Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2-year study

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 mono-therapy 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.