Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial.
BACKGROUND
Most antidiabetic agents target only 1 of several underlying causes of diabetes. The complementary actions of the antidiabetic agents metformin hydrochloride and rosiglitazone maleate may maintain optimal glycemic control in patients with type 2 diabetes; therefore, their combined use may be indicated for patients whose diabetes is poorly controlled by metformin alone.


OBJECTIVE
To evaluate the efficacy of metformin-rosiglitazone therapy in patients whose type 2 diabetes is inadequately controlled with metformin alone.


METHODS
Randomized, double-blind, placebo-controlled trial from April 1997 and March 1998.


METHODS
Thirty-six outpatient centers in the United States.


METHODS
Three hundred forty-eight patients aged 40 to 80 years with a mean fasting plasma glucose level of 12.0 mmol/L (216 mg/dL), a mean glycosylated hemoglobin level of 8.8%, and a mean body mass index of 30.1 kg/m2 were randomized.


METHODS
Patients were assigned to receive 2.5 g/d of metformin plus placebo (n = 116); 2.5 g/d of metformin plus 4 mg/d of rosiglitazone (n = 119); or 2.5 g/d of metformin and 8 mg/d of rosiglitazone (n = 113) for 26 weeks.


METHODS
Glycosylated hemoglobin levels, fasting plasma glucose levels, insulin sensitivity, and beta-cell function, compared between baseline and week 26, by treatment group.


RESULTS
Glycosylated hemoglobin levels, fasting plasma glucose levels, insulin sensitivity, and beta-cell function improved significantly with metformin-rosiglitazone therapy in a dose-dependent manner. The mean levels of glycosylated hemoglobin decreased by 1.0% in the 4 mg/d metformin-rosiglitazone group and by 1.2% in the 8 mg/d metformin-rosiglitazone group and fasting plasma glucose levels by 2.2 mmol/L (39.8 mg/dL) and 2.9 mmol/L (52.9 mg/dL) compared with the metformin-placebo group (P<.001 for all). Of patients receiving 8 mg/d of metformin-rosiglitazone, 28.1% achieved a glycosylated hemoglobin level of 7% or less [corrected]. Dose-dependent increases in body weight and total and low-density lipoprotein cholesterol levels were observed (P<.001 for both rosiglitazone groups vs placebo). The proportion of patients reporting adverse experiences was comparable across all groups.


CONCLUSIONS
Our data suggest that combination treatment with once-daily metformin-rosiglitazone improves glycemic control, insulin sensitivity, and beta-cell function more effectively than treatment with metformin alone.
Fonseca
V
V
Department of Medicine, Tulane University, New Orleans, LA 70112, USA. vfonseca@mailhost.tcs.tulane.edu
Rosenstock
J
J
Patwardhan
R
R
Salzman
A
A
D000328:Adult; D000368:Aged; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D000077154:Rosiglitazone; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D045162:Thiazolidinediones
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D008687:Metformin; D000077154:Rosiglitazone; D013844:Thiazoles; D045162:Thiazolidinediones