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World J Diabetes. Jun 15, 2017; 8(6): 270-277
Published online Jun 15, 2017. doi: 10.4239/wjd.v8.i6.270
Effects of glucose-lowering agents on ischemic stroke
Konstantinos Avgerinos, Konstantinos Tziomalos
Konstantinos Avgerinos, Konstantinos Tziomalos, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece
Author contributions: Avgerinos K drafted the review; Tziomalos K critically revised the draft.
Conflict-of-interest statement: All authors declare no conflict of interest related to this publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Konstantinos Tziomalos, MD, PhD, Assistant Professor of Internal Medicine, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 1 Stilponos Kyriakidi Street, 54636 Thessaloniki, Greece. ktziomal@auth.gr
Telephone: +30-2310-994621 Fax: +30-2310-994773
Received: January 30, 2017
Peer-review started: February 12, 2017
First decision: March 28, 2017
Revised: April 20, 2017
Accepted: May 3, 2017
Article in press: May 5, 2017
Published online: June 15, 2017
Processing time: 135 Days and 22 Hours
Abstract

Diabetes mellitus (DM) is a major risk factor for cardiovascular events, including ischemic stroke. Moreover, ischemic stroke appears to be more severe in these patients and to be associated with less favorable outcomes. However, strict glycemic control does not appear to reduce the risk of ischemic stroke. On the other hand, newer glucose-lowering agents (glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors) reduced the risk of cardiovascular events in recent randomized, placebo-controlled trials. Semaglutide also reduced the risk of ischemic stroke. These benefits are independent of glucose lowering and might be due to the favorable effects of these agents on body weight and blood pressure. Pioglitazone also reduced the risk of recurrent stroke in patients with insulin resistance or type 2 DM but the unfavorable safety profile limits its use. In contrast, sulfonylureas and dipeptidyl peptidase 4 inhibitors have a neutral effect on cardiovascular morbidity and might be less attractive options in this high-risk population.

Keywords: Antidiabetic treatment, Ischemic stroke, Cardiovascular events, Glucose regulation, Neuroprotection

Core tip: Diabetes mellitus is a major risk factor for ischemic stroke. However, strict glycemic control does not appear to reduce the risk of ischemic stroke. On the other hand, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors reduce the risk of cardiovascular events. These benefits are independent of glucose lowering and might be due to favorable effects on weight and blood pressure. Pioglitazone also reduced the risk of recurrent stroke but the unfavorable safety profile limits its use. Finally, sulfonylureas and dipeptidyl-peptidase-4 inhibitors have neutral effects on cardiovascular morbidity and might be less attractive options.