Transcript the slide set

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
Study Design
SAVOR
Primary end-point
Design
Treatment
Patients
Follow-up
EXAMINE
composite of cardiovascular death, nonfatal
myocardial infarction, or nonfatal ischemic stroke
Multicenter, double blind and randomized
Saxagliptin vs placebo
Alogliptin vs placebo
in addition to existing
antihyperglycemic therapy
in addition to existing
antihyperglycemic therapy
16 492
5 380
2.1 years
18 months
Change in HbA1c
 HbA1c
(at the end of the trial)
% HbA1c <7%
(at the end of the trial)
SAVOR
EXAMINE
-0.3%
-0.36%
36.2%
-
Hypoglycemia
SAVOR
EXAMINE
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)
-
14.2% (vs 12.5; P=0.002)
-
15.3% (vs 13.4%; P<0.001)
-
-
6.7% (vs 6.5%; P=0.74)
Minor
At least 1
hypoglycemic event
Any hypoglycemia* (AE)
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
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.
Major hypoglycaemic events are events requiring the assistance of another person to actively administer carbohydrates,
glucagons, or other resuscitative actions.
CV death, MI or ischemic CVA (%)
Primary end point
14
HR 1.00 [0.89-1.12]
P<0.001 (non-inferiority)
12
10
2y KM
8
6
Saxagliptin
7.3%
Placebo
7.2%
4
2
6
12
18
24
Months
Placebo
8212
7983
7761
7267
4855
Saxagliptin
8280
8071
7836
7313
4920
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
Individual end points
Significantly more patients in the
saxagliptin group than placebo
were hospitalized for heart failure
2-year KM rate (%)
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 failure
2.8
3.5
1.27 (1.07-1.51)
0.007
All-cause mortality
4.2
4.9
1.11 (0.96-1.27)
0.15
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.