REWIND supports stroke protective effect for GLP-1 receptor agonists
medwireNews: An exploratory analysis of stroke outcomes in the REWIND trial indicates that dulaglutide may reduce the incidence but not severity of ischemic stroke in people with type 2 diabetes.
Hertzel Gerstein (McMaster University and Hamilton Health Sciences, Ontario, Canada) and study co-authors say the results are in line with positive effects on stroke risk that have emerged from other cardiovascular outcomes trials for the glucagon-like peptide (GLP)-1 receptor agonist class.
“[G]iven the frequency of stroke in people with diabetes, the severity of its associated morbidity, and the paucity of preventive therapies, the findings of this study suggest that GLP-1 receptor agonists should be considered when developing future stroke prevention guidelines for people with diabetes,” they write in The Lancet Diabetes & Endocrinology.
Stroke occurred in 3.2% of the 4949 REWIND participants taking dulaglutide and 4.1% of the 4952 taking placebo over a median 5.4 years, giving a significant 24% risk reduction in favor of dulaglutide. This was mostly accounted for by a 24% reduction in nonfatal stroke events; there were only 59 fatal strokes, so the 22% risk reduction seen with dulaglutide for this outcome was not significant.
The vast majority of strokes were ischemic, and dulaglutide reduced their incidence by a significant 25%, whereas there was no sign of an effect on the risk for hemorrhagic stroke, which occurred in 0.4% of both groups. Dulaglutide reduced ischemic stroke risk regardless of whether or not participants had a history of stroke or transient ischemic attack at baseline.
But despite the association with reduced stroke incidence, dulaglutide did not appear to reduce the severity of those strokes that did occur. The distribution of scores on the modified Rankin Scale, which quantifies functional outcomes after stroke (from 0=no impairment to 6=death), was not significantly different according to whether the patients had been taking dulaglutide or placebo.
The researchers found that the glucose-lowering effect of dulaglutide accounted for up to 54% of its effect on stroke risk. And its effect on blood pressure (it lowered systolic blood pressure by an average 1.7 mmHg) accounted for a further 14%.
In a linked commentary, Vanita Aroda (Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA) says: “These findings reinvigorate the importance of glycaemic control in the modern era, in which current pharmacological tools and approaches might favourably address both glycaemia and clinical indicators of cardiovascular risk (blood pressure, weight, and lipids).”
However, she cites “a growing body” of preclinical data supporting a specific protective effect of GLP-1 receptor agonism against stroke, and notes the lack of a consistent association in clinical trials of other effective glucose-lowering drug classes such as the sodium-glucose cotransporter 2 inhibitors.
Aroda therefore concludes that this REWIND analysis “meaningfully supports the consideration of GLP-1 receptor agonists for stroke prevention in people with type 2 diabetes at increased cardiovascular risk.”
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