Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone

Abstract

Context: Due to the natural progression of type 2 diabetes (T2D), most patients require combination therapy to maintain glycemic control. Objective: Our objective was to evaluate efficacy and safety of saxagliptin plus thiazolidinedione (TZD) in patients with T2D and inadequate glycemic control on TZD monotherapy. Design: The study was a multicenter, randomized, double-blind, placebo (PBO)-controlled phase 3 trial conducted from March 13, 2006, to October 15, 2007. Setting: Patients were recruited from 172 outpatient centers. Patients: Patients with inadequately controlledT2D[glycosylatedhemoglobin(HbA1c) 7.0-10.5%], 18-77 yr, receiving stable TZD monotherapy (pioglitazone 30 or 45 mg or rosiglitazone 4 or 8 mg) for at least 12 wk before screening were eligible. Interventions: A total of 565 patients were randomized and treated with saxagliptin (2.5 or 5 mg) or PBO, once daily, plus stable TZD dose for 24 wk. Main Outcome Measures: Primaryoutcomewaschange inHbA1c from baseline towk24. Secondary outcomes were change from baseline to wk 24 in fasting plasma glucose, proportion of patients achieving HbA1c less than 7.0%, and postprandial glucose area under the curve. Results: At 24 wk, saxagliptin (2.5 and 5 mg) plus TZD demonstrated statistically significant adjusted mean decreases vs. PBO in HbA1c [-0.66% (P = 0.0007) and -0.94% (P < 0.0001) vs.-0.30%] and fasting plasma glucose[-0.8mmol/liter (P = 0.0053)and -1 mmol/liter(P = 0.0005)vs. -0.2mmol/liter]. Proportion of patients achieving HbA1c less than 7.0% was greater for saxagliptin (2.5 and 5 mg) plus TZD vs. PBO [42.2% (P = 0.001) and 41.8% (P = 0.0013) vs. 25.6%]. Postprandial glucose area under the curve was significantly reduced [-436 mmol • min/liter (saxagliptin 2.5 mg plus TZD) and -514 mmol • min/liter (saxagliptin 5mgplus TZD) vs.-149mmol • min/liter (PBO)]. Saxagliptin was generally well tolerated; adverse event occurrence and reported hypoglycemic events were similar across all groups. Conclusions: Saxagliptin added to TZD provided statistically significant improvements in key parameters of glycemic control vs. TZD monotherapy and was generally well tolerated. Copyright © 2009 by The Endocrine Society.