Abstract and Introduction
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 HbA1c from baseline using the per-protocol (PP) population.
Results: For the PP cohort, mean baseline HbA1c was 7.3% in both groups. After 2 years, the least squares (LS) mean change in HbA1c 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 HbA1c 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 HbA1c< 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.
Due to the progressive nature of the disease, over time, patients with type 2 diabetes often require combinations of medications to maintain glycaemic control. 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. 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 HbA1c relative to the addition of rosiglitazone. The previously reported results from the first year of the present study 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
Cite this: Safety and Efficacy of Treatment with Sitagliptin or Glipizide in Patients with Type 2 Diabetes Inadequately Controlled on Metformin: A 2-year Study - Medscape - Mar 01, 2010.