TY - JOUR
T1 - Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk
AU - Husain, Mansoor
AU - Bain, Stephen C.
AU - Jeppesen, Ole K.
AU - Lingvay, Ildiko
AU - Sørrig, Rasmus
AU - Treppendahl, Marianne B.
AU - Vilsbøll, Tina
N1 - Funding Information:
information These studies were funded by Novo Nordisk A/S, Denmark.We thank all the patients, investigators and trial-site staff members who were involved in the conduct of these trials; Thomas Hansen and Signe Harring (Novo Nordisk) for review and suggestions for revising the manuscript; and Ellen Robertshaw, PhD, at AXON Communications (funded by Novo Nordisk) for medical writing and editorial assistance. These studies were funded by Novo Nordisk A/S, Denmark.
Publisher Copyright:
© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Aim: To investigate the effects of semaglutide versus comparators on major adverse cardiovascular events (MACE: cardiovascular [CV] death, nonfatal myocardial infarction [MI] and nonfatal stroke) and hospitalization for heart failure (HF) in the SUSTAIN (subcutaneous semaglutide) and PIONEER (oral semaglutide) trials across subgroups of varying CV risk. Methods: Post hoc analyses of individual patient-level data combined from SUSTAIN 6 and PIONEER 6 were performed to assess MACE and HF. MACE were analysed in subjects with and without: established CV disease and/or chronic kidney disease; prior MI or stroke; and prior HF. MACE in the SUSTAIN and PIONEER glycaemic efficacy trials were also assessed. Results: In SUSTAIN 6 and PIONEER 6 combined, the hazard ratio (HR) for effect of semaglutide versus placebo on overall MACE was 0.76 (95% CI 0.62, 0.92), which was mainly driven by the effect on nonfatal stroke (HR 0.65 [95% CI 0.43, 0.97]). The HR for hospitalization for HF was 1.03 (95% CI 0.75, 1.40). The HRs for MACE were <1.0 in all subgroups, except for those with prior HF (HR 1.06 [95% CI 0.72, 1.57]); P-values for interaction of subgroup on treatment effect were >0.05, except for HF (0.046). In the combined glycaemic efficacy trials, the HR for effect of semaglutide versus comparators on MACE was 0.85 (95% CI 0.55, 1.33). Conclusions: In SUSTAIN and PIONEER combined, glucagon-like peptide-1 analogue semaglutide showed consistent effects on MACE versus comparators across varying CV risk. No effect of semaglutide on MACE was observed in subjects with prior HF.
AB - Aim: To investigate the effects of semaglutide versus comparators on major adverse cardiovascular events (MACE: cardiovascular [CV] death, nonfatal myocardial infarction [MI] and nonfatal stroke) and hospitalization for heart failure (HF) in the SUSTAIN (subcutaneous semaglutide) and PIONEER (oral semaglutide) trials across subgroups of varying CV risk. Methods: Post hoc analyses of individual patient-level data combined from SUSTAIN 6 and PIONEER 6 were performed to assess MACE and HF. MACE were analysed in subjects with and without: established CV disease and/or chronic kidney disease; prior MI or stroke; and prior HF. MACE in the SUSTAIN and PIONEER glycaemic efficacy trials were also assessed. Results: In SUSTAIN 6 and PIONEER 6 combined, the hazard ratio (HR) for effect of semaglutide versus placebo on overall MACE was 0.76 (95% CI 0.62, 0.92), which was mainly driven by the effect on nonfatal stroke (HR 0.65 [95% CI 0.43, 0.97]). The HR for hospitalization for HF was 1.03 (95% CI 0.75, 1.40). The HRs for MACE were <1.0 in all subgroups, except for those with prior HF (HR 1.06 [95% CI 0.72, 1.57]); P-values for interaction of subgroup on treatment effect were >0.05, except for HF (0.046). In the combined glycaemic efficacy trials, the HR for effect of semaglutide versus comparators on MACE was 0.85 (95% CI 0.55, 1.33). Conclusions: In SUSTAIN and PIONEER combined, glucagon-like peptide-1 analogue semaglutide showed consistent effects on MACE versus comparators across varying CV risk. No effect of semaglutide on MACE was observed in subjects with prior HF.
KW - cardiovascular disease
KW - clinical trial
KW - glucagon-like peptide-1 analogue
KW - phase III study
KW - type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85079040630&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079040630&partnerID=8YFLogxK
U2 - 10.1111/dom.13955
DO - 10.1111/dom.13955
M3 - Article
C2 - 31903692
AN - SCOPUS:85079040630
SN - 1462-8902
VL - 22
SP - 442
EP - 451
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 3
ER -