DPP4 INHIBITORS EFFICACY AND MECHANISM OF ACTION DPP

DPP-4 INHIBITORS EFFICACY AND MECHANISM OF ACTION

DPP IV ACTION/INHIBITION GIP [1 -42] GLP-1 [7 -36 amide] (biologically active) DPP IV action/ inhibition GIP [3 -42] 127945 -5/04 GLP-1 [9 -36 amide] (biologically inactive)

EFFECT OF SITAGLIPTIN ON Hb. A 1 c: CHANGE FROM BASELINE (Hb. A 1 c ~ 8. 0%) Diabetes Care 29: 2638, 2006; Clin Ther 28: 1556, 2006; Diabetolgia 49: 2564, 2006 Hb. A 1 c(%) 0 -0. 5 -0. 60 -0. 67 -0. 85 -1. 0 Drug Naive Metformin Pioglitazone ADDITION OF SITAGLIPTIN TO

EFFECT OF SAXAGLIPTIN ON Hb. A 1 c: CHANGE FROM PLACEBO (BASELINE Hb. A 1 c ≈ 8. 0%) Int J Clin Prac 63: 1395, 2009; Diab Ob Metab 10: 376, 2008 Diab Care 32: 1649, 2009; JCEM 94: 4810, 2009 Hb. A 1 c (%) 0 -0. 5 -0. 63 -0. 64 -0. 76 -1 DRUG NAIVE GLYBURIDE -0. 83 METFORMIN ADDITION OF SAXAGLIPTIN TO: PIO/ROSI

DPP-4 Combo

ADDITION OF LIRAGLUTIDE VERSUS SITAGLIPTIN IN 665 METFORMIN-TREATED T 2 DM PATIENTS (Hb. A 1 c = 8. 4%) Pratley RE, Lancet 375: 1447 -56, 2010 Decrement in Hb. A 1 c (%) 0 SITA LIRA - 1. 2 mg LIRA - 1. 8 mg 0. 5 0. 9% 1 1. 5 2 1. 2% P<0. 0001 1. 5% P<0. 0001

OMINOUS OCTET Decreased Incretin Effect Decreased Insulin Secretion Increased Lipolysis Islet–a cell HYPERGLYCEMI A Increased Glucagon Secretion Increased HGP Increased Glucose Reabsorption Decreased Glucose Uptake Neurotransmitter Dysfunction De. Fronzo RA, Diabetes 58: 773 -795, 20