Combination therapy with nateglinide and a thiazolidinedione improves glycemic control in type 2 diabetes.
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.


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%.
Dallas Diabetes and Endocrine Center, Dallas, Texas, USA.
Julio
J
Rosenstock
Sharen G
SG
Shen
Marjorie R
MR
Gatlin
James E
JE
Foley
D000328:Adult; D000368:Aged; D003510:Cyclohexanes / Q000008:administration & dosage* / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D045162:Thiazolidinediones; D016896:Treatment Outcome
D003510:Cyclohexanes; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077715:Nateglinide; D010649:Phenylalanine; D013844:Thiazoles; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione