Abstract 12647: Linagliptin Reduces Arterial Stiffness and Arterial Inflammation in Persons With Early Type 2 Diabetes: a Double-blind, Randomized Controlled Trial

Introduction: Dipeptidyl peptidase (DPP)-4 inhibitors are a class of oral antidiabetic drugs. Recent experimental studies have suggested beneficial vascular effects, but clinical evidence is limited. Hypothesis: The primary objective was to evaluate the effects of the DPP-4 inhibitor linagliptin on aortic pulse wave velocity (PWV) as a measure of arterial stiffness and secondarily, on arterial 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) uptake as a measure of arterial inflammation in type 2 diabetes. Methods: A total of 45 treatment naive type 2 diabetes patients (median age 63 (IQR 54-66) years, 61% male, mean HbA1c 6.3±0.4 (%)) without cardiovascular disease were randomized (1:1) to linagliptin 5 mg or placebo for 26 weeks in a double-blind fashion. PWV was assessed at baseline, 4, 26 weeks of treatment and at 30 weeks (washout). Arterial inflammation was quantified by FDG uptake as the pre-scan glucose corrected maximal standardized uptake value corrected for background (TBR). TBRs were calculated for the carotid arteries, ascending aorta and aortic arch, descending and abdominal aorta, and iliac and femoral arteries, and averaged for the total aortic tree ( mean TBR). Results: PWV decreased in the linagliptin group and was stable placebo (Figure A). The generalized linear model analysis showed a mean group difference of linagliptin compared to placebo of 0.91 m/s [95% CI 0.06-1.76](p=0.035) at 26 weeks. PWV returned to baseline after washout. mean TBR decreased in the linagliptin group compared with placebo by 0.18 [0.04-0.32] (p=0.015) after 26 weeks (Figure B). Linagliptin compared with placebo decreased HbA1c (p<0.001), fasting plasma glucose (p=0.002), and triglycerides (p=0.019). Conclusions: Linagliptin reduces aortic PWV as a measure of arterial stiffness and arterial FDG uptake as a measure of arterial inflammation compared with placebo after 26 weeks of treatment in early type 2 diabetes patients.