Saxagliptin Added to a Submaximal Dose of Sulphonylurea Improves Glycaemic Control Compared with Uptitration of Sulphonylurea in Patients with Type 2 Diabetes: A Randomised Controlled Trial
Resource
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE v.63 n.9 pp.1395-1406
Journal
International Journal of Clinical Practice
Pages
1395-1406
Date Issued
2009
Date
2009
Author(s)
Chacra, A. R.
Tan, G. H.
Apanovitch, A.
Ravichandran, S.
List, J.
Chen, R.
Abstract
Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy. Methods and patients: A total of 768 patients ( 18-77 years; HbA(1c) screening >= 7.5 to < 10.0%) were randomised and treated with saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg vs. glyburide 10 mg for 24 weeks. Blinded uptitration glyburide was allowed in the glyburide-only arm to a maximum total daily dose of 15 mg. Efficacy analyses were performed using ANCOVA and last- observation- carried-forward methodology. Results: At week 24 , 92% of glyburide-only patients were uptitrated to a total glyburide dose of 15 mg/day. Saxagliptin 2.5 and 5 mg provided statistically significant adjusted mean decreases from baseline to week 24 vs. uptitrated glyburide, respectively, in HbA(1c) (-0.54%, -0.64% vs. +0.08%; both p < 0.0001) and fasting plasma glucose (-7, -10 vs. +1 mg/dl; p = 0.0218 and p = 0.002). The proportion of patients achieving an HbA(1c) < 7% was greater for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide (22.4% and 22.8% vs. 9.1 %; both p < 0.0001). Postprandial glucose area under the curve was reduced for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide (-4296 and -5000 vs . +1196 mg center dot min/dl; both p < 0.0001). Adverse event occurrence was similar across all groups. Reported hypoglycaemic events were not statistically significantly different for saxagliptin 2.5 ( 13.3%) and 5 mg (14.6%) vs. uptitrated glyburide (10.1%). Conclusion: Saxagliptin added to submaximal glyburide therapy led to statistically significant improvements vs. uptitration of glyburide alone across key glycaemic parameters and was generally well tolerated.
Subjects
BETA-CELL APOPTOSIS
EUROPEAN-ASSOCIATION
INSULIN SENSITIVITY
CONSENSUS STATEMENT
THERAPY
METFORMIN
SDGs
Type
journal article