GLP1 Agonists and DPP4 Inhibitors How do they

GLP-1 Agonists and DPP-4 Inhibitors How do they work? Part 5

Overview • Discuss normal GLP-1 physiology • Examine the actions of DPP-4 inhibitors and GLP-1 R agonists • Review the tissue-specific differences in the mechanisms of action of GLP-1 analogs, DPP-4 inhibitors, and GLP 1 R agonists

Summary of Pharmacologic Incretin Actions on Different Heart Brain Target Tissues Stomach Neuroprotection Appetite Gastric Emptying Cardioprotection Cardiac Output GLP-1 _ Liver GI Tract Insulin Secretion β-Cell Neogenesis Glucose Production Drucker DJ. Cell Metab. 2006; 3: 153 -165. Muscle + β-Cell Apoptosis Glucose Uptake Glucagon Secretion

Summary of Pharmacologic Incretin Actions on Different Heart Brain Target Tissues Stomach Neuroprotection Appetite Gastric Emptying Cardioprotection Cardiac Output GLP-1 _ Liver GI Tract Insulin Secretion β-Cell Neogenesis Glucose Production Drucker DJ, Cell Metab. 2006; 3: 153 -165. Muscle + β-Cell Apoptosis Glucose Uptake Glucagon Secretion

Effect of GLP-1 (7 -36)amide SC on Gastric Emptying

DPP-4 Inhibition With Vildagliptin Has No Effect on Gastric Emptying in Human Subjects

Exenatide Increases Gastric Half-Emptying Time (T 50) for Solid Meal (Tc-Labeled Eggs)

Summary of Pharmacologic Incretin Actions on Different Heart Brain Target Tissues Stomach Neuroprotection Appetite Gastric Emptying Cardioprotection Cardiac Output GLP-1 _ Liver GI Tract Insulin Secretion β-Cell Neogenesis Glucose Production Drucker DJ. Cell Metab. 2006; 3: 153 -165. Muscle + β-Cell Apoptosis Glucose Uptake Glucagon Secretion

GLP-1 Regulates Central Feeding Behavior

Change in Body Weight Over 24 Weeks: Sitagliptin Monotherapy Studies

Sitagliptin + Pioglitazone Are Weight Neutral Compared to Pioglitazone Alone in T 2 DM