Transcript
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
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CVA
(%)
CV
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h, M
I or i
sche
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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.