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Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6

Steve Bain Orcid Logo, Nicolas Belmar, Søren T. Hoff, Mansoor Husain, Søren Rasmussen, Tina Vilsbøll, Mark C. Petrie

Diabetes Therapy, Volume: 16, Issue: 1, Pages: 15 - 28

Swansea University Author: Steve Bain Orcid Logo

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DOI (Published version): 10.1007/s13300-024-01659-7

Abstract

Introduction: The high risk of cardiovascular events in people with type 2 diabetes increases with age. The cardiovascular effects of once-weekly subcutaneous and once-daily oral semaglutide versus placebo in people with type 2 diabetes at high cardiovascular risk were investigated in the SUSTAIN 6...

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Published in: Diabetes Therapy
ISSN: 1869-6953 1869-6961
Published: Springer Science and Business Media LLC 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa68224
Abstract: Introduction: The high risk of cardiovascular events in people with type 2 diabetes increases with age. The cardiovascular effects of once-weekly subcutaneous and once-daily oral semaglutide versus placebo in people with type 2 diabetes at high cardiovascular risk were investigated in the SUSTAIN 6 and PIONEER 6 cardiovascular outcomes trials, respectively. It is unknown whether the effects of semaglutide are age dependent. Methods: This post hoc analysis evaluated cardiovascular, metabolic, and safety outcomes with semaglutide versus placebo in age subgroups (≤ 60; > 60 to ≤ 65; > 65 to ≤ 70; and > 70 years) pooled from SUSTAIN 6 and PIONEER 6. Major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), changes from baseline in glycated hemoglobin A1c (HbA1c) and body weight, and adverse events were analyzed. Results: Semaglutide reduced major adverse cardiovascular events and its components versus placebo across age subgroups (most hazard ratios < 1.0; pinteraction > 0.05). The treatment difference in HbA1c reduction was greater in those aged ≤ 60 years than in older subgroups (pinteraction = 0.01). Reductions in body weight with semaglutide versus placebo were consistent across age subgroups (pinteraction = 0.124). Serious adverse events or severe hypoglycemic episodes did not differ between semaglutide and placebo across age subgroups. Conclusion: Semaglutide consistently reduced major adverse cardiovascular events and body weight versus placebo across age subgroups; its safety profile did not differ with age. These results suggest that relaxing HbA1c targets based solely on age may not always be required for people with type 2 diabetes.
Keywords: Cardiovascular; Glucagon-like peptide 1 receptor agonist; Metabolic; Safety; Type 2 diabetes
College: Faculty of Medicine, Health and Life Sciences
Funders: SUSTAIN 6, PIONEER 6, and this post hoc analysis were funded by Novo Nordisk A/S. The sponsor designed the studies; funded the data collection, analysis, and interpretation; and was responsible for site monitoring, the writing of this report, and the decision to submit for publication. The journal’s Rapid Service Fee was funded by Novo Nordisk A/S.
Issue: 1
Start Page: 15
End Page: 28

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