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

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.