Lipid changes during basal insulin peglispro, insulin glargine, or NPH treatment in six IMAGINE trials

Abstract

Basal insulin peglispro (BIL) is a novel basal insulin with hepato-preferential action resulting from reduced peripheral effects. This report provides an integrated summary of lipid changes at 26 weeks with BIL and comparator insulins (glargine, NPH) from phase III studies in type 1 diabetes (T1D), insulin-naïve patients with type 2 diabetes (T2D), patients with T2D on basal insulin only and patients with T2D on basal-bolus therapy. BIL treatment had little effect on HDL cholesterol and LDL cholesterol in all patients. The effect of both BIL and glargine treatment on triglycerides (TG) depended on whether patients had been previously treated with insulin. When BIL replaced conventional insulin glargine or NPH treatments, increases in TG levels were observed. When BIL or comparator insulins were given for 26 weeks to insulin-naïve patients with T2D, TG levels were unchanged from baseline with BIL but decreased with either glargine or NPH. The decreased peripheral action of BIL may reduce suppression of lipolysis in peripheral adipose tissue resulting in increased free fatty acid delivery to the liver and, hence, increased hepatic TG synthesis and secretion.

The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes

“…Patients treated with glargine had no change in mean LFC, while patients treated with BIL had a mean increase in LFC [LSM difference at 52 weeks: 2.20% (1.26–3.13%); p < 0.001] (Additional file 1: Table S1) [8]. Positive correlations with changes in LFC were found for changes in medium HDL, large VLDL, and VLDL size, but only large VLDL in the glargine group correlated significantly (Table 3).…”

“…Mean LFC did not change in the glargine group, but increased from baseline in the BIL group [LSM difference at 52 weeks: 5.27% (3.43–7.11%); p < 0.001] (Additional file 1: Table S1) [8]. Some correlations were found for changes in lipoprotein parameters with changes in LFC in patients taking BIL (Table 3).…”

“…Data from the Phase 3 clinical program for BIL—compared to insulin glargine or NPH—have also recently been reported [8]. However, the effects of insulin therapies on NMR-determined lipoprotein subclasses is limited to selected cohorts of patients with type 1 diabetes [19–24] and very small studies in type 2 diabetes [25–29].…”

“…In patients previously on basal insulin and randomized to BIL in Phase 2 studies, an increase from baseline in serum TGs was noted [6, 7]. In the Phase 3 program, serial lipid profiles were obtained to further characterize and understand the time course for the potential changes in lipid metabolism in response to BIL [8]. In the overall BIL program at baseline, patients with type 2 diabetes on insulin had nominally lower TG values (mean range 144–149 mg/dL) than insulin naïve patients with type 2 diabetes (mean range 159–161 mg/dL); patients with type 1 diabetes had lower TG values (mean range 83–91 mg/dL) than patients with type 2 diabetes.…”

“…The primary LFC and routine blood lipid results are reported elsewhere [8, 11]. Here we report the results of the lipoprotein particle and related lipid analyses by cohort (type 1 diabetes, type 2 insulin naïve, or type 2 previously on insulin) and treatment (insulin glargine or BIL) at baseline and follow-up.…”