Combined bedtime insulin--daytime sulphonylurea regimen compared with two different daily insulin regimens in type 2 diabetes: effects on HbA1c and hypoglycaemia rate--a randomised trial.
BACKGROUND
Several efficacy studies of insulin-therapy regimens in patients with type 2 diabetes mellitus have shown varying results. Moreover, most studies did not address hypoglycaemia frequency and severity.


METHODS
In this multicentre study, we compared the glycaemic efficacy and incidence rate of hypoglycaemic episodes between 3 treatment regimens in obese type 2 diabetic patients with secondary failure to sulphonylurea and metformin. During the run-in phase, patients were treated with glimepiride and metformin. After 3 months, 261 patients with HbA(1c) values >6.5% were randomised to (A) glimepiride + Neutral Protein Hagedorn (NPH) insulin at bedtime, (B) NPH insulin twice daily and (C) 30/70 mixture of short-acting and NPH insulin twice daily. The therapeutic aim was an HbA(1c) level < or =6.5%.


RESULTS
Mean HbA(1c) achieved at 9 months was significantly higher in group A: 8.9% versus 8.3% and 8.4% in groups B and C, respectively (P < 0.001). There was no difference in the mild hypoglycaemic event rate, 0.36 versus 0.48 versus 0.53 events per patient month, in groups A, B and C, respectively. Severe hypoglycaemic events, requiring help from others, did not occur throughout the study. The mean weight gain and insulin dose were comparable in all three groups.


CONCLUSIONS
The glimepiride + NPH insulin treatment resulted in a higher HbA(1c) level, as compared to the other regimens. In the clinical setting of this multicentre study, good glycaemic control was only achieved in a minority of the patients, irrespective of the applied regimen.
Stehouwer
M H A
MH
Research Institute for Endocrinology, Reproduction and Metabolism, VU University Medical Centre, Amsterdam, The Netherlands.
DeVries
J H
JH
Lumeij
J A E
JA
Adèr
H J
HJ
Engbers
A M S
AM
Iperen Av
A van
Av
Snoek
F J
FJ
Heine
R J
RJ
D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007336:Insulin, Isophane / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007336:Insulin, Isophane; D013453:Sulfonylurea Compounds; C057619:glimepiride