Effect of semaglutide versus placebo on cardiorenal outcomes by prior cardiovascular disease and baseline body mass index: Pooled post hoc analysis of SUSTAIN 6 and PIONEER 6

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Main Authors: Jingmin Zhou, Mansoor Husain, Yang Li, Wenyan Liu, Zewei Shen, Tina Vilsbøll, Junbo Ge
Format: Artículo Open Access
Published: Wiley 2025
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author Jingmin Zhou
Mansoor Husain
Yang Li
Wenyan Liu
Zewei Shen
Tina Vilsbøll
Junbo Ge
author_facet Jingmin Zhou
Mansoor Husain
Yang Li
Wenyan Liu
Zewei Shen
Tina Vilsbøll
Junbo Ge
Jingmin Zhou
Mansoor Husain
Yang Li
Wenyan Liu
Zewei Shen
Tina Vilsbøll
Junbo Ge
collection Wiley Open Access
contents Effect of semaglutide versus placebo on cardiorenal outcomes by prior cardiovascular disease and baseline body mass index: Pooled post hoc analysis of SUSTAIN 6 and PIONEER 6 Jingmin Zhou Mansoor Husain Yang Li Wenyan Liu Zewei Shen Tina Vilsbøll Junbo Ge Diabetes, Obesity and Metabolism Abstract Aims Cardiorenal effects of semaglutide in people with type 2 diabetes (T2D) at high cardiovascular (CV) risk were investigated. Materials and Methods Post hoc analyses of pooled SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716) data assessed time to primary major adverse CV events (MACE; CV death, non‐fatal myocardial infarction, or non‐fatal stroke), expanded MACE (MACE + hospitalisation for unstable angina or heart failure), CV death, all‐cause death, and new or worsening nephropathy. The impact of body weight (BW) changes on primary MACE risk was also evaluated. Participants were stratified by prior CV disease (CVD) status and baseline body mass index (BMI). Results Semaglutide significantly reduced the risk of primary and expanded MACE, with a nonsignificant risk reduction of CV and all‐cause death versus placebo in the overall population; the effect was consistent across all subgroups ( p INT  >0.05 for all comparisons). Semaglutide consistently reduced nephropathy risk versus placebo in the SUSTAIN 6 population (HR [95% CI]: 0.64 [0.46; 0.88], p  = 0.0054) and across all subgroups ( p INT  >0.05 for all comparisons). When accounting for BW changes, treatment effects on primary MACE risk in the overall population and by BMI subgroups remained similar compared with the results of the main analysis. Conclusions Semaglutide treatment improved cardiorenal outcomes versus placebo in people with T2D, regardless of prior CVD and baseline BMI. This improvement was observed even when accounting for changes in BW, indicating direct effects of semaglutide on the cardiorenal system. This analysis supports the broad efficacy of semaglutide in a diverse T2D population. 10.1111/dom.16621 http://creativecommons.org/licenses/by-nc-nd/4.0/
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spellingShingle Effect of semaglutide versus placebo on cardiorenal outcomes by prior cardiovascular disease and baseline body mass index: Pooled post hoc analysis of SUSTAIN 6 and PIONEER 6
Jingmin Zhou
Mansoor Husain
Yang Li
Wenyan Liu
Zewei Shen
Tina Vilsbøll
Junbo Ge
Diabetes, Obesity and Metabolism
Effect of semaglutide versus placebo on cardiorenal outcomes by prior cardiovascular disease and baseline body mass index: Pooled post hoc analysis of SUSTAIN 6 and PIONEER 6 Jingmin Zhou Mansoor Husain Yang Li Wenyan Liu Zewei Shen Tina Vilsbøll Junbo Ge Diabetes, Obesity and Metabolism Abstract Aims Cardiorenal effects of semaglutide in people with type 2 diabetes (T2D) at high cardiovascular (CV) risk were investigated. Materials and Methods Post hoc analyses of pooled SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716) data assessed time to primary major adverse CV events (MACE; CV death, non‐fatal myocardial infarction, or non‐fatal stroke), expanded MACE (MACE + hospitalisation for unstable angina or heart failure), CV death, all‐cause death, and new or worsening nephropathy. The impact of body weight (BW) changes on primary MACE risk was also evaluated. Participants were stratified by prior CV disease (CVD) status and baseline body mass index (BMI). Results Semaglutide significantly reduced the risk of primary and expanded MACE, with a nonsignificant risk reduction of CV and all‐cause death versus placebo in the overall population; the effect was consistent across all subgroups ( p INT  >0.05 for all comparisons). Semaglutide consistently reduced nephropathy risk versus placebo in the SUSTAIN 6 population (HR [95% CI]: 0.64 [0.46; 0.88], p  = 0.0054) and across all subgroups ( p INT  >0.05 for all comparisons). When accounting for BW changes, treatment effects on primary MACE risk in the overall population and by BMI subgroups remained similar compared with the results of the main analysis. Conclusions Semaglutide treatment improved cardiorenal outcomes versus placebo in people with T2D, regardless of prior CVD and baseline BMI. This improvement was observed even when accounting for changes in BW, indicating direct effects of semaglutide on the cardiorenal system. This analysis supports the broad efficacy of semaglutide in a diverse T2D population. 10.1111/dom.16621 http://creativecommons.org/licenses/by-nc-nd/4.0/
title Effect of semaglutide versus placebo on cardiorenal outcomes by prior cardiovascular disease and baseline body mass index: Pooled post hoc analysis of SUSTAIN 6 and PIONEER 6
topic Diabetes, Obesity and Metabolism
url https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.16621