Reduced hypoglycaemia using liver‐targeted insulin in individuals with type 1 diabetes

Abstract Aim To investigate whether an increased bolus: basal insulin ratio (BBR) with liver‐targeted bolus insulin (BoI) would increase BoI use and decrease hypoglycaemic events (HEv). Patient Population and Methods We enrolled 52 persons (HbA1c 6.9% ± 0.12%, mean ± SEM) with type 1 diabetes using multiple daily injections. Hepatic‐directed vesicle (HDV) was used to deliver 1% of peripheral injected BoI to the liver. A 90‐day run‐in period was used to introduce subjects to unblinded continuous glucose monitoring and optimize standard basal insulin (BaI) (degludec) and BoI (lispro) dosing. At 90 days, BoI was changed to HDV‐insulin lispro and subjects were randomized to an immediate 10% or 40% decrease in BaI dose. Results At 90 days postrandomization, total insulin dosing was increased by ~7% in both cohorts. The −10% and −40% BaI cohorts were on 7.7% and 13% greater BoI with 6.9% and 30% ( P = .02) increases in BBR, respectively. Compared with baseline at randomization, nocturnal level 2 HEv were reduced by 21% and 43%, with 54% and 59% reductions in patient‐reported HEv in the −10% and −40% BaI cohorts, respectively. Conclusions Our study shows that liver‐targeted BoI safely decreases HEv and symptoms without compromising glucose control. We further show that with initiation of liver‐targeted BoI, the BBR can be safely increased by significantly lowering BaI dosing, leading to greater BoI usage.