Long-term efficacy and safety of insulin detemir compared to Neutral Protamine Hagedorn insulin in patients with Type 1 diabetes using a treat-to-target basal-bolus regimen with insulin aspart at meals: a 2-year, randomized, controlled trial.
OBJECTIVE
This 24-month, multi-national, open-label, parallel group trial investigated the long-term efficacy and safety of insulin detemir and Neutral Protamine Hagedorn insulin in combination with mealtime insulin aspart in patients with Type 1 diabetes using a treat-to-target concept.


METHODS
Patients were randomized 2 : 1 to detemir (n = 331) or NPH (n = 166) groups. Basal insulin was initiated once daily (evening) and titrated individually based on self-measured plasma glucose (PG) levels, aiming for pre-breakfast and pre-dinner targets < or = 6.0 mmol/l. A second basal morning dose could be added according to pre-defined criteria.


RESULTS
After 24 months, superiority of glycated haemoglobin (HbA(1c)) was achieved with detemir compared to NPH (detemir 7.36%, NPH 7.58%, mean difference -0.22% points) [95% confidence interval (CI) -0.41 to -0.03%], with reductions of 0.94% and 0.72% points, respectively. Fasting PG (FPG(lab)) was also lower with detemir (detemir 8.35 mmol/l, NPH 9.43 mmol/l; P = 0.019). Twenty-two per cent of patients treated with detemir reached an HbA(1c) < or = 7.0% in the absence of confirmed hypoglycaemia during the last month of treatment vs. 13% on NPH (P = 0.019). Risk of major and nocturnal hypoglycaemia was 69% and 46% lower with detemir than with NPH (P < 0.001), respectively; patients treated with detemir gained less weight (detemir 1.7 kg, NPH 2.7 kg; P = 0.024). The overall safety profile was similar in the two groups and treatment with detemir did not result in any unexpected findings.


CONCLUSIONS
Long-term treatment with the insulin analogues detemir + aspart was superior to NPH + aspart in reducing HbA(1c), with added benefits of less major and nocturnal hypoglycaemia and less weight gain.
Bartley
P C
PC
Department of Medicine, University of Queensland, Australia. p.bartley@uq.edu.au
Bogoev
M
M
Larsen
J
J
Philotheou
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology; D000069057:Insulin Detemir; D007336:Insulin, Isophane / Q000627:therapeutic use; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects
D000906:Antibodies; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir; D007336:Insulin, Isophane