Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial
Aim: To compare the efficacy and safety of sitagliptin vs. glipizide in patients with type 2 diabetes and inadequate glycaemic control [haemoglobin A1c (HbA1c) ≥ 6.5 and ≤10%] on metformin monotherapy. Methods: After a metformin dose titration/stabilization period (≥1500 mg/day), 1172 patients were randomized to the addition of sitagliptin 100 mg q.d. (N = 588) or glipizide 5 mg/day (uptitrated to a potential maximum 20 mg/day) (N =584) for 52 weeks. The primary analysis assessed whether sitagliptin was non-inferior to glipizide regarding HbA1c changes from baseline at Week 52 using a per-protocol approach.
Results: From a mean baseline of 7.5%, HbA1c changes from baseline were =0.67% at Week 52 in both groups, confirming non-inferiority. The proportions achieving an HbA1c < 7% were 63% (sitagliptin) and 59% (glipizide). Fasting plasma glucose changes from baseline were =0.56 mmol/l (=10.0 mg/dl) and =0.42 mmol/l (=7.5 mg/dl) for sitagliptin and glipizide, respectively. The proportion of patients experiencing hypoglycaemia episodes was significantly (p < 0.001) higher with glipizide (32%) than with sitagliptin (5%), with 657 events in glipizide-treated patients compared with 50 events in sitagliptin-treated patients. Sitagliptin led to weight loss (change from baseline = 1.5 kg) compared with weight gain (+1.1 kg) with glipizide [between-treatment difference (95% confidence interval) = – 2.5 kg (-3.1,-2.0); p < 0.001].
Conclusions: In this study, the addition of sitagliptin compared with glipizide provided similar HbA1c-lowering efficacy over 52 weeks in patients on ongoing metformin therapy. Sitagliptin was generally well tolerated, with a lower risk of hypoglycaemia relative to glipizide and with weight loss compared with weight gain with glipizide.
Keywords: dipeptidyl peptidase-IV, DPP-IV, incretins, MK-0431, sulfonylureas Received 24 October 2006; returned for revision 15 December 2006; revised version accepted 18 December 2006