Linagliptin Increases Incretin Levels, Lowers Glucagon, and Improves Glycemic Control in Type 2 Diabetes Mellitus

• DOI: 10.1007/s13300-012-0010-y
• Publication Date: 2012-09-17T09:41:54Z
• Authors: Thomas Rauch; Ulrike Graefe-Mody; Carolyn F. Deacon; Arne Ring; Jens J. Holst; Hans-Juergen Woerle; Klaus A. Dugi; Tim Heise
• Keywords: Linagliptin; Glycated hemoglobin; Dipeptidyl peptidase-4 inhibitor

Linagliptin is a xanthine-based dipeptidyl peptidase (DPP)-4 inhibitor that now available in numerous countries worldwide for the treatment of type 2 diabetes mellitus (T2DM). The aim this study was to evaluate further mechanisms underlying improvements glycemic control observed with linagliptin. effects linagliptin on DPP-4, pharmacodynamic parameters, and versus placebo were assessed patients inadequately controlled T2DM.Patients phase 2a, multicenter, randomized, double-blind, placebo-controlled received (n = 40) or 5 mg 40). Sitagliptin 100 41) once daily 4 weeks included exploratory purposes. Primary endpoints placebo: change from baseline day 28 24-h weighted mean glucose (WMG) intact glucagon-like peptide (GLP)-1 area under time-effect curve between 0 h (AUEC(0-2h)) following meal tolerance test 28.Linagliptin increased GLP-1 AUEC(0-2h) (+18.1 pmol/h/L) lowered WMG (-1.1 mmol/L) (both P < 0.0001) after days. Intact glucose-dependent insulinotropic polypeptide line (+91.4 pmol/h/L increase vs. placebo; 0.0001). Glycated hemoglobin (-0.22%; 0.0021), fasting plasma (-0.6 mmol/L; 0.0283), (AUEC(0-3h)) (-5.9 mmol/h/L; improved significantly placebo. Most adverse events mild; hypoglycemia serious not reported. Sustained DPP-4 inhibition (≥80%) throughout period accompanied by significant reductions glucagon starting at 1 administration.Linagliptin well tolerated effectively inhibited activity T2DM, producing immediate incretin levels, suppression, maintained period.