Efficacy and safety of nateglinide plus sitagliptin combination therapy in type 2 diabetes patients inadequately controlled by sitagliptin monotherapy: a phase 3, multicenter, open-label, long-term study

Abstract

Background: Combination therapies of drugs with distinct mechanisms of action are emerging as ways to achieve strict glycemic control, thus preventing the onset and progression of diabetic complications in type 2 diabetes patients. A rapid-acting insulin secretagog, nateglinide, and a potent dipeptidyl peptidase-4 inhibitor, sitagliptin, meet such criteria. Methods: A total of 121 patients inadequately controlled with sitagliptin monotherapy received 52-week combination therapy (nateglinide + sitagliptin). The primary endpoint was the safety of the therapy, and its efficacy was also evaluated. A meal tolerance test was performed 4 weeks before the start of combination therapy (week −4) and at week 24 and week 52 after the start of combination therapy. Results: HbA1c levels were lower at week 52 than at week 0 [−0.42% (95% confidence interval −0.53, −0.31)]. Fasting plasma glucose levels tended to decrease from baseline (week 0) to week 52 [−4.8 mg/dl (−9.4, −0.2)]. In the meal tolerance test, postprandial plasma glucose levels and area under the curve of glucose from before to 2 h after the meal load were lower at week 24 and week 52 than at week −4. In addition, the levels of insulin and active glucagon-like peptide-1 were higher at week 52 than at week −4. Furthermore, the incidence of adverse events in combination therapy with sitagliptin was similar to those previously shown in nateglinide monotherapy. Conclusion: Compared with sitagliptin monotherapy, the combination therapy of nateglinide plus sitagliptin was more effective in type 2 diabetes patients at improving glycemic control while showing similar safety.