GLP-1 Agonists and DPP-4 Inhibitors How do they work? Part 7.

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 GLP -1 (gut hormone) + GIP = incretin effect =Augmentation of insulin after oral glucose  Type 2 diabetics little incretin effect  Reduced GLP-1 secretion.
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GLP-1 Agonists and DPP-4 Inhibitors How do they work? Part 7

Incretin Therapy and Type 2 Diabetes Mellitus

Normalization of Diurnal Plasma Glucose Concentrations by Continuous IV GLP-1

Dose-Response Effectc of Exenatide on Plasma Glucose, Insulin, and Glucagon Concentration in T2DM

Effect of Exenatide on Glycemic Control in Metformin-Treated Type 2 Diabetes 4-week placebo run-in 4 weeks of exenatide (5 µg BID) or placebo 26 weeks of exenatide (10 µg BID) or placebo Metformin dose kept constant 336 metformin-treated patients with type 2 diabetes Age: 53±10y; BMI: 34.2±5.9 A1C: 8.2±1.1% Subjects: Protocol: DeFronzo RA, et al. Diabetes Care. 2005;28:

Effect of Exenatide on A1C

Effect of Exenatide on Body Weight

Effect of Exenatide on Postprandial Glucose and Insulin Concentrations

Change in Weight by Quartile at 82 Weeks

Change in A1C as a Function of Change in Weight at 82 Weeks

Change in Triglycerides and HDL-C as Function of Weight-Change Quartile at 82 Weeks

Change in Blood Pressure as Function of Weight-Change Quartile at 82 Weeks

Exenatide Treatment: 3.5-Year Follow-up

Comparison of Exenatide vs Glargine on Glycemic Control in T2DM on MET/SU Therapy

Exenatide Reduces Postmeal Glucose Excursio ns

Once-Weekly Exenatide (LAR) vs Twice-Daily Exenatide 75% achieved A1C <7.0% 8 lb weight loss with both Nausea occurred in only 20% of LAR 295 T2DM on SU/Metformin; A1C >7.0% Once-weekly exenatide LAR (2 mg) vs twice-daily Exenatide (10 µg) for 30 wks Decrement in A1C =1.9% LAR QW vs 1.5% Exenatide BID Subjects: Study Design: Results: LAR=Long-acting release.