Safety and Efficacy of Treatment with Sitagliptin or Glipizide in Patients with Type 2 Diabetes Inadequately Controlled on Metformin: A 2-year Study

Abstract and Introduction

Abstract

Objectives: To evaluate the 2-year safety and efficacy of adding sitagliptin or glipizide to ongoing metformin in patients with type 2 diabetes.
Methods: Patients who were on a stable dose of metformin (≥ 1500 mg/day) for at least 8 weeks were randomised in a double-blind manner to receive either sitagliptin 100 mg q.d. (N = 588) or glipizide 5 mg/day (up-titrated up to 20 mg/day based upon prespecified glycaemic criteria) (N = 584). The efficacy analysis assessed the change in HbA_1c from baseline using the per-protocol (PP) population.
Results: For the PP cohort, mean baseline HbA_1c was 7.3% in both groups. After 2 years, the least squares (LS) mean change in HbA_1c from baseline [95% confidence interval (CI)] was −0.54% (−0.64, −0.45) with sitagliptin (n = 248) and −0.51% (−0.60, −0.42) with glipizide (n = 256). The rise in HbA_1c from week 24 to week 104 [i.e. coefficient of durability (COD)] was smaller with sitagliptin [COD (95% CI) 0.16%/year (0.10, 0.21)] compared with glipizide [0.26%/year (0.21, 0.31)]. The proportion of patients with an HbA_1c< 7% was 63% and 59% with sitagliptin and glipizide, respectively. The beta-cell responsiveness to a meal challenge was maintained with sitagliptin and decreased with glipizide. The proportion of patients who reported hypoglycaemia was 5% with sitagliptin and 34% with glipizide [difference in proportions (95% CI) = −29% (−33, −25)]. Relative to baseline, sitagliptin was associated with weight loss (−1.6 kg) compared with weight gain (+0.7 kg) with glipizide.
Conclusion: In patients with type 2 diabetes, adding sitagliptin to metformin monotherapy improved glycaemic control over 2 years, similar to the glucose-lowering efficacy observed with adding glipizide, but with greater durability and generally better maintenance of beta-cell function. Sitagliptin was generally well tolerated with a lower risk of hypoglycaemia and weight loss compared with weight gain observed with glipizide.

Introduction

Due to the progressive nature of the disease, over time, patients with type 2 diabetes often require combinations of medications to maintain glycaemic control.^[1] Metformin is the most commonly prescribed oral antihyperglycaemic agent for initial therapy.^[2–4] Incretin-based therapies (e.g. dipeptidyl peptidase-4 (DPP-4) inhibitors and analogues of glucagon-like peptide-1) are newer antihyperglycaemic agents available for the treatment of type 2 diabetes.^[5] In studies of up to 30 weeks, sitagliptin, a DPP-4 inhibitor, added when metformin alone did not provide adequate glycaemic control, significantly improved fasting and postprandial glucose levels and measures of beta-cell function in patients with type 2 diabetes.^[6–8] A previous clinical study showed that the addition of sitagliptin to ongoing metformin therapy provided similar improvement in HbA_1c relative to the addition of rosiglitazone.^[8] The previously reported results from the first year of the present study^[9] showed that compared with the addition of glipizide therapy, the addition of sitagliptin to metformin provided similar glycaemic efficacy with a markedly lower incidence of hypoglycaemia and with weight loss compared with weight gain with the sulfonylurea. While the primary time point for analysis for the present study was at 1 year, the study continued as a randomised, double-blind, active-controlled study for an additional year. The results over the 2-year treatment period are reported herein.

Int J Clin Pract. 2010;65(5):562-576. © 2010  Blackwell Publishing