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

Abstract

Aims: 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 >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.

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.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.

Trial registration: ClinicalTrials.gov NCT00313313.

Figure 1

Flow of patients through the study. Recruitment period ran from 17 April 2006 through 2 February 2007, with follow up ending on 14 September 2007. SAXA 2.5 mg + GLY = saxagliptin 2.5 mg/day plus open-label glyburide 7.5 mg/day. SAXA 5 mg + GLY = saxagliptin 5 mg/day plus open-label glyburide 7.5 mg/day. PBO + uptitrated GLY = placebo plus double-blind glyburide 2.5 mg/day and open-label glyburide 7.5 mg/day

Figure 2

Changes in glycaemic variables during 24-week treatment period: saxagliptin + MET vs. monotherapy. (A) HbA_1c adjusted mean change from baseline to week 24. (B) HbA_1c mean change from baseline during 24-week treatment period. (C) Fasting plasma glucose (FPG) adjusted mean change from baseline to week 24. (D) FPG mean change from baseline during 24-week treatment period. Open bars (A and C) and open squares (B and D), saxagliptin 2.5 mg + GLY; grey bars (A and C), and open circles (B and D), saxagliptin 5 mg + GLY; dark grey bars (A and C) and shaded circles (B and D), placebo + UPGLY. ^ap < 0.0001; ^bp = 0.0218; ^cp = 0.0020

Figure 3

Postprandial glucose response to 3-h OGTT: baseline vs. week 24. Black line with squares, baseline values at 0, +30, +60, +120 and +180-min time points; grey line with squares, week 24 values at 0, +30, +60, +120 and +180-min time points. ^aSample size at 120-min time point; ^badjusted mean change in 120-min PPG