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

TLDR: The primary aim is to compare the efficacy and safety of sitagliptin vs. glipizide in patients with type 2 diabetes and inadequate glycaemic control on metformin monotherapy.

Abstract: Aim: To compare the efficacy and safety of sitagliptin vs glipizide in patients with type 2 diabetes and inadequate glycaemic control [haemoglobin A1c (HbA1c) ≥ 65 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 qd (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 75%, HbA1c changes from baseline were −067% 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 −056 mmol/l (−100 mg/dl) and −042 mmol/l (−75 mg/dl) for sitagliptin and glipizide, respectively The proportion of patients experiencing hypoglycaemia episodes was significantly (p < 0001) 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 =−15 kg) compared with weight gain (+11 kg) with glipizide [between-treatment difference (95% confidence interval) =−25 kg (−31, −20); p < 0001] 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