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.

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.

• Authors: M A Nauck, G Meininger, D Sheng, L Terranella, P P Stein, Sitagliptin Study 024 Group
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 9 Issue 2 Pg. 194-205 (Mar 2007) ISSN: 1462-8902 [Print] England
• PMID: 17300595 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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