In This Issue of Diabetes
Edited by Helaine E. Resnick, PhD, MPH
A Case for the Development of DPP-4 Inhibitors for Stroke Prevention in Diabetes?
The study by Darsalia et al. shows that linagliptin, a drug currently in use against type 2 diabetes, may also protect against stroke. In this issue of Diabetes (p. 1289), the investigators studied the antistroke efficacy of linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in type 2 diabetic mice. Type 2 diabetes is a risk factor for stroke, and stroke patients with diabetes have a greater risk of stroke recurrence and mortality than nondiabetic stroke patients. Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists are in clinical use against type 2 diabetes. GLP-1R activation can also occur by prolonging the half-life of endogenous GLP-1 via inhibition of DPP-4. In a first set of experiments, 25-week-old obese diabetic mice were treated with either 10 mg/kg/body weight linagliptin per day or 2 mg/kg/body weight sulfonylurea glimepiride per day or vehicle for 7 weeks. Glimepiride was chosen because it does not affect the incretin system. At 4 weeks into the treatment, stroke was induced by transient middle cerebral artery occlusion. In a second set of experiments, 10-week-old control mice were treated with linagliptin, glimepiride, or vehicle for 7 weeks, similar to the first experiment. Again, all mice were subjected to stroke at 4 weeks. Linagliptin was efficacious against stroke in both type 2 diabetic mice and control mice. However, glimepiride showed antistroke efficacy only in control mice. The investigators propose that glimepiride’s neuroprotective effects are mediated by increased …