Abstract

OBJECTIVE—To compare the effects of monotherapy using nateglinide and the thiazolidinedione troglitazone with initial combination of the two agents on glycated hemoglobin (HbA_1c) in patients with type 2 diabetes inadequately controlled by diet alone.

RESEARCH DESIGN AND METHODS—This study consisted of a 28-week, double-blind, randomized, multicenter study that included a 4-week, single-blind, placebo, run-in period and a 24-week (shortened to 16 weeks), double-blind, active treatment period.

RESULTS—At the 16-week end point, nateglinide 120 mg, troglitazone 600 mg, and the combination of the agents achieved statistically significant decreases in HbA_1c in comparison with placebo and a baseline HbA_1c of 8.1–8.4% (P < 0.001). The reductions in HbA_1c were similar in the nateglinide (0.6%) and troglitazone (0.8%) monotherapy groups. The reduction in HbA_1c (1.7%) was greatest in the combination group; 79% of patients in the combination group achieved HbA_1c levels of <7%. The combination group had a higher number of adverse events, primarily due to an increased incidence of mild hypoglycemia in this treatment group.

CONCLUSIONS—Nateglinide and troglitazone are equally effective in decreasing HbA_1c levels. However, these reductions from baseline HbA_1c values of >8% are not adequate to achieve HbA_1c levels of <7%. In contrast, the combination of nateglinide and of a thiazolidinedione shows an additive effect that is highly effective in reducing HbA_1c levels to the target of <7% in 66% of patients, from a baseline HbA_1c that is just above 8%.