A comparison of preconstituted, fixed combinations of low-dose glyburide plus metformin versus high-dose glyburide alone in the treatment of type 2 diabetic patients.
In the present study we assessed and compared the effectiveness and safety of preconstituted, fixed, combinations of low-dose glyburide plus metformin with higher-dose glyburide monotherapy in patients with type 2 diabetes. This randomized, double-blind, cross-over study comprised 40 patients. After a 30-day run-in period of dietary treatment, patients received combined glyburide (5, 7.5 or 10 mg/day) and metformin (800, 1,200 or 1,600 mg/day) as preconstitued, fixed combinations, or glyburide alone (5, 10 or 15 mg/day). The dose was increased stepwise so as to have 1 (T1), 2 (T2) and 3 (T3) months of treatment for any given regimen (6 months in total). After 2 weeks of washout (T4), the groups were then crossed over (T5, T6, T7 periods). Body weight, fasting plasma glucose, HbA(1c), blood lactate, total cholesterol and HDL-cholesterol, and triglycerides were measured at the beginning and end of T1 and T5, and end of T2, T3, T6 and T7; postprandial plasma glucose, fasting and postprandial plasma insulin and C-peptide were evaluated at the beginning of T1 and T5, and end of T3 and T7. At these latter time points additional assessments included routine clinical chemistry measurements, ECG, and ophthalmoscopic examination. Statistical analysis was performed by the paired Student's t-test and analysis of variance for cross-over studies. Thirty-three patients completed the study. Fasting plasma glucose, postprandial plasma glucose and HbA(1c) levels improved significantly during combined treatment with glyburide at lower doses plus metformin. This effect was achieved without any major change of insulin and C-peptide concentrations. Circulating lactate concentrations increased during the regimen including metformin, but they remained well within the reference values for normal subjects. Plasma total cholesterol and triglycerides levels remained substantielly unchanged throughout the study, whereas HDL-cholesterol concentrations increased slightly, but significantly, with glyburide plus metformin therapy. Routine clinical chemistry measurements, ECG and ophthalmoscopic examinations did not change during the study. These results demonstrate that improved metabolic control can be achieved with preconstituted, fixed combinations of low-dose glyburide plus metformin in patients with type 2 diabetes, compared to higher doses of the sulphonylurea alone.
Erle
G
G
Division of Endocrine and Metabolic Disease, Diabetes Service, S. Bortolo Hospital, via Rodolfi, I-36100 Vicenza, Italy.
Lovise
S
S
Stocchiero
C
C
Lora
L
L
Coppini
A
A
Marchetti
P
P
Merante
D
D
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004338:Drug Combinations; D005215:Fasting; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D019518:Postprandial Period; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D004338:Drug Combinations; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin