Impact of glucose-lowering therapies on risk of stroke in type 2 diabetes.

[en] Patients with type 2 diabetes (T2D) have an increased risk of stroke compared with people without diabetes. However, the effects of glucose-lowering drugs on risk of ischaemic stroke in T2D have been less extensively investigated than in coronary heart disease. Some evidence, including the UKPDS, has suggested a reduced risk of stroke with metformin, although the number of studies is limited. Inhibition of the KATP channels increases ischaemic brain lesions in animals. This is in agreement with a recent meta-analysis showing an increased risk of stroke with sulphonylureas vs. various comparators as both mono- and combination therapy. Pioglitazone can prevent recurrence of stroke in patients with previous stroke, as already shown in PROactive, although results are less clear for first strokes. As for DPP-4 inhibitors, there was a non-significant trend towards benefit for stroke, whereas a possible increased risk of stroke with SGLT2 inhibitors-and in particular, empagliflozin in the EMPA-REG OUTCOME trial-has been suggested and requires clarification. Experimental results support a potential protective effect of GLP-1 receptor agonists against stroke that has, at least in part, been translated to clinical benefits in T2D patients in the LEADER and SUSTAIN-6 trials. Further interventional studies are now warranted to confirm the effects of glucose-lowering agents on risk of stroke in patients with T2D. In summary, the effects of antidiabetic drugs on risk of stroke appear to be heterogeneous, with some therapies (pioglitazone, GLP-1 receptor agonists) conferring possible protection against ischaemic stroke, other classes showing a neutral impact (DPP-4 inhibitors, insulin) and some glucose-lowering agents being associated with an increased risk of stroke (sulphonylureas, possibly SGLT2 inhibitors, high-dose insulin in the presence of insulin resistance).

Disciplines :

Pharmacy, pharmacology & toxicology
Endocrinology, metabolism & nutrition

Author, co-author :

Bonnet, Fernand ; Centre Hospitalier Universitaire de Rennes

Scheen, André ; Université de Liège > Département des sciences cliniques > Département des sciences cliniques

Language :

English

Title :

Impact of glucose-lowering therapies on risk of stroke in type 2 diabetes.

Publication date :

2017

Journal title :

Diabetes and Metabolism

ISSN :

1262-3636

eISSN :

1878-1780

Publisher :

Elsevier Masson, Paris, France

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 16 November 2017

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