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

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

doi:10.1007/s13300-024-01659-7

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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

, 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

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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
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa68224

first_indexed	2024-11-25T14:21:41Z
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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.</abstract><type>Journal Article</type><journal>Diabetes Therapy</journal><volume>16</volume><journalNumber>1</journalNumber><paginationStart>15</paginationStart><paginationEnd>28</paginationEnd><publisher>Springer Science and Business Media LLC</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>1869-6953</issnPrint><issnElectronic>1869-6961</issnElectronic><keywords>Cardiovascular; Glucagon-like peptide 1 receptor agonist; Metabolic; Safety; Type 2 diabetes</keywords><publishedDay>1</publishedDay><publishedMonth>1</publishedMonth><publishedYear>2025</publishedYear><publishedDate>2025-01-01</publishedDate><doi>10.1007/s13300-024-01659-7</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>Other</apcterm><funders>SUSTAIN 6, PIONEER 6, and this post hoc analysis were funded by Novo Nordisk A/S. 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spelling	2025-02-24T13:01:31.6953305 v2 68224 2024-11-11 Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6 5399f4c6e6a70f3608a084ddb938511a 0000-0001-8519-4964 Steve Bain Steve Bain true false 2024-11-11 MEDS 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. Journal Article Diabetes Therapy 16 1 15 28 Springer Science and Business Media LLC 1869-6953 1869-6961 Cardiovascular; Glucagon-like peptide 1 receptor agonist; Metabolic; Safety; Type 2 diabetes 1 1 2025 2025-01-01 10.1007/s13300-024-01659-7 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Other 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. 2025-02-24T13:01:31.6953305 2024-11-11T11:28:26.3197099 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Steve Bain 0000-0001-8519-4964 1 Nicolas Belmar 2 Søren T. Hoff 3 Mansoor Husain 4 Søren Rasmussen 5 Tina Vilsbøll 6 Mark C. Petrie 7 68224__32904__a8c0e6df170545c18084732fd00a93b9.pdf 68224.VoR.pdf 2024-11-11T11:34:15.6462944 Output 890662 application/pdf Version of Record true © The Author(s) 2024. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. true eng http://creativecommons.org/licenses/by-nc/4.0/
title	Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6
spellingShingle	Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6 Steve Bain
title_short	Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6
title_full	Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6
title_fullStr	Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6
title_full_unstemmed	Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6
title_sort	Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6
author_id_str_mv	5399f4c6e6a70f3608a084ddb938511a
author_id_fullname_str_mv	5399f4c6e6a70f3608a084ddb938511a_***_Steve Bain
author	Steve Bain
author2	Steve Bain Nicolas Belmar Søren T. Hoff Mansoor Husain Søren Rasmussen Tina Vilsbøll Mark C. Petrie
format	Journal article
container_title	Diabetes Therapy
container_volume	16
container_issue	1
container_start_page	15
publishDate	2025
institution	Swansea University
issn	1869-6953 1869-6961
doi_str_mv	10.1007/s13300-024-01659-7
publisher	Springer Science and Business Media LLC
college_str	Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id	facultyofmedicinehealthandlifesciences
hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description	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.
published_date	2025-01-01T05:36:05Z
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Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6

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