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This program examines the effects of Exenatide Once Weekly on the cardiovascular system in patients with type 2 diabetes. It discusses the impact on blood pressure, lipid profile, and cardiovascular risk markers.

richardgriffin
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  1. Disclosure/Disclaimer All material is intended for your medical education purposes only

  2. Amylin Pharmaceuticals, Inc., San Diego, CA, USA Eli Lilly and Company, Indianapolis, IN, USA DURATION Program:Exenatide Once Weekly Effects on the Cardiovascular System

  3. Cardiovascular Disease is a Significant Cause of Mortality in Patients With Type 2 Diabetes 50 40 30 Proportion of Deaths (%) 20 10 0 IschemicHeartDisease OtherHeartDisease Diabetes Cancer Infection Other Stroke Geiss LS, et al. In: National Diabetes Data Group. Diabetes in America. 2nd ed. 1995:233-257

  4. Metabolic Components of Diabetes: ADA Treatment Recommendations Weight control through medical nutrition LDL Cholesterol A1C <7% <100 mg/dl Blood Pressure <130/80 mmHg Reductions improve microvascular complications Reductions improve macrovascular complications American Diabetes Association. Diabetes Care 2010;33(Suppl 1):S11-S61. Stratton IM, et al. BMJ 2000;321:405-412. UKPDS 33 Group. Lancet 1998;352:837-853. Fowler MG. Clin Diabetes 2008;26:77-82LDL indicates low-density lipoprotein; UKPDS, United Kingdom Prospective Diabetes Study

  5. GLP-1 receptor expression in: myocytes pericardium vascular epithelium vascular smooth muscle GLP-1 in Tissue and Animal Models of Cardiac Function • GLP-1R agonism: • increases myocardial glucose uptake • attenuates ischemic injury • limits infarct size • Improves: • stroke volume • cardiac output • ejection fraction • systemic resistance • effects are diminished by receptor antagonism • GLP-1R agonism: • leads to dose-dependent vasodilatation Ban K, et al. Circulation 2008;117:2340-2350; Bose AK, et al. Diabetes 2005;54:146-151; Nikolaidis LA, et al. Circulation 2004;110:955-961; Sonne DP, et al. Regulatory Peptides 2008;146:243-249; Timmers L, et al. J Am Coll Cardiol 2009;53:501-10; Zhao T, et al. JPET.2006;317:1106-1113.

  6. DURATION Trials: Exenatide QW Reduced Systolic Blood Pressure DURATION-3 DURATION-1 DURATION-2 2 +0.2 mmHg 1 0 -1 Δ SBP (mmHg) -2 -1.6 mmHg -3 -0.6 mmHg -4 -3.0 mmHg -5 -3.6 mmHg -3.4 mmHg -6 p<0.05 -4.7 mmHg Exenatide QW Sitagliptin Insulin glargine Byetta Pioglitazone Drucker DJ, et al. Lancet 2008;372:1240-1250; Bergenstal RM, et al. Lancet 2010, doi:10.1016/SO140-6736(10)60590-9; Diamant M, et al. Lancet 2010;375:2234-43.

  7. DURATION Trials: Exenatide QW Reduced Diastolic Blood Pressure DURATION-2 DURATION-1 DURATION-3 0 -1 Δ DBP (mmHg) -0.4 mmHg -2 -1.4 mmHg -1.7 mmHg -1.7 mmHg -3 -2.5 mmHg -4 Insulin glargine Exenatide QW Sitagliptin Byetta Pioglitazone -0.7 mmHg -1.2 mmHg Drucker DJ, et al. Lancet 2008;372:1240-1250; Bergenstal RM, et al. Lancet 2010 doi:10.1016/SO140-6736(10)60590-9; Diamant M, et al. Lancet 2010;375:2234-43.

  8. DURATION-1: Exenatide Lowered Systolic Blood Pressure Exenatide QWBL=128 mmHg Exenatide BID BL=130 mmHg * Δ SBP (mmHg) -3.4 mmHg -4.7 mmHg Time (weeks) ITT Population, N=295. *p <0.05 Adapted from Drucker DJ, et al. Lancet 2008;372:1240-1250.

  9. Exenatide QW Resulted in a Greater Systolic Blood Pressure Reduction in Patients With Higher Baseline Systolic Blood Pressure SBP ≥ 130 mmHg SBP < 130 mmHg +3.6 +2.8 +1.4 +0.8 -0.6 Δ SBP (mmHg) -4.8 -7.9 -8.1 -9.5 -11.1 EQW EBID EQW Sita Pio EQW EBID EQW Sita Pio N=75 N=83 N=96 N=102 N=100 N=72 N=65 N=69 N=58 N=66 DURATION-2 DURATION-1 DURATION-2 DURATION-1 • Drucker DJ, et al. Lancet 2008;372:1240-1250; Bergenstal RM, et al. Lancet 2010, doi:10.1016/SO140-6736(10)60590-9; Data on file, Amylin Pharmaceuticals, Inc.

  10. DURATION-1: Fasting Lipids Improved at 2 Years LS Mean (SE) for total cholesterol, LDL, HDL; Geometric LS mean (SE) for triglycerides; * = p<0.05 vs. BaselineKim T, et al. Presented at ADA, 69th Scientific Sessions; 2009; New Orleans, LA (159-OR)

  11. DURATION-1: Exenatide QW Increased Patients Achieving ADA Goals at Week 52 52-Week Evaluable Population, N=120Bergenstal RM, et al. Lancet 2010, doi:10.1016/SO140-6736(10)60590-9

  12. DURATION-2: Exenatide QW Improved Cardiovascular Risk Markers Δ BNP (%) Δ ACR (%) Δ hs-CRP (%) Baseline: 9.7 11.4 10.8 pg/mL 14.4 11.8 13.0 mg/g creatinine 2.6 2.5 2.3 mg/L p<0.05 p<0.05 * -4% -14% -7% * +33% * -1% -24% * * -16% -33% * -23% Exenatide QW, N=160 Sitagliptin, N=166 Pioglitazone, N=165 ITT population, N=491. *p<0.05 vs. baseline. Bergenstal RM, et al. Lancet 2010, doi:10.1016/SO140-6736(10)60590-9.

  13. EXSCEL Trial EXenatide Study of Cardiovascular Event Lowering Pragmatic, placebo-controlled, double-blinded trial evaluating cardiovascular outcomes in patients with type 2 diabetes Hypothesis: EQW, when used as part of usual care, lowers the risk for major macrovascular events compared to usual care alone Global trial, 9,500 patients, ~4.5 years median exposure Run jointly by Duke Clinical Research Institute and University of Oxford Diabetes Trial Unit

  14. Cardiovascular Risk and Exenatide QW Exenatide QW  Reduced Systolic Blood Pressure  Lipid profile Improved  Reduced Cardiovascular risk markers

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