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 (5.1 to 74.1 mU/min) in three dosing periods and insulin glargine (20 or 30 mU/m(2)/min) in a fourth period, targeted to achieve 50-100% suppression of EGP. D-[3-(3)H] glucose was infused to assess rates of glucose appearance and disappearance. RESULTS: Mean BIL and insulin glargine concentrations (targeted to reflect the differences in intrinsic affinities of the two basal insulins) ranged from 824 to 11,400 and 212 to 290 pmol/L, respectively, and increased accordingly with increases in dose. Suppression of EGP and stimulation of GDR were observed with increasing concentrations of both insulins. At insulin concentrations where EGP was significantly suppressed, insulin glargine resulted in increased GDR. In contrast, at comparable suppression of EGP, BIL had minimal effect on GDR at lower doses and had substantially less effect on GDR than insulin glargine at higher doses. CONCLUSIONS: The novel basal insulin analog BIL has relative hepatopreferential action and decreased peripheral action, compared with insulin glargine, in healthy subjects.

Remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2, improves serum glucose profiles in type 1 diabetes.

OBJECTIVE: Remogliflozin etabonate (RE), an inhibitor of the sodium-glucose transporter 2, improves glucose profiles in type 2 diabetes. This study assessed safety, tolerability, pharmacokinetics, and pharmacodynamics of RE in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: Ten subjects managed with continuous subcutaneous insulin infusion were enrolled. In addition to basal insulin, subjects received five randomized treatments: placebo, prandial insulin, 50 mg RE, 150 mg RE, and mg RE 500. RESULTS: Adverse events and incidence of hypoglycemia with RE did not differ from placebo and prandial insulin groups. RE significantly increased urine glucose excretion and reduced the rise in plasma glucose concentration after oral glucose. RE reduced incremental adjusted weighted mean glucose (0-4 h) values by 42-49 mg/dL and mean glucose (0-10 h) by 52-69 mg/dL. CONCLUSIONS: RE can be safely administered with insulin in type 1 diabetes and reduces plasma glucose concentrations compared with placebo.