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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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spelling 2022-12-02T19:13:48.8385347 v2 54840 2020-07-31 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 5399f4c6e6a70f3608a084ddb938511a 0000-0001-8519-4964 Steve Bain Steve Bain true false 2020-07-31 BMS 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. Journal Article Diabetes, Obesity and Metabolism 22 12 2487 2492 Wiley 1462-8902 1463-1326 body mass index, cardiovascular, liraglutide, major adverse cardiovascular events, semaglutide 1 12 2020 2020-12-01 10.1111/dom.14160 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University The LEADER and SUSTAIN 6 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT01179048 and NCT01720446). 2022-12-02T19:13:48.8385347 2020-07-31T10:06:01.4559464 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Subodh Verma 0000-0002-4018-8533 1 Darren K. McGuire 2 Steve Bain 0000-0001-8519-4964 3 Deepak L. Bhatt 4 Lawrence A. Leiter 5 C. David Mazer 6 Tea Monk Fries 7 Richard E. Pratley 8 Søren Rasmussen 9 Hrvoje Vrazic 10 Bernard Zinman 0000-0002-0041-1876 11 John B. Buse 12 54840__25994__956c25875b744dd780d3097579d0962c.pdf 54840.pdf 2022-12-02T19:12:09.7408210 Output 1079787 application/pdf Version of Record true © 2020 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License true eng http://creativecommons.org/licenses/by-nc/4.0/
title 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
spellingShingle 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
Steve Bain
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
author_id_str_mv 5399f4c6e6a70f3608a084ddb938511a
author_id_fullname_str_mv 5399f4c6e6a70f3608a084ddb938511a_***_Steve Bain
author Steve Bain
author2 Subodh Verma
Darren K. McGuire
Steve Bain
Deepak L. Bhatt
Lawrence A. Leiter
C. David Mazer
Tea Monk Fries
Richard E. Pratley
Søren Rasmussen
Hrvoje Vrazic
Bernard Zinman
John B. Buse
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container_volume 22
container_issue 12
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publishDate 2020
institution Swansea University
issn 1462-8902
1463-1326
doi_str_mv 10.1111/dom.14160
publisher Wiley
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 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.
published_date 2020-12-01T04:05:01Z
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