Issue: 12, Pages: 2487 - 2492

Swansea University Author: Steve Bain Orcid Logo

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DOI (Published version): 10.1111/dom.14160

Abstract

Associations between body mass index (BMI) and the cardiovascular (CV) and kidney efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) are uncertain; therefore, data analysed separately from the Liraglutide Effect and Action in Diabetes: Evaluation...

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Published in: Diabetes, Obesity and Metabolism
ISSN: 1462-8902 1463-1326
Published: Wiley 2020
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URI: https://cronfa.swan.ac.uk/Record/cronfa54840
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Abstract: Associations between body mass index (BMI) and the cardiovascular (CV) and kidney efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) are uncertain; therefore, data analysed separately from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN 6) were examined. These international, randomized, placebo-controlled trials investigated liraglutide and semaglutide (both subcutaneous) in patients with T2D and at high risk of CV events. In post hoc analyses, patients were categorized by baseline BMI (<25, ≥25-<30, ≥30-<35 and ≥35 kg/m2), and CV and kidney outcomes with GLP-1 RA versus placebo were analysed. All baseline BMI data from LEADER (n = 9331) and SUSTAIN 6 (n = 3290) were included (91% and 92% of patients with overweight or obesity, respectively). In SUSTAIN 6, nominally significant heterogeneity of semaglutide efficacy by baseline BMI was observed for CV death/myocardial infarction/stroke (major adverse CV events, primary outcome of both; Pinteraction = .02); otherwise, there was no statistical heterogeneity for either GLP-1 RA versus placebo across BMI categories for key CV and kidney outcomes. The lack of statistical heterogeneity from these cardiorenal outcomes implies that liraglutide and semaglutide may be beneficial for many patients and is probable not to depend on their baseline BMI, but further study is needed.
Keywords: body mass index, cardiovascular, liraglutide, major adverse cardiovascular events, semaglutide
College: Swansea University Medical School
Funders: The LEADER and SUSTAIN 6 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT01179048 and NCT01720446).
Issue: 12
Start Page: 2487
End Page: 2492