A randomized, treat-to-target trial comparing insulin lispro protamine suspension and insulin detemir in insulin-naive patients with Type 2 diabetes.
OBJECTIVE
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.
Fogelfeld
L
L
Stroger Hospital of Cook County and Rush University Medical Center, Chicago, IL, USA.
Dharmalingam
M
M
Robling
K
K
Jones
C
C
Swanson
D
D
Jacober
S
S
D000368:Aged; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069057:Insulin Detemir; D061268:Insulin Lispro; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069057:Insulin Detemir; D061268:Insulin Lispro; D049528:Insulin, Long-Acting