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Summary

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. (= 588) or glipizide 5 mg/day (up-titrated up to 20 mg/day based upon prespecified glycaemic criteria) (= 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 (= 248) and −0.51% (−0.60, −0.42) with glipizide (= 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.