New Drug Update 2009-2010 - LAFP

Table 1. Pharmacokinetics of Saxagliptin and Sitagliptin
Saxagliptin
Sitagliptin
T max
a
2 h 1 to 4 h
Half-life 2.5 h 12.4 h
Protein binding Negligible 38%
Metabolism CYP3A4/5 Minor
Active metabolite Yes No
Elimination Urine; 70% as metabolites, 12% to 29% unchanged drug Urine; 79% unchanged drug
a T max = time to maximum plasma concentration.
COMPARATIVE EFFICACY: Saxagliptin monotherapy was assessed in a 12-week, randomized, doubleblind,
placebo-controlled study enrolling 423 drug-naive patients with type 2 diabetes and inadequate
glycemic control (baseline A 1c between 6.8% and 9.7%). Mean baseline A 1c was 7.7% to 8%. Mean age
was 51.4 to 55.2 years; approximately 60% were men and approximately 85% were white. Following a 2-
week washout period, patients received saxagliptin 2.5, 5, 10, 20, or 40 mg, or placebo once daily for 12
weeks (low-dose cohort) or saxagliptin 100 mg or placebo once daily for 6 weeks (high-dose cohort). The
primary outcome was the saxagliptin dose response assessed as change in A 1c from baseline at week 12.
Saxagliptin reduced A 1c by 0.7% to 0.9% from an average baseline of 7.9% compared with a 0.27%
reduction with placebo (P < 0.007). Placebo-subtracted adjusted mean changes from baseline to week 12
for saxagliptin ranged from −0.45% to −0.63%. An A 1c of less than 7% was achieved in 41% to 53% of
saxagliptin-treated patients with a baseline A 1c of 7% or more compared with only 20% of placebo
recipients. Placebo-subtracted reductions in fasting serum glucose were 14 to 25 mg/dL in the low-dose
cohort. Postprandial glucose levels at 60 minutes after a meal were reduced 24 to 41 mg/dL compared
with placebo. Additional study results are summarized in Table 2. In the high-dose cohort, the mean
change in A 1c following 6 weeks of therapy was −1.09% in the saxagliptin group compared with −0.36% in
the placebo group. Of the patients with an A 1c of 7% or more than baseline, an A 1c of less than 7% was
achieved in 66% on saxagliptin compared with 22% on placebo. Reductions in fasting serum glucose
were evident within 2 weeks in all saxagliptin-treatment groups. (Diabetes Obes Metab. 2008;10(5):376-
386)
Table 2. Results of the Saxagliptin Dose-Ranging Study in the Treatment
of Patients With Type 2 Diabetes
Placebo
Saxagliptin
2.5 mg 5 mg 10 mg 20 mg 40 mg
A 1c < 7% 10/50
(20%)
20/40 (50%) 16/34 (47%) 20/49 (41%) 21/42
(50%)
21/40
(53%)
A 1c adjusted mean
change from baseline
(95% CI a )
−0.27
(−0.49 to
−0.05)
−0.72
(−0.97 to
−0.48)
−0.9
(−1.17 to
−0.63)
−0.81
(−1.03 to
−0.58)
−0.74
(−0.98 to
−0.5)
−0.8
(−1.04 to
−0.56)
Fasting serum glucose
adjusted mean change
from baseline (95% CI)
2.81 mg/dL
(−5.25 to
10.87)
−10.85
mg/dL
(−19.92 to
−1.77)
−21.68
mg/dL
(−31.11 to
−12.24)
−15.91
mg/dL
(−24.1 to
−7.71)
−13.61
mg/dL
(−22.42 to
−4.8)
−16.36
mg/dL
(−25.42 to
−7.3)
Postprandial glucose at
60 min, adjusted mean
change from baseline
(95% CI)
−1.41
mg/dL
(−13.39 to
10.56)
−24.42
mg/dL
(−37.67 to
−11.16)
−35.3
mg/dL
(−50.75 to
−19.86)
−41.04
mg/dL
(−53.13 to
−28.94)
−27.54
mg/dL
(−41.27 to
−13.8)
−33.98
mg/dL
(−47.2 to
−20.75)
Body weight mean −1.03 kg −0.94 kg −0.23 kg −1.28 kg −0.11 kg 0.51 kg
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