Dulaglutide may reduce stroke in T2D

The GLP-1 receptor agonist* dulaglutide may reduce the incidence of stroke, particularly ischaemic stroke, in individuals with type 2 diabetes (T2D) and cardiovascular (CV) risk factors, according to findings of an exploratory analysis of the REWIND** trial.

The multinational trial involved 9,901 individuals aged ≥50 years with T2D (HbA_1c ≤9.5 percent), BMI ≥23 kg/m², and cardiovascular (CV) risk factors on stable doses of ≤2 oral glucose-lowering drugs (with or without basal insulin). They were randomized to receive either subcutaneous dulaglutide (1.5 mg/week) or placebo. About 93 percent of patients had hypertension at baseline, 9.1 percent had a history of stroke or transient ischaemic attack (TIA), and 6.4 percent had a history of atrial fibrillation (AF). Participants continued using their guideline-directed medical therapies during the trial.

Over the median 5.4-year follow-up period, the incidence of fatal or non-fatal stroke was significantly reduced among patients who received dulaglutide compared with placebo recipients (3.2 percent vs 4.1 percent; hazard ratio [HR], 0.76, 95 percent confidence interval [CI], 0.62–0.94; p=0.010). [Lancet Diabetes Endocrinol 2020;doi;10.1016/S2213-8587(19)30423-1]

The reduction in stroke incidence with dulaglutide was specific to ischaemic stroke (HR, 0.75, 95 percent CI, 0.59–0.94; p=0.012), with no apparent effect on the incidence of haemorrhagic stroke (HR, 1.05, 95 percent CI, 0.55–1.99; p=0.89), unknown type of stroke (HR, 0.82, 95 percent CI, 0.40–1.66; p=0.58), or TIA (HR, 0.79, 95 percent CI, 0.52–1.20; p=0.27).

There was also a reduction in non-fatal stroke with dulaglutide vs placebo (HR, 0.76, 95 percent CI, 0.61–0.95; p=0.017) as well as disabling stroke*** (HR, 0.74, 95 percent CI, 0.56–0.99; p=0.042), but no impact on fatal stroke (HR, 0.78, 95 percent CI, 0.47–1.30; p=0.34), though the number of events for this outcome was small (n=26 vs 33). There was also a significant reduction in the composite of non-fatal stroke or all-cause death with dulaglutide vs placebo (HR, 0.88, 95 percent CI, 0.79–0.98; p=0.017).

The reduction in stroke with dulaglutide was comparable across multiple subgroups, including age, sex, systolic blood pressure, AF, HbA_1c, history of cardiovascular or cerebrovascular disease, or use of renin-angiotensin system medications or statins.

Additional exploratory analyses suggested that the effect of dulaglutide on stroke reduction may be attributed to several factors including the reduction in systolic blood pressure or HbA_1c, which accounted for up to 14 and 54 percent of the effect, respectively. “[However], much of the effect of dulaglutide on stroke could be due to mechanisms that are independent of these two risk factors,” noted the researchers.

“[This study] meaningfully supports the consideration of GLP-1 receptor agonists for stroke prevention in people with T2D at increased CV risk,” said Dr Vanita Aroda from Brigham and Women’s Hospital, Boston, Massachusetts, US, in an editorial. [Lancet Diabetes Endocrinol 2020;doi:10.1016/S2213-8587(19)30427-9]

“[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,” the researchers added.