1. Study Design Scirica BM, Bhatt DL Braunwald et al, Sexagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013 Oct 3;369(14):1317-1326

2. Study Design White WB, Cannon CP, Heller SR et al, Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013 Oct 3;369(14):1327-1335

3. SAVOREXAMINE Primary end-point composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke DesignMulticenter, double blind and randomized Treatment Saxagliptin vs placebo in addition to existing antihyperglycemic therapy Alogliptin vs placebo in addition to existing antihyperglycemic therapy Patients16 4925 380 Follow-up2.1 years18 months Study Design

4. Change in HbA 1c SAVOREXAMINE  HbA 1c (at the end of the trial) -0.3%-0.36% % HbA 1c <7% (at the end of the trial) 36.2%-

5. SAVOREXAMINE Major 2.1% (vs 1.7%; P=0.047)0.7% (vs 0.6; P=0.86) Hospitalization 0.6% (vs 0.5%; P=0.33)- Minor 14.2% (vs 12.5; P=0.002)- At least 1 hypoglycemic event 15.3% (vs 13.4%; P<0.001)- Any hypoglycemia* (AE) -6.7% (vs 6.5%; P=0.74) A hypoglycaemic event can be either: An episode with symptoms and confirmed low glucose (<3 mmol/L) An episode with low glucose An episode with symptoms when glucose was not measured Major hypoglycaemic events are events requiring the assistance of another person to actively administer carbohydrates, glucagons, or other resuscitative actions. Minor hypoglycaemic events are considered when there is an awareness of the event, the event is tolerated, and the patient recovers by her/himself. In addition, the events resolved within 30 minutes of ingestion of carbohydrates (if possible confirmed with a fingerstick value). A measurement of blood glucose <54 mg/dL (<3.0 mmol/L) without symptoms is also considered an adverse event. Hypoglycemia

6. 8 4 6121824 CV death, MI or ischemic CVA (%) Months 2y KM 2y KM Saxagliptin 7.3% Placebo 7.2% HR 1.00 [0.89-1.12] P<0.001 (non-inferiority) 10 14 12 6 2PlaceboSaxagliptin7983807177617836726773134855492082128280 Primary end point Scirica BM, Bhatt DL Braunwald et al, Sexagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013 Oct 3;369(14):1317-1326

7. Placebo (N=8 212) Saxagliptin (N=8 280) HR P-value for superiority CV death 2.93.21.03 (0.87-1.22)0.72 MI 3.43.20.95 (0.80-1.12)0.52 Ischemic stroke 1.71.91.11 (0.88-1.39)0.38 Hosp for cor. revasc 5.65.20.91 (0.80-1.04)0.18 Hosp for UA 1.01.21.19 (0.89-1.60)0.24 Hosp for heart failure 2.83.5 1.27 (1.07-1.51) 0.007 All-cause mortality 4.24.91.11 (0.96-1.27)0.15 2-year KM rate (%) Individual end points Significantly more patients in the saxagliptin group than placebo were hospitalized for heart failure Scirica BM, Bhatt DL Braunwald et al, Sexagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013 Oct 3;369(14):1317-1326

8. Primary end point White WB, Cannon CP, Heller SR et al, Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013 Oct 3;369(14):1327-1335

9. Hospitalization for heart failure: pooled analysis Sattar N, Results from SAVOR and EXAMINE. DPP-4 inhibitors and CVD, EASD 2013 Sep 26.