Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes: Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6
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Background: GLP-1 RA (glucagon-like peptide-1 receptor agonists), including semaglutide, may reduce stroke risk in people with type 2 diabetes. This post hoc analysis examined the subcutaneous and oral semaglutide effects, versus placebo, on stroke and its subtypes in people with type 2 diabetes at high cardiovascular risk. Methods: SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and PIONEER 6 (Peptide Innovation for Early Diabetes Treatment) were randomized cardiovascular outcome trials of subcutaneous and oral semaglutide in people with type 2 diabetes at high cardiovascular risk, respectively. Time to first stroke and stroke subtypes were analyzed using a Cox proportional hazards model stratified by trial with pooled treatment as a factor. The impact of prior stroke, prior myocardial infarction or stroke, age, sex, systolic blood pressure, estimated glomerular filtration rate, and prior atrial fibrillation on treatment effects was assessed using interaction P values. Risk of major adverse cardiovascular event was analyzed according to prior stroke. Results: A total of 106/6480 participants had a stroke (1.0 event/100 patient-years of observation [PYO]). Semaglutide reduced incidence of any stroke versus placebo (0.8 versus 1.1 events/100 PYO; hazard ratio, 0.68 [95% CI, 0.46-1.00]; P=0.048), driven by significant reductions in risk of small-vessel occlusion (0.3 versus 0.7 events/100 PYO; hazard ratio, 0.51 [95% CI, 0.29-0.89]; P=0.017). Hazard ratios for risk of any stroke with semaglutide versus placebo were 0.60 (95% CI, 0.37-0.99; 0.5 versus 0.9 events/100 PYO) and 0.89 (95% CI, 0.47-1.69; 2.7 versus 3.0 events/100 PYO) in those without and with prior stroke, respectively. Except for prior atrial fibrillation (Pinteraction=0.025), no significant interactions were observed between treatment effects on risk of any stroke and subgroups investigated, or between treatment effects on risk of major adverse cardiovascular event and prior stroke (Pinteraction>0.05 for all). Conclusions: Semaglutide reduced incidence of any first stroke during the trials versus placebo in people with type 2 diabetes at high cardiovascular risk, primarily driven by small-vessel occlusion prevention. Semaglutide treatment, versus placebo, lowered the risk of stroke irrespective of prior stroke at baseline. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01720446 and NCT02692716.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Stroke |
| Vol/bind | 53 |
| Udgave nummer | 9 |
| Sider (fra-til) | 2749-2757 |
| Antal sider | 9 |
| ISSN | 0039-2499 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
Dr Strain has received speaker honoraria, conference sponsorship, and unrestricted educational grants from, and/or attended meetings sponsored by, AstraZeneca, Bayer, Eli Lilly, Janssen, Merck, Napp, Novartis, Novo Nordisk, Sanofi Aventis, and Takeda. Dr Strain is supported by the National Institute for Health and Care Research (NIHR) Exeter Clinical Research Facility. The views expressed in this publication are those of the authors and not necessarily those of the NIHR Exeter Clinical Research Facility, the NHS, the NIHR or the Department of Health in England. Dr Frenkel is a Novo Nordisk employee and stockholder. Previous employment at Roche Pharmaceuticals. Dr James has received honoraria and support for conference expenses from Daiichi-Sankyo, Amgen, Portola, and Medtronic. Dr Leiter has received honoraria for advisory board participation from, and has provided continuing medical education on behalf of, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Pfizer, Sanofi, and Servier; and has received research grants from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Lexicon, Novo Nordisk, and Sanofi. Dr Rasmussen is a Novo Nordisk employee and stockholder. Dr Rothwell has received honoraria for advisory board or trial committee participation from Abbott, Bayer, and Bristol Myers Squibb. Dr Ripa is a Novo Nordisk employee and stockholder. Dr Truelsen has received honoraria for advisory board participation from Boehringer Ingelheim, Medtronic, and Novo Nordisk; speaker honoraria from Boehringer Ingelheim, Medtronic, Bristol Myers Squibb, and AstraZeneca; research grants from Novo Nordisk Foundation; and consultancy fees from Janssen Biotech. Dr Husain has received personal fees from Boehringer Ingelheim and Janssen Inc. for advisory panel consultancy and speaker honoraria; grants and personal fees from AstraZeneca and Merck & Co for advisory panel consultancy and investigator-initiated clinical and preclinical research; personal fees from Roche for advisory panel consultancy; and grants and personal fees from Novo Nordisk for advisory panel consultancy, speaker honoraria, and investigator-initiated preclinical research. Provisional patent for methods for inhibiting platelet aggregation using GLP-1 (glucagon-like peptide-1) receptor agonists, patent No. US61/721,819; patent issued for peptides and methods for preventing ischemic tissue injury, patent No. US61/719,075.
Funding Information:
This study was funded by Novo Nordisk A/S (Søborg, Denmark). Writing and editorial assistance was provided by Jin Heppell, PhD, and Izabel James‚ MBBS‚ of Ashfield MedComms, funded by Novo Nordisk A/S (Søborg, Denmark).
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© 2022 Lippincott Williams and Wilkins. All rights reserved.
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