Improved glycaemic control with metformin-glibenclamide combined tablet therapy (Glucovance) in Type 2 diabetic patients inadequately controlled on metformin.
OBJECTIVE
To evaluate the efficacy and safety of two dosage strengths of a single-tablet metformin-glibenclamide (glyburide) combination, compared with the respective monotherapies, in patients with Type 2 diabetes mellitus (DM) inadequately controlled by metformin monotherapy.


METHODS
In this 16-week, double-blind, multicentre, parallel-group trial, 411 patients were randomized to receive metformin 500 mg, glibenclamide 5 mg, metformin-glibenclamide 500 mg/2.5 mg or metformin-glibenclamide 500 mg/5 mg, titrated with the intention to achieve fasting plasma glucose (FPG) < or = 7 mmol/l.


RESULTS
Decreases in glycated haemoglobin (HbA1c) and FPG were greater (P < 0.05) for metformin-glibenclamide 500 mg/2.5 mg (-1.20% and -2.62 mmol/l) and 500 mg/5 mg (-0.91% and -2.34 mmol/l), compared with metformin (-0.19% and -0.57 mmol/l) or glibenclamide (-0.33% and -0.73 mmol/l). HbA1c < 7% was achieved by 75% and 64% of patients receiving metformin-glibenclamide 500 mg/2.5 mg and 500 mg/5 mg, respectively, compared with 42% for glibenclamide and 38% for metformin (P = 0.001). These benefits were achieved at lower mean doses of metformin or glibenclamide with metformin-glibenclamide 500 mg/2.5 mg and 500 mg/5 mg (1225 mg/6.1 mg and 1170 mg/11.7 mg) than with glibenclamide (13.4 mg) or metformin (1660 mg). Treatment-related serious adverse events occurred in two patients receiving glibenclamide. Plasma lipid profiles were unaffected and mean changes in body weight were < or = 1.0 kg.


CONCLUSIONS
Intensive management of Type 2 DM with a new metformin-glibenclamide combination tablet improved glycaemic control and facilitated the attainment of glycaemic targets at lower doses of metformin or glibenclamide compared with the respective monotherapies, without compromising tolerability.
Marre
Michel
M
Diabetology-Endocrinology-Metabolism Unit, Hospital of Xavier Bichat, 46 Rue Henri Huchard, 75877 Paris Cedex 18, France.
Howlett
H
H
Lehert
P
P
Allavoine
T
T
D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D019270:Fructosamine / Q000097:blood; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D005905:Glyburide / Q000008:administration & dosage* / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000031:analogs & derivatives* / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000517:prevention & control; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D013607:Tablets; D016896:Treatment Outcome
D001786:Blood Glucose; D004338:Drug Combinations; D019270:Fructosamine; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D008687:Metformin; D013607:Tablets; C025617:glucosylated hemoglobin A