Effect of antidiabetic treatment on incidence of stroke in patients with type 2. diabetes

Overview

Stroke occurs more than twice as often in patients with diabetes compared to the non-diabetic population of the same age. Diabetes mellitus is a strong risk factor, especially for ischemic strokes, which account for approximately 90% of all strokes. The incidence of stroke is favourably influenced by LDL-cholesterol-lowering therapy as well as anti­hypertensive therapy, especially renin-angiotensin system inhibitors. Studies which aimed at achieving the best possible glycemic control have failed to demonstrate the benefit of better diabetic control in preventing the development of stroke. Among the different groups of newer antidiabetic drugs, the benefit of DPP-4 inhibitors, SGLT2 inhibitors, or insulin analogues in preventing the development of stroke has not been demonstrated. A meta-analysis of studies with glitazones showed a beneficial effect of this group of drugs in preventing the development of stroke, but their serious side effects have led to their limited use in the last decade. GLP-1 receptor agonists (GLP1-RA) as adjunctive therapy in trials with semaglutide and dulaglutide have demonstrated the ability to reduce the incidence of stroke significantly compared with placebo. Similarly, a meta-analysis of eight trials published to date with GLP1-RA showed a significant 17% reduction in the incidence of stroke. The protective effect of GLP1-RA against stroke is mediated by multiple mechanisms. GLP1-RA exert an antiatherogenic effect in all arterial beds mediated by the interactions with the process of atherogenesis at the level of endothelium, media, platelet aggregation, and other tissues. In addition, GLP1-RA also appear to have a protective effect directly in the brain, which, in addition to a preventive effect against the development of stroke, is manifested by a reduction in the ischemic loci with GLP1-RA treatment.

Keywords:

atherosclerosis- GLP-1 receptor agonists – preventive effect – stroke