CV181-040 Investigators. 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

Diabetes Center, Federal University of São Paulo, São Paulo, Brazil.
International Journal of Clinical Practice (Impact Factor: 2.57). 07/2009; 63(9):1395-406. DOI: 10.1111/j.1742-1241.2009.02143.x
Source: PubMed


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.
A total of 768 patients (18-77 years; HbA(1c) screening >or= 7.5 to <or= 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.
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.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%).
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.

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Available from: Gerry Tan, Jan 24, 2015
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    • "patients with type 2 diabetes mellitus who received saxagliptin. On the other hand, there are studies that showed a small increase in body weight after treatment with saxagliptin [118] [119]. "
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    ABSTRACT: Currently, obesity and its associated complications are considered major public health problems worldwide. Because the causes are multifactorial and complex, different treatment methods are used, which include diet and exercise, as well as the use of drugs, although they can have adverse side effects. A new target for the treatment of obesity may be the incretin system, which consists of hormones that seem to contribute to weight loss. In this sense, some studies have shown a relationship between weight loss and drugs related to incretin system, including glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. The objective of this review is to summarize the association between the incretin system and obesity treatment. Copyright © 2015. Published by Elsevier Inc.
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    • "DPP-4 inhibitors demonstrate different target mechanisms than sulfonylureas, and combination treatment not only improves glycemic control but minimizes the weaknesses of each drug. Previous studies report the effects of combination treatment without significant increases in the risk of AEs such as hypoglycemia [32, 33]. A recent study reports the efficacy on glucose fluctuation when added to DPP-4 inhibitors and administered to patients receiving ongoing sulfonylurea-based therapy [34]. "
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