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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Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes : Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6. / Strain, W. David; Frenkel, Ofir; James, Martin A.; Leiter, Lawrence A.; Rasmussen, Søren; Rothwell, Peter M.; Sejersten Ripa, Maria; Truelsen, Thomas C.; Husain, Mansoor.
In: Stroke, Vol. 53, No. 9, 2022, p. 2749-2757.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes
T2 - Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6
AU - Strain, W. David
AU - Frenkel, Ofir
AU - James, Martin A.
AU - Leiter, Lawrence A.
AU - Rasmussen, Søren
AU - Rothwell, Peter M.
AU - Sejersten Ripa, Maria
AU - Truelsen, Thomas C.
AU - Husain, Mansoor
N1 - Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - atrial fibrillation
KW - blood pressure
KW - myocardial infarction
KW - peptides
KW - prevalence
U2 - 10.1161/STROKEAHA.121.037775
DO - 10.1161/STROKEAHA.121.037775
M3 - Journal article
C2 - 35582947
AN - SCOPUS:85136464668
VL - 53
SP - 2749
EP - 2757
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 9
ER -
ID: 331359112