Impact of glucose lowering drugs drugs on stroke risk

Abstract

Stroke is 2 times more common in people with diabetes than in people without diabetes. Hence the importance of knowing the impact of drugs used for glycemic control on stroke risk.

With metformin, the evidence is sparse, and comes from the UKPDS and a meta-analysis, where a neutral effect for stroke was observed. The group of sulfonylureas pose the difficulty of being a heterogeneous group, in the ADVANCE trial, with Gliclazide no increase in stroke was seen, but a meta-analysis comparing sulfonylureas with other antidiabetics, showed an increased risk of stroke with these drugs. Pioglitazone, in the Proactive trial in population with DM2, a reduction in stroke risk was observed; as in the IRIS study in population without type 2 diabetes, but with insulin resistance and a recent cerebrovascular event, Pioglitazone had a protective effect. Nateglinide in the Navigator trial was shown to have a neutral effect. CVOTs and meta-analyses with DPP-4 inhibitors also show a neutral effect on stroke risk. With SGLT-2 inhibitors, there are two meta-analyses that show a neutral effect on stroke in general, however one of them shows a protective effect on hemorrhagic stroke.GLP-1 agonists have a protective effect in meta-analyses, but only CVOTs with Dulaglutide and Semaglutide have shown benefit in stroke. With insulin the effect is neutral, the most recent data come from the Origin and Devote trials.

In conclusion, in secondary prevention should be prioritized, for its benefits, the use of Pioglitazone, Semaglutide or Dulaglutide; there is some evidence of a negative effect with the use of sulfonylureas; whith other antidiabetics do not cause increased risk of stroke.