SLI064

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

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

SAVORSAVOR EXAMINEEXAMINE

Primary end-point composite of cardiovascular death, nonfatalmyocardial infarction, or nonfatal ischemic stroke

Design Multicenter, double blind and randomized

TreatmentSaxagliptin vs placebo

in addition to existing antihyperglycemic therapy

Alogliptin vs placeboin addition to existing

antihyperglycemic therapy

Patients 16 492 5 380

Follow-up 2.1 years 18 months

Study Design

Change in HbA1c

SAVORSAVOR EXAMINEEXAMINE

HbA1c (at the end of the trial) -0.3% -0.36%

% HbA1c <7%(at the end of the trial) 36.2% -

SAVORSAVOR EXAMINEEXAMINEMajor 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

88

44

66 1212 1818 2424

CV

deat

h, M

I or i

sche

mic

CVA

(%)

CV

deat

h, M

I or i

sche

mic

CVA

(%)

MonthsMonths

2y KM2y KMSaxagliptin Saxagliptin 7.3% 7.3%

Placebo Placebo 7.2% 7.2%

HR 1.00 [0.89-1.12]HR 1.00 [0.89-1.12]PP<0.001 (non-inferiority)<0.001 (non-inferiority)

1010

1414

1212

66

22

PlaceboPlacebo

SaxagliptinSaxagliptin

79837983

80718071

77617761

78367836

72677267

73137313

48554855

49204920

82128212

82808280

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

Placebo(N=8 212)

Saxagliptin(N=8 280) HR P-value for

superiority

CV death 2.9 3.2 1.03 (0.87-1.22) 0.72

MI 3.4 3.2 0.95 (0.80-1.12) 0.52

Ischemic stroke 1.7 1.9 1.11 (0.88-1.39) 0.38

Hosp for cor. revasc 5.6 5.2 0.91 (0.80-1.04) 0.18

Hosp for UA 1.0 1.2 1.19 (0.89-1.60) 0.24

Hosp for heart failureHosp for heart failure 2.82.8 3.53.5 1.27 (1.07-1.51)1.27 (1.07-1.51) 0.0070.007

All-cause mortality 4.2 4.9 1.11 (0.96-1.27) 0.15

2-year KM rate (%)

Individual end pointsSignificantly more patients in Significantly more patients in the saxagliptin group than the saxagliptin group than placebo were hospitalized for placebo were hospitalized for heart failureheart 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

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

Hospitalization for heart failure: pooled analysis

Sattar N, Results from SAVOR and EXAMINE. DPP-4 inhibitors and CVD, EASD 2013 Sep 26.