1. 2015-09-02 R2. 하효정 / 이상열 교수님 NEJM 2015-07 Jennifer B. Green, M.D., M. Angelyn Bethel, M.D., Paul W. Armstrong, M.D., John B. Buse, M.D., Ph.D., Samuel S. Engel, M.D., Jyotsna Garg, M.S., Robert Josse, M.B., B.S., Keith D. Kaufman, M.D., Joerg Koglin, M.D., Scott Korn, M.D., John M. Lachin, Sc.D., Darren K. McGuire, M.D., M.H.Sc.,Michael J. Pencina, Ph.D., Eberhard Standl, M.D., Ph.D., Peter P. Stein, M.D.,Shailaja Suryawanshi, Ph.D., Frans Van de Werf, M.D., Ph.D.,Eric D. Peterson, M.D., M.P.H., and Rury R. Holman, M.B., Ch.B., for the TECOS Study Group* Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes

2. INTRODUCTION Sitagliptin (DPP-4 inhibitor) ↑action of incretin hormones, including glucagon like peptide 1 and glucose-dependent insulinotropic polypeptide, by inhibiting their breakdown.  suppressing glucagon levels & increasing endogenous insulin secretion Saxagliptin( SAVOR-TIMI 53 study), Alogliptin (EXAMINE)  elevated risk of hospitalization for heart failure. Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS)Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) : Assessed the long-term cardiovascular safety of adding sitagliptin to usual care, as compared with usual care alone

3. METHOD Study Oversight Randomized, Double-blind, Placebo-controlled Study Population Eligible patients Type 2 diabetes with established cardiovascular disease, > 50 years of age HbA1c 6.5 - 8.0% Cardiovascular disease : history of major coronary artery disease Ischemic cerebrovascular disease Atherosclerotic peripheral arterial disease Excluded patients - Had taken DPP-4 inhibitor during the preceding 3 months - Two or more episodes of severe hypoglycemia during the preceding 12 months - eGFR < 30

4. METHOD Randomization and Study Medication Sitagliptin : Dose of 100 mg daily (or 50 mg daily if 30 < eGFR < 50) HbA1c : measured at enrollment, at 4 and 8 months, and then annually Outcomes Primary composite cardiovascular outcome :The first confirmed event of cardiovascular death Nonfatal myocardial infarction, Nonfatal stroke Hospitalization for unstable angina Secondary outcomes :the individual components of the primary composite cardio-vascular outcome Fatal and nonfatal myocardial infarction, Fatal and nonfatal stroke Death from any cause, Hospitalization for heart failure

5. RESULTS

6. 2008. 12 – 2012. 7 Mean HbA1c 7.2 +- 0.5 Living with DM 11.6 +- 8.1 years

7. RESULT Glycemic control 0.4 % 0.29 %

8. RESULT Primary and Secondary composite cardiovascular outcomes

10. RESULT Other Secondary Outcomes

11. RESULT Safety Outcomes There was no significant difference at infections, cancer, site-reported renal failure, or severe hypoglycemia. Confirmed pancreatic cancers : 9 [0.1%] vs 14 [0.3%] The rate of death from non-cardiovascular causes was 2.3% in the two study groups, with no notable differences in individual causes No clinically relevant differences in the incidence of additional clinical events of interest or serious adverse events were noted

12. CONCLUSIONS Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events.