Neuroprotective effect of glucagon-like peptide-1 receptor agonist is independent of glycaemia normalization in type two diabetic rats

Objective: Stroke is a severe complication of type 2 diabetes mellitus. Glucagon-like peptide-1 receptor agonists have been shown to have a neuroprotective effect in experimental diabetes. The aim of this study was to determine if their neuroprotective effect is an independent property of the drug independent of glycaemic control. Methods: This two-phase study used male Wistar rats. In the first phase, experimental animals were pretreated with liraglutide, while controls received only vehicle. After transient focal brain ischaemia modelling, neurological deficit and brain infarct volume were measured. In the second phase, the first and the second groups of experimental animals with type 2 diabetes mellitus received liraglutide and metformin, respectively, while control animals with diabetes received only vehicle. After transient focal brain ischaemia modelling, neurological deficit and brain infarct volume were evaluated. Results: Pretreatment with liraglutide in diabetic and non-diabetic animals reduced infarct size as compared to controls, while only non-diabetic liraglutide-treated rats presented neurologic deficit decreases. Despite glycaemia normalization, metformin-treated diabetic rats had no differences in stroke outcome when compared to the control group. Conclusion: The neuroprotective effect of liraglutide is not associated with glycaemic control amelioration in experimental type 2 diabetes mellitus.