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

Diabetes Obes Metab. 2007 Mar;9(2):194-205. doi: 10.1111/j.1463-1326.2006.00704.x.

Abstract

Aim: To compare the efficacy and safety of sitagliptin vs. glipizide in patients with type 2 diabetes and inadequate glycaemic control [haemoglobin A(1c) (HbA(1c)) > or = 6.5 and < or = 10%] on metformin monotherapy.

Methods: After a metformin dose titration/stabilization period (> or = 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 HbA(1c) changes from baseline at Week 52 using a per-protocol approach.

Results: From a mean baseline of 7.5%, HbA(1c) changes from baseline were -0.67% at Week 52 in both groups, confirming non-inferiority. The proportions achieving an HbA(1c) < 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 HbA(1c)-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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl Peptidase 4
  • Dipeptidyl-Peptidase IV Inhibitors
  • Double-Blind Method
  • Female
  • Glipizide / adverse effects
  • Glipizide / therapeutic use*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use*
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Sitagliptin Phosphate
  • Treatment Outcome
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Protease Inhibitors
  • Pyrazines
  • Triazoles
  • hemoglobin A1c protein, human
  • Metformin
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Sitagliptin Phosphate
  • Glipizide