Aims: Insulin lispro protamine suspension (ILPS) and insulin detemir were compared in insulin-naive patients with Type 2 diabetes poorly controlled by oral glucose-lowering agents (OGLAs) to demonstrate non-inferior overall glycaemic control.
Methods: This was a 24-week, multinational, open-label, parallel-group, treat-to-target trial. Adults taking two or more OGLAs were randomized to ILPS (n = 223) or detemir (n = 219) once daily at bedtime. Doses were titrated to target fasting blood glucose (FBG) 5.0-7.2 mmol/l. A pre-breakfast dose was added up to week 8 per prespecified criteria. The primary objective was comparison of glycated haemoglobin (HbA(1c)) change from baseline (non-inferiority margin 0.4%).
Results: At end-point, HbA(1c) decreased from 8.8 +/- 0.7% in both groups to 7.3 +/- 0.9% (ILPS) and 7.5 +/- 1.1% (detemir). Least-squares mean difference (95% confidence interval) for HbA(1c) [-0.21% (-0.39, -0.03)] and glycaemic variability [0.10 mmol/l (-0.02, 0.23)] demonstrated non-inferiority. End-point mean FBG was 7.0 vs. 6.9 mmol/l (P = 0.85), and percentages of patients achieving H < 7.0% were 34.9% vs. 31.2% for ILPS vs. detemir. More ILPS patients used twice-daily dosing (59% vs. 49%). Mean daily insulin dose was 0.39 vs. 0.46 U/kg (P = 0.005) and weight gain was 1.88 vs. 0.36 kg (P < 0.001) for ILPS vs. detemir. Overall hypoglycaemia (episodes patient(-1) year(-1)) (24.2 +/- 33.0 vs. 16.2 +/- 26.1, P = 0.001) and nocturnal (6.3 +/- 12.1 vs. 3.8 +/- 13.2, P < 0.001) rates were higher for ILPS.
Conclusions: At end-point, ILPS was non-inferior to detemir in HbA(1c) change from baseline. Patients using ILPS achieved lower end-point HbA(1c) with lower insulin doses but greater hypoglycaemia and weight gain.
Trial registration: ClinicalTrials.gov NCT00494013.