Basal Insulin Peglispro Tops Insulin Glargine in Three Phase III Trials
Regulatory submission scheduled for early 2015
Positive results have been reported from three completed phase III trials of the investigational basal insulin peglispro (Lilly) in patients with type 2 diabetes.
IMAGINE-2 was a 52-week, phase III, randomized, double-blind study of basal insulin peglispro (n = 1,003) compared with insulin glargine (n = 535) in insulin-naive patients with type 2 diabetes. The insulin therapy was taken alone or on a background of oral antihyperglycemic medication. A subset of patients is continuing in this study until 78 weeks of treatment.
IMAGINE-4 was a 26-week, phase III, randomized, double-blind study designed to compare basal insulin peglispro (n = 691) with insulin glargine (n = 678) in combination with mealtime insulin in patients with type 2 diabetes.
IMAGINE-5 was a 52-week, phase III, open-label study designed to evaluate basal insulin peglispro (n = 307) compared with insulin glargine (n = 159) in patients with type 2 diabetes already taking basal insulin. The study insulin was administered alone or in combination with oral antihyperglycemic medications.
The primary efficacy endpoint of a non-inferior reduction in hemoglobin A1c (HbA1c) compared with insulin glargine was met in all three studies. Having met the primary endpoint, the superiority for HbA1c lowering was examined and, in all three trials, basal insulin peglispro showed a statistically superior reduction in HbA1c compared with insulin glargine.
Peglispro is being studied as a once-daily treatment for both type 1 and type 2 diabetes.
The phase III trials evaluated three specific populations of patients with type 2 diabetes: those who were not previously taking insulin (IMAGINE-2); those taking basal insulin with mealtime insulin (IMAGINE-4); and those currently taking basal insulin (IMAGINE-5). All three studies compared peglispro, an investigational basal insulin, with insulin glargine.These clinical studies also evaluated the secondary endpoints of nocturnal hypoglycemia rates and changes in weight. In all three trials, patients taking basal insulin peglispro experienced significantly lower rates of nocturnal hypoglycemia than those taking insulin glargine. In addition, patients taking peglispro had comparable to significantly less weight gain.
In all three clinical studies, patients taking peglispro showed a small but statistically significant increase in triglycerides. In IMAGINE-4 and IMAGINE-5, there was a corresponding small but statistically significant reduction in high-density lipoprotein cholesterol in the peglispro group compared with those taking insulin glargine; this was not observed in the IMAGINE-2 trial. In IMAGINE-2 and IMAGINE-4, changes in low-density lipoprotein (LDL) cholesterol were not significantly different in patients taking basal insulin peglispro compared with those taking insulin glargine. In the IMAGINE-5 trial, LDL levels were significantly decreased at 52 weeks in peglispro-treated patients compared with those taking insulin glargine.
In an analysis across clinical trials completed to date in patients with type 2 diabetes, the rates of adverse cardiovascular events among patients taking peglispro and those taking insulin glargine were similar, with the upper limit of the 95% confidence interval below 1.8.
In all three clinical trials, more patients taking basal insulin peglispro showed an increase in the liver enzyme alanine aminotransferase (ALT) to greater than three times the upper limit of the normal range compared with those taking insulin glargine. No cases of severe drug-induced liver injury (Hy’s law) occurred in these studies.
In IMAGINE-2 and IMAGINE-5, liver fat was measured using magnetic resonance imaging (MRI) in a subset of patients. In the clinical trial of insulin-naive patients with type 2 diabetes (IMAGINE-2), liver fat in patients treated with peglispro did not change from baseline, whereas patients taking insulin glargine experienced a decrease in liver fat from baseline. In the clinical trial of patients with type 2 diabetes who were already taking basal insulin (IMAGINE-5), patients taking peglispro experienced an increase in liver fat from baseline that stabilized after 26 weeks. Liver fat levels did not change in patients taking insulin glargine during the study.
Source: Lilly; May 12, 2014.