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

AIMS: 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 ≤ 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) ≤ 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. Diabet. Med. 25, 442–449 (2008)