Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6

Husain, Mansoor; Consoli, Agostino; Remigis, Alessandra De; Pettersson, Anna Sina; Rasmussen, Søren; Bain, Steve

doi:10.1186/s12933-022-01489-6

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Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6

Mansoor Husain, Agostino Consoli, Alessandra De Remigis, Anna Sina Pettersson Meyer, Søren Rasmussen, Steve Bain

Cardiovascular Diabetology, Volume: 21, Issue: 1

Swansea University Author: Steve Bain

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DOI (Published version): 10.1186/s12933-022-01489-6

Abstract

BackgroundCardiovascular outcome trials (CVOTs) are conducted on a background of standard of care including metformin. These analyses sought to determine whether the cardiovascular (CV) effects of semaglutide and other glucagon-like peptide-1 receptor agonists (GLP-1RAs) vary according to baseline m...

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Published in:	Cardiovascular Diabetology
ISSN:	1475-2840
Published:	Springer Science and Business Media LLC 2022
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URI:	https://cronfa.swan.ac.uk/Record/cronfa59680
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first_indexed	2022-03-21T17:09:22Z
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spelling	v2 59680 2022-03-21 Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6 5399f4c6e6a70f3608a084ddb938511a 0000-0001-8519-4964 Steve Bain Steve Bain true false 2022-03-21 BMS BackgroundCardiovascular outcome trials (CVOTs) are conducted on a background of standard of care including metformin. These analyses sought to determine whether the cardiovascular (CV) effects of semaglutide and other glucagon-like peptide-1 receptor agonists (GLP-1RAs) vary according to baseline metformin use.MethodsA post hoc analysis was conducted using pooled SUSTAIN 6 and PIONEER 6 CVOT data in subjects with and without metformin use at baseline. Additionally, a trial-level meta-analysis was conducted using data from seven CVOTs with GLP-1RAs–SUSTAIN 6, PIONEER 6, HARMONY OUTCOMES, LEADER, REWIND, EXSCEL and AMPLITUDE-O–including adults with type 2 diabetes at high CV risk, and a primary endpoint of time to first major adverse CV event (MACE).ResultsIn the post hoc analysis, the no-metformin subgroup was older, with a higher body mass index, lower estimated glomerular filtration rate and higher CV risk at baseline vs the metformin subgroup. Hazard ratios (95% confidence intervals) for the reduction in risk of MACE with semaglutide vs placebo in the metformin and no-metformin subgroups were 0.70 (0.55;0.89) and 0.86 (0.60;1.22), respectively. No significant interaction between the treatment effect on MACE and metformin subgroup was observed. Findings for other CV endpoints were similar. In the meta-analysis, treatment effect (GLP-1RA vs placebo) on CV outcomes was no different with vs without baseline metformin (overall ratio between the hazard ratios for metformin vs no-metformin 1.09 [0.96;1.22]).ConclusionThese findings indicate that the CV outcomes for semaglutide were similar regardless of baseline metformin use, which may also apply to all GLP-1RAs. Journal Article Cardiovascular Diabetology 21 1 Springer Science and Business Media LLC 1475-2840 Semaglutide, SUSTAIN 6, PIONEER 6, Major adverse cardiovascular event, Cardiovascular outcome trial, Metformin 28 4 2022 2022-04-28 10.1186/s12933-022-01489-6 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University SUSTAIN 6, PIONEER 6, and the post hoc and meta-analyses presented in this manuscript were funded by Novo Nordisk A/S. 2024-02-02T08:27:22.8786944 2022-03-21T17:04:55.7738463 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Mansoor Husain 1 Agostino Consoli 2 Alessandra De Remigis 3 Anna Sina Pettersson Meyer 4 Søren Rasmussen 5 Steve Bain 0000-0001-8519-4964 6 59680__24112__9592909acf0149ebb7555a21bf71f42b.pdf 59680.pdf 2022-05-17T15:35:16.3555111 Output 1185814 application/pdf Version of Record true © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License true eng http://creativecommons.org/licenses/by/4.0/
title	Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6
spellingShingle	Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6 Steve Bain
title_short	Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6
title_full	Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6
title_fullStr	Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6
title_full_unstemmed	Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6
title_sort	Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6
author_id_str_mv	5399f4c6e6a70f3608a084ddb938511a
author_id_fullname_str_mv	5399f4c6e6a70f3608a084ddb938511a_***_Steve Bain
author	Steve Bain
author2	Mansoor Husain Agostino Consoli Alessandra De Remigis Anna Sina Pettersson Meyer Søren Rasmussen Steve Bain
format	Journal article
container_title	Cardiovascular Diabetology
container_volume	21
container_issue	1
publishDate	2022
institution	Swansea University
issn	1475-2840
doi_str_mv	10.1186/s12933-022-01489-6
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
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hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description	BackgroundCardiovascular outcome trials (CVOTs) are conducted on a background of standard of care including metformin. These analyses sought to determine whether the cardiovascular (CV) effects of semaglutide and other glucagon-like peptide-1 receptor agonists (GLP-1RAs) vary according to baseline metformin use.MethodsA post hoc analysis was conducted using pooled SUSTAIN 6 and PIONEER 6 CVOT data in subjects with and without metformin use at baseline. Additionally, a trial-level meta-analysis was conducted using data from seven CVOTs with GLP-1RAs–SUSTAIN 6, PIONEER 6, HARMONY OUTCOMES, LEADER, REWIND, EXSCEL and AMPLITUDE-O–including adults with type 2 diabetes at high CV risk, and a primary endpoint of time to first major adverse CV event (MACE).ResultsIn the post hoc analysis, the no-metformin subgroup was older, with a higher body mass index, lower estimated glomerular filtration rate and higher CV risk at baseline vs the metformin subgroup. Hazard ratios (95% confidence intervals) for the reduction in risk of MACE with semaglutide vs placebo in the metformin and no-metformin subgroups were 0.70 (0.55;0.89) and 0.86 (0.60;1.22), respectively. No significant interaction between the treatment effect on MACE and metformin subgroup was observed. Findings for other CV endpoints were similar. In the meta-analysis, treatment effect (GLP-1RA vs placebo) on CV outcomes was no different with vs without baseline metformin (overall ratio between the hazard ratios for metformin vs no-metformin 1.09 [0.96;1.22]).ConclusionThese findings indicate that the CV outcomes for semaglutide were similar regardless of baseline metformin use, which may also apply to all GLP-1RAs.
published_date	2022-04-28T08:27:22Z
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Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6

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