Better long-term glycaemic control with the basal insulin glargine as compared with NPH in patients with Type 1 diabetes mellitus given meal-time lispro insulin.
BACKGROUND
Glargine is a long-acting insulin analogue potentially more suitable than NPH insulin in intensive treatment of Type 1 diabetes mellitus (T1 DM), but no study has proven superiority. The aim of this study was to test superiority of glargine on long-term blood glucose (BG) as well as on responses to hypoglycaemia vs. NPH.


METHODS
One hundred and twenty-one patients with T1 DM on intensive therapy on four times/day NPH and lispro insulin at each meal, were randomized to either continuation of NPH four times/day (n = 60), or once daily glargine at dinner-time (n = 61) for 1 year. Lispro insulin at meal-time was continued in both groups. In 11 patients from each group, responses to stepped hyperinsulinaemic-hypoglycaemia were measured before and after 1 year's treatment.


RESULTS
Mean daily BG was lower with glargine [7.6 +/- 0.11 mmol/l (137 +/- 2 mg/dl)] vs. NPH [8.1 +/- 0.22 mmol/l (146 +/- 4 mg/dl)] (P < 0.05). HbA(1c) at 4 months did not change with NPH, but decreased with glargine (from 7.1 +/- 0.1 to 6.7 +/- 0.1%), and remained lower than NPH at 12 months (6.6 +/- 0.1%, P < 0.05 vs. NPH). Frequency of mild hypoglycaemia [self-assisted episodes, blood glucose < or = 4.0 mmol/l (72 mg/dl)] was lower with glargine vs. NPH (7.2 +/- 0.5 and 13.2 +/- 0.6 episodes/patient-month, P < 0.05). After 1 year, NPH treatment resulted in no change of responses to hypoglycaemia, whereas with glargine plasma glucose, thresholds and maximal responses of plasma adrenaline and symptoms to hypoglycaemia improved (P < 0.05).


CONCLUSIONS
The simpler glargine regimen decreases the percentage of HbA(1c) and frequency of hypoglycaemia and improves responses to hypoglycaemia more than NPH. Thus, glargine appears more suitable than NPH as basal insulin for intensive treatment of T1 DM.
Porcellati
F
F
Section of Internal Medicine, Endocrinology and Metabolism, University of Perugia, Via E. Dal Pozzo, I-06126 Perugia, Italy.
Rossetti
P
P
Pampanelli
S
S
Fanelli
C G
CG
Torlone
E
E
Scionti
L
L
Perriello
G
G
Bolli
G B
GB
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015190:Blood Glucose Self-Monitoring; D003071:Cognition / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000069036:Insulin Glargine; D061268:Insulin Lispro; D007336:Insulin, Isophane / Q000009:adverse effects / Q000627:therapeutic use; D049528:Insulin, Long-Acting; D008297:Male
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D061268:Insulin Lispro; D007336:Insulin, Isophane; D049528:Insulin, Long-Acting