Adding glimepiride to insulin+metformin in type 2 diabetes of more than 10 years' duration--a randomised, double-blind, placebo-controlled, cross-over study.
OBJECTIVE
To investigate the effect on glycaemic control of adding glimepiride to on-going treatment with metformin and insulin in patients with known diabetes more than 10 years.


METHODS
Glimepiride 4 mg or placebo was added in randomised order for three months with a washout period of 6 weeks. All insulin regimens were allowed. Insulin doses were reduced if considered necessary. Continuous glucose monitoring was performed at the end of each period.


RESULTS
Forty-three patients, median age 66 years (46-74), diabetes duration 16 (10-30), BMI 30 kg/m(2) (25-37) and mean HbA1c 7.1% NGSP, (64 mmol/mol IFCC) were randomised. With placebo there was no change in HbA1c while a decrease of 0.6%, (7 mmol/mol IFCC) (P < 0.001), was observed with glimepiride even though insulin doses had to be reduced in 23 patients (median change 29%, range 2-100%). Minor hypoglycaemia was reported but no severe hypoglycaemic event was observed. The ratio between C-peptide/glucose increased significantly (P < 0.001) with glimepiride, both fasting and postprandially and, in a stepwise multiple regression analysis of possible predictive factors for response, a more pronounced decrease in HbA1c was associated with the magnitude of the increment in C-peptide/glucose. Older age was associated with a smaller response. Twenty-nine patients (67%) were defined as responders if this was defined as an HbA1c decrease ≥0.5% (5 mmol/mol IFCC) or an insulin dose reduction ≥20%.


CONCLUSIONS
Even after long duration of diabetes, addition of glimepiride to insulin and metformin can be effective in lowering HbA1c and/or reducing the need for exogenous insulin.
Karolinska Institutet, Department of Clinical Sciences, Division of Medicine, Danderyd Hospital, 182 88 Stockholm, Sweden. Electronic address: asa.nyback-nakell@ds.se.
Å
Å
Nybäck-Nakell
Karolinska Institutet, Department of Clinical Sciences, Division of Medicine, Danderyd Hospital, 182 88 Stockholm, Sweden.
U
U
Adamson
Karolinska Institutet, Department of Clinical Sciences, Division of Medicine, Danderyd Hospital, 182 88 Stockholm, Sweden.
P E
PE
Lins
Karolinska Institutet, Department of Clinical Sciences, Division of Medicine, Danderyd Hospital, 182 88 Stockholm, Sweden.
L
L
Landstedt-Hallin
D000368:Aged; D001786:Blood Glucose; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D019518:Postprandial Period; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; C057619:glimepiride; D008687:Metformin
Combination therapy, C-peptide; Sulphonylureas; Treatment; Type 2 diabetes