Repaglinide versus nateglinide monotherapy: a randomized, multicenter study.
OBJECTIVE
A randomized, parallel-group, open-label, multicenter 16-week clinical trial compared efficacy and safety of repaglinide monotherapy and nateglinide monotherapy in type 2 diabetic patients previously treated with diet and exercise.


METHODS
Enrolled patients (n = 150) had received treatment with diet and exercise in the previous 3 months with HbA(1c) >7 and < or =12%. Patients were randomized to receive monotherapy with repaglinide (n = 76) (0.5 mg/meal, maximum dose 4 mg/meal) or nateglinide (n = 74) (60 mg/meal, maximum dose 120 mg/meal) for 16 weeks. Primary and secondary efficacy end points were changes in HbA(1c) and fasting plasma glucose (FPG) values from baseline, respectively. Postprandial glucose, insulin, and glucagon were assessed after a liquid test meal (baseline, week 16). Safety was assessed by incidence of adverse events or hypoglycemia.


RESULTS
Mean baseline HbA(1c) values were similar in both groups (8.9%). Final HbA(1c) values were lower for repaglinide monotherapy than nateglinide monotherapy (7.3 vs. 7.9%). Mean final reductions of HbA(1c) were significantly greater for repaglinide monotherapy than nateglinide monotherapy (-1.57 vs. -1.04%; P = 0.002). Mean changes in FPG also demonstrated significantly greater efficacy for repaglinide than nateglinide (-57 vs. -18 mg/dl; P < 0.001). HbA(1c) values <7% were achieved by 54% of repaglinide-treated patients versus 42% for nateglinide. Median final doses were 6.0 mg/day for repaglinide and 360 mg/day for nateglinide. There were 7% of subjects treated with repaglinide (five subjects with one episode each) who had minor hypoglycemic episodes (blood glucose <50 mg/dl) versus 0 patients for nateglinide. Mean weight gain at the end of the study was 1.8 kg in the repaglinide group as compared with 0.7 kg for the nateglinide group.


CONCLUSIONS
In patients previously treated with diet and exercise, repaglinide and nateglinide had similar postprandial glycemic effects, but repaglinide monotherapy was significantly more effective than nateglinide monotherapy in reducing HbA(1c) and FPG values after 16 weeks of therapy.
Rosenstock
Julio
J
Dallas Diabetes and Endocrine Center, 7777 Forest Lane, Suite C618, Dallas, TX 75230, USA. juliorosenstock@dallasdiabetes.com
Hassman
David R
DR
Madder
Robert D
RD
Brazinsky
Shari A
SA
Farrell
James
J
Khutoryansky
Naum
N
Hale
Paula M
PM
D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002219:Carbamates / Q000627:therapeutic use*; D003510:Cyclohexanes / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000188:drug therapy* / Q000534:rehabilitation; D003927:Diet, Diabetic; D015444:Exercise; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D013997:Time Factors
D015415:Biomarkers; D002219:Carbamates; D003510:Cyclohexanes; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077715:Nateglinide; D010649:Phenylalanine; D010880:Piperidines; C072379:repaglinide