Contrasting Effects of Sitagliptin and Exenatide on Plasma Concentrations of Betatrophin

Presentation Number: OR23-2
Date of Presentation: June 22nd, 2014

Husam Ghanim*1, Ajay Chaudhuri2, Antoine Makdissi3, Sanaa Abuaysheh4, Kaushik Chatterjee5, Nitesh D Kuhadiya6, Manav Batra6 and Paresh Dandona7
1State University of New York at Buffalo, Buffalo, NY, 2UB Sch of Med, Williamsville, NY, 3State Univ of New York at Buffal, Buffalo, NY, 4SUNY at Buffalo, 5Suny at Buffalo, 6University at Buffalo, Buffalo, NY, 7State Univ of NY, Buffalo, NY

Abstract

Since incretin based therapies stimulate and conserve β-cell function, we investigated action of these agents on plasma concentrations of betatrophin, a peptide secreted by hepatocytes and which stimulates β-cell function and proliferation. Two groups of 12 patients each with type 2 diabetes were treated with 100 mg sitagliptin daily or placebo for 12 weeks. Fasting blood samples were obtained at 0, 2, 8 and 12 weeks. Following sitagliptin treatment, there was a significant fall in plasma FFA concentrations (by 19±11%) and HbA1c (by 0.7%) and an increase in plasma concentrations of active GLP-1 (by 63±20%). Indices of inflammation fell significantly. There was a significant increase in betatrophin concentrations at 8 and 12 weeks (by 37±13%, from 1.12±0.31ng/ml to 1.38±0.36ng/ml; p<0.05). Another series of 12 patients was treated with exenatide injections (10 µg twice daily) for 12 weeks. Fasting blood samples were obtained at baseline, 3, 6 and 12 weeks. Plasma glucose and FFA concentrations and HbA1c levels fell significantly (by 25±11%, 21±5% and 1.2%, respectively) as did the indices of inflammation. Fasting Insulin levels increased (by 31±12%). Plasma concentrations of betatrophin did not alter. Thus, sitagliptin, a DPP-IV inhibitor, which is thought to exert its effects through an increase in GLP-1, clearly stimulates betatrophin independently of this peptide since exenatide, a GLP-1 receptor agonist, has no effect on betatrophin, a potentially important mediator of β-cell proliferation and function. We conclude that sitagliptin and possibly other DPP-IV inhibitors induce betatrophin and may thus positively modulate β-cell function and proliferation through another novel mechanism.

 

Nothing to Disclose: HG, AC, AM, SA, KC, NDK, MB, PD