Protamine-based insulin non-inferior to detemir for glycemic control
MedWire News: A novel insulin formulation, insulin lispro protamine suspension (ILPS), is non-inferior to insulin detemir for improving glycemic control in patients with Type 2 diabetes that is poorly controlled on oral hypoglycemic drugs, a randomized trial has shown.
But the study, which is published in the journal Diabetic Medicine, also found that twice-daily ILPS was associated with increased weight gain and greater hypoglycemia, suggesting it should only be administered on a once-daily schedule.
The research was undertaken to investigate the efficacy and safety of ILPS, that has a similar 24-hour duration of action to the basal insulins detemir and glargine. While glargine is mainly used once-daily, both ILPS and detemir are considered suitable for once- or twice-daily dosing.
Scott Jacober (Eli Lilly and Company, Indianapolis, Indiana, USA) and team recruited 442 adults with Type 2 diabetes into a 24-week, multinational, open-label, parallel-group, treat-to-target trial. All participants were insulin-naïve and had a glycated hemoglobin (HbA1c) level in the range 7.5–10% despite taking at least two oral glucose-lowering agents.
They were randomly assigned to take either ILPS or insulin detemir once-daily at bedtime, with the doses titrated over the study period to attain a target fasting blood glucose (FBG) of 5.0–7.2 mmol/l. A pre-breakfast dose was added if FBG targets had not been achieved by week 8.
HbA1c fell from 8.8% at baseline to 7.3% with ILPS and 7.5% with insulin detemir at week 24; this result demonstrated statistical non-inferiority between the two treatments for the primary endpoint, write Jacober et al.
ILPS was also non-inferior to insulin detemir for the secondary endpoints of glycemic variability, mean FBG, and the percentage of patients achieving an HbA1c below 7.0%.
However, patients in the ILPS group were more likely to need twice-daily dosing, while weight gain and rates of overall and nocturnal hypoglycemia were significantly higher with ILPS versus detemir.
“Therefore, addition of second injection of ILPS to improve glucose control may result in increased risk of hypoglycemia,” the authors caution.
Jacober et al also observe that insulin detemir did not produce comparable improvements in glycemic control to ILPS despite the use of higher doses. “This suggests that insulin detemir is less potent than ILPS… and corroborates the significantly reduced glycemic-lowering action of insulin detemir compared with ILPS,” they write.
This is a “significant consideration for health economic evaluations,” the team remarks.
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By Joanna Lyford