Efficacy and safety of saxagliptin combination therapy in US patients with type 2
diabetes.
Author(s): Karyekar C, Donovan M, Allen E, Fleming D, Ravichandran S, Chen R.
Affiliation(s): Global Clinical Research, Bristol-Myers Squibb, Princeton, NJ 08543, USA.
chetan.karyekar@bms.com
Publication date & source: 2011, Postgrad Med. , 123(4):63-70
BACKGROUND: The mechanism of action of dipeptidyl peptidase-4 inhibitors, such as
saxagliptin, makes them suitable for combination therapy in type 2 diabetes
mellitus (T2DM). Genetic, cultural, and environmental differences in individuals
from different regions of the world may result in differences in treatment
response to oral antidiabetic drugs (OADs). This post-hoc subanalysis assessed
the efficacy and safety of saxagliptin as add-on therapy to metformin, glyburide,
or a thiazolidinedione in patients with inadequately controlled T2DM in the
United States.
METHODS: In 3 phase 3 studies of patients with T2DM uncontrolled on monotherapy,
547 adult US patients were randomized to receive saxagliptin (2.5 or 5 mg/d) or
placebo as add-on to metformin, glyburide, or a thiazolidinedione (pioglitazone
or rosiglitazone). Efficacy was assessed as the change from baseline to week 24
in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial
glucose area under the curve (PPG-AUC) and the proportion of patients achieving
HbA1c<7.0%. Pooled safety and tolerability data across trials were also analyzed.
RESULTS: Reductions from baseline to week 24 in HbA1c were observed in all
saxagliptin treatment groups versus placebo: saxagliptin 2.5 or 5 mg plus
metformin (mean difference from placebo, -0.87% and -0.89%, respectively),
glyburide (-0.51% and -0.52%), or thiazolidinedione (-0.45% and -0.60%).
Improvement was also observed in FPG and PPG-AUC. Adverse events for the US
cohort were consistent with previously reported data from the 3 trials. The
pooled incidence of reported hypoglycemia was 5.3% and 11.4% with saxagliptin 2.5
and 5 mg/d add-on, respectively, versus 6.8% with placebo add-on.
CONCLUSIONS: This post-hoc analysis in a cohort of US patients with T2DM
uncontrolled on monotherapy suggests that saxagliptin 2.5 or 5 mg as add-on
therapy to OADs results in improvement across key glycemic parameters compared
with placebo add-on and was generally safe and well tolerated.
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