Basal insulin peglispro increases lipid oxidation, metabolic flexibility, thermogenesis and ketone bodies compared to insulin glargine in subjects with type 1 diabetes mellitus.

Aims: When treated with basal insulin peglispro (BIL), patients with type 1 diabetes mellitus (T1DM) exhibit weight loss and lower prandial insulin requirements versus insulin glargine (GL), while total insulin requirements remain similar. One possible explanation is enhanced lipid oxidation and improved ability to switch between glucose and lipid metabolism with BIL. This study compared the effects of BIL and GL on glucose and lipid metabolism in subjects with T1DM.

LY2963016 Insulin Glargine and Insulin Glargine (Lantus) Produce Comparable Pharmacokinetics and Pharmacodynamics at Two Dose Levels.

LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products with identical amino acid sequences. This was a phase 1 single-site, randomized, subject- and investigator-blinded, 4-treatment, 4-period crossover study to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties of LY IGlar and IGlar at 2 different doses. Fasted healthy subjects were randomly assigned to receive 2 single doses of LY IGlar and IGlar (0.

Attenuated suppression of lipolysis explains the increases in triglyceride secretion and concentration associated with basal insulin peglispro relative to insulin glargine treatment in patients with type 1 diabetes.

Aims: To test the hypothesis that, as well as lowering weight and increasing plasma triglyceride (TG) levels and hepatic fat compared with insulin glargine (GL) in patients with type 1 diabetes, the attenuated peripheral effects of basal insulin peglispro (BIL) may include increased free fatty acid flux to the liver, causing increased very-low-density lipoprotein (VLDL)-TG secretion and lipid oxidation, and decreased TG adipose tissue deposition.

Methods: In this open-label, randomized, 2-period crossover study, 14 patients with type 1 diabetes received once-daily, individualized, stable BIL or GL doses for 3 weeks. Palmitate flux was assessed using [9,10- H]palmitate infusion.

Quantification of Basal Insulin Peglispro and Human Insulin in Adipose Tissue Interstitial Fluid by Open-Flow Microperfusion.

Background: Restoration of the physiologic hepatic-to-peripheral insulin gradient may be achieved by either portal vein administration or altering insulin structure to increase hepatic specificity or restrict peripheral access. Basal insulin peglispro (BIL) is a novel, PEGylated basal insulin with a flat pharmacokinetic and glucodynamic profile and altered hepatic-to-peripheral action gradient. We hypothesized reduced BIL exposure in peripheral tissues explains the latter, and in this study assessed the adipose tissue interstitial fluid (ISF) concentrations of BIL compared with human insulin (HI).

Novel hepato-preferential basal insulin peglispro (BIL) does not differentially affect insulin sensitivity compared with insulin glargine in patients with type 1 and type 2 diabetes.

Aims: Basal insulin peglispro (BIL) is a novel PEGylated basal insulin with a flat pharmacokinetic and glucodynamic profile and reduced peripheral effects, which results in a hepato-preferential action. In Phase 3 trials, patients with T1DM treated with BIL had lower prandial insulin requirements, yet improved prandial glucose control, relative to insulin glargine (GL). We hypothesized that this may be because of an enhanced sensitivity to prandial insulin with BIL resulting from lower chronic peripheral insulin action.

Duration of action of two insulin glargine products, LY2963016 insulin glargine and Lantus insulin glargine, in subjects with type 1 diabetes mellitus.

Aims: LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products manufactured by distinct processes, but with identical amino acid sequences. This study compared the duration of action of LY IGlar and IGlar in subjects with type 1 diabetes mellitus (T1DM).

Materials And Methods: This was a randomized, double-blind, single-dose, two-period, crossover study.

Pharmacokinetics of the Long-Acting Basal Insulin LY2605541 in Subjects With Varying Degrees of Renal Function.

The pharmacokinetics of LY2605541 (basal insulin peglispro), a novel long-acting basal insulin analogue, was evaluated in 5 groups of subjects with varying degrees of renal function based on creatinine clearance: normal renal function (>80 mL/min), mild renal impairment (51-80 mL/min), moderate renal impairment (30-50 mL/min), severe renal impairment (<30 mL/min), or end-stage renal disease (ESRD) requiring hemodialysis. Serial blood samples for pharmacokinetic analyses were collected up to 12 days following a single 0.33 U/kg subcutaneous dose of LY2605541.

Comparison of the Pharmacokinetics and Pharmacodynamics of LY2963016 Insulin Glargine and EU- and US-Approved Versions of Lantus Insulin Glargine in Healthy Subjects: Three Randomized Euglycemic Clamp Studies.

Objective: LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products manufactured by distinct processes but with identical amino acid sequences. Three studies evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) similarity of LY IGlar and the European Union- and US-approved versions of IGlar.

Research Design And Methods: These were three single-site, randomized, double-blind, two-treatment, four-period, crossover, euglycemic clamp studies.

Basal insulin peglispro demonstrates preferential hepatic versus peripheral action relative to insulin glargine in healthy subjects.

Objective: We evaluated the endogenous glucose production (EGP) and glucose disposal rate (GDR) over a range of doses of basal insulin peglispro (BIL) and insulin glargine in healthy subjects.

Research Design And Methods: This was a single-center, randomized, open-label, four-period, incomplete-block, crossover study conducted in eight healthy male subjects. Subjects had 8-h euglycemic clamps performed with primed, continuous infusions of BIL (5.