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Fonseca V, Rosenstock J, Patwardhan R, Salzman A. Effect of Metformin and Rosiglitazone Combination Therapy in Patients With Type 2 Diabetes Mellitus: A Randomized Controlled Trial. JAMA. 2000;283(13):1695–1702. doi:10.1001/jama.283.13.1695
Author Affiliations: Department of Medicine, Endocrinology Section, Tulane University, New Orleans, La (Dr Fonseca); Dallas Diabetes Center, Dallas, Tex (Dr Rosenstock); Departments of Biometrics (Dr Patwardhan) and Clinical Research and Development (Dr Salzman), SmithKline Beecham Pharmaceuticals, Collegeville, Pa.
Context 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.
Design Randomized, double-blind, placebo-controlled trial from April 1997 and
Setting Thirty-six outpatient centers in the United States.
Patients 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.
Interventions 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.
Main Outcome Measures Glycosylated hemoglobin levels, fasting plasma glucose levels, insulin
sensitivity, and β-cell function, compared between baseline and week
26, by treatment group.
Results Glycosylated hemoglobin levels, fasting plasma glucose levels, insulin
sensitivity, and β-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. 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 β-cell function more
effectively than treatment with metformin alone.
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