Part 2 of 2

 GLP-1 agonists have been shown to reduce several inflammatory markers including plasminogen activa­tor inhibitor-1 (PAI-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1)  E-selectin was not significantly reduced  C-reactive protein has also been associated with increased cardiovascular disease  Patients treated with exenatide showed marked decrease in c-reactive protein levels after an 82- week study (from 3.21mg/dL to 1.35 mg/dL) Kendall DM, Bhole D, Guan X, et al.: Exenatide treatment for 82 weeks reduced C-reactive protein, HbAlc, and body weight in patients with type 2 diabetes mellitus. Presented at 42nd Congress of EASD.Copenhagen, Denmark; September 14-17, 2006.

 50,330 patients taking exenatide with insulin and another antidiabetic treatment were 57% less likely to develop heart failure compared to those that took insulin, antidiabetic treatment, but no exenatide (OR 0.43; 95% CI )  53,446 patients who received exenatide and other noninsulin therapies were 31% less likely to develop heart failure compared to those that took a noninsulin therapy and no exenatide (OR 0.69; 95% CI )  After combining data, patients who took exenatide were 54% less likely to develop heart failure than those that were not (OR 0.46; 95% CI ) Best JH, Maggs D, Little W, et al. The risk of heart failure among patients receiving exenatide twice daily versus other glucose-lowering medications for diabetes: a matched retrospective analysis of the GE Healthcare EMR data. Diabetologia 2011; 54(Suppl. 1): S1–S542.

 ↑ Cardiac output, ↓ LV end diastolic pressure, and ↑ myocardial glucose uptake in animal (rodent and dog) models of CHF and myocardial injury  ↓ Infarct size in ischemic animal models  ↑ LVEF and ↑ wall motion in humans with MI and EF <40%  GLP-1 (9-36)amide ↑ myocardial contractility (dp/dt) and glucose uptake in dogs with cardiomyopathy

Risk of Cardiovascular Disease Events in Patients With Type 2 Diabetes Prescribed the Glucagon-Like Peptide 1 (GLP-1) Receptor Agonist Exenatide Twice Daily orOther Glucose-Lowering Therapies A retrospective analysis of the LifeLink database JENNIE H. BEST, PHD, Diabetes Care 34:90–95, Exenatide and CV outcomes- 430,000 patients-near 40,000 on exenatide

Insulin Secretion β-Cell Neogenesis β-Cell Apoptosis Glucagon Secretion Glucose Production Heart GI Tract Liver Muscle Drucker DJ, Cell Metab. 2006;3: Brain Appetite Cardioprotection Cardiac Output GLP-1 Stomach Gastric Emptying Neuroprotection Glucose Uptake _ +

 GLP-1 agonists not only help reduce plasma glucose levels in type-2 diabetics, but also help improve markers of cardiovascular function including blood pressure, cholesterol, and weight loss.  GLP-1 agonists are shown to have positive effects on cardiovascular outcomes and reduce the risk for heart failure  These benefits to cardiovascular health are independent of GLP-1 agonists’ effect on glucose control and add important cardiocascular effects for type-2 diabetics.