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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
Author(s) -
Porksen Niels,
Linnebjerg Helle,
Garhyan Parag,
Lam Eric C. Q.,
Knadler Mary P.,
Jacober Scott J.,
Hoevelmann Ulrike,
PlumMoerschel Leona,
Watkins Elaine,
Gastaldelli Amalia,
Heise Tim
Publication year - 2017
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12834
Subject(s) - insulin glargine , basal insulin , type 2 diabetes , insulin , insulin sensitivity , basal (medicine) , medicine , endocrinology , affect (linguistics) , diabetes mellitus , insulin resistance , psychology , communication
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 P hase 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. Materials and methods Two open‐label, randomized, 2‐period crossover clinical studies were conducted in 28 patients with T1DM and 24 patients with T2DM . In each study period, patients received once‐daily, individualized, stable, subcutaneous doses of BIL or GL for 5 weeks before a euglycaemic 2‐step hyperinsulinemic clamp procedure (with [6,6‐ 2 H 2 ]‐glucose in 12 of the patients with T1DM ). M ‐values were derived from the clamp procedure for all patients, with rate of glucose appearance ( Ra ) and disappearance ( Rd ) and insulin sensitivity index ( SI ) determined from the clamps with [6,6‐ 2 H 2 ]‐glucose. Results There were no statistically significant differences between BIL and GL in key measures of hepatic (% Ra suppression during the low‐dose insulin infusion; 78.7% with BIL , 81.8% with GL ) or peripheral ( M ‐value and M / I during the high‐dose insulin infusion, Rd and SI ) insulin sensitivity in patients with T1DM or T2DM . Conclusions The need to reduce prandial insulin observed with BIL during phase 3 trials cannot be explained by the differential effects of BIL and GL on sensitivity to prandial insulin in either T1DM or T2DM .