Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.
OBJECTIVE
To compare the effect of repaglinide in combination with metformin with monotherapy of each drug on glycemic control in patients with type 2 diabetes.


METHODS
A total of 83 patients with type 2 diabetes who had inadequate glycemic control (HbA1c > 7.1%) when receiving the antidiabetic agent metformin were enrolled in this multicenter, double-blind trial. Subjects were randomized to continue with their prestudy dose of metformin (n = 27), to continue with their prestudy dose of metformin with the addition of repaglinide (n = 27), or to receive repaglinide alone (n = 29). For patients receiving repaglinide, the optimal dose was determined during a 4- to 8-week titration and continued for a 3-month maintenance period.


RESULTS
In subjects receiving combined therapy, HbA1c was reduced by 1.4 +/- 0.2%, from 8.3 to 6.9% (P = 0.0016) and fasting plasma glucose by 2.2 mmol/l (P = 0.0003). No significant changes were observed in subjects treated with either repaglinide or metformin monotherapy in HbA1c (0.4 and 0.3% decrease, respectively) or fasting plasma glucose (0.5 mmol/l increase and 0.3 mmol/l decrease respectively). Subjects receiving repaglinide either alone or in combination with metformin, had an increase in fasting levels of insulin between baseline and the end of the trial of 4.04 +/- 1.56 and 4.23 +/- 1.50 mU/l, respectively (P < 0.02). Gastrointestinal adverse events were common in the metformin group. An increase in body weight occurred in the repaglinide and combined therapy groups (2.4 +/- 0.5 and 3.0 +/- 0.5 kg, respectively; P < 0.05).


CONCLUSIONS
Combined metformin and repaglinide therapy resulted in superior glycemic control compared with repaglinide or metformin monotherapy in patients with type 2 diabetes whose glycemia had not been well controlled on metformin alone. Repaglinide monotherapy was as effective as metformin monotherapy.
Moses
R
R
Department of Endocrinology, Illawarra Regional Hospital, Wollongong, Australia. robert_moses@uow.edu.au
Slobodniuk
R
R
Boyages
S
S
Colagiuri
S
S
Kidson
W
W
Carter
J
J
Donnelly
T
T
Moffitt
P
P
Hopkins
H
H
D001315:Australia; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D002219:Carbamates / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002096:C-Peptide; D002219:Carbamates; D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D010880:Piperidines; D014280:Triglycerides; C072379:repaglinide