Linagliptin Exerts an Anti-Inflammatory Effect in Well Controlled Patients with Type 2 Diabetes
Presentation Number: LB SUN 80
Date of Presentation: April 2nd, 2017
Husam Ghanim*1, Manav Batra2, Jeanne Hejna3, Kelly Green4, Monique Saran1, Robin Jindal1, Nitesh D Kuhadiya5 and Paresh Dandona5
1State University of New York at Buffalo, Buffalo, NY, 2University at Buffalo, Buffalo, NY, 3Suny at Buffalo, 4SUNY at Buffalo, 5Diabetes and Endocrinology Center of Western New York, Buffalo, NY
We have previously shown an acute and a long term anti-inflammatory effect of sitagliptin, a DPP-IV inhibitor, in patients with type 2 diabetes. We have now investigated the potential anti-inflammatory of linagliptin in patients with well controlled type 2 diabetes. Thirty four patients with well controlled type 2 diabetes were divided into 2 groups of 17 patients each. One group was treated with linagliptin 5 mg daily and the other was treated with placebo. Blood samples were collected prior to up to 6h after the first dose of linagliptin and thereafter at 2, 6 and 12 weeks. A suppression of reactive oxygen species (ROS) generation by mononuclear cells (MNC) and polymorphnuclear cells (PMN), by and the expression of JNK-1 and CD26 in MNC, by 16±6% and 15±5%, respectively, was observed acutely following a single dose of linagliptin. At 12 weeks, HbA1c had fallen from 6.9±0.2% to 6.5±0.2%. ROS generation by PMN was significantly lower by 19±6%, plasma lipid peroxide levels measured as TBARS had fallen by 21±8% as had NFκB binding in MNC (fell by 14±5%) in fasting blood samples. The expression of IL-1β and JNK-1 had also diminished significantly by 32±8% and 21±9%, respectively at 12 weeks. Following the administration of a high fat high calorie meal, ROS generation by PMN and MNC was diminished, as was the expression of JNK-1 in the linagliptin treated group in addition to a significantly diminished glucose excursion and a trend towards increased GLP-1 and insulin secretion. We conclude that linagliptin exerts an anti-inflammatory effect even in well controlled patients with type 2 diabetes. In addition, it suppresses CD26 expression, the cellular equivalent of DPP-IV.
Disclosure: PD: Principal Investigator, Boehringer Ingelheim Pharmaceuticals. Nothing to Disclose: HG, MB, JH, KG, MS, RJ, NDK