Reduced Hypoglycemia Using Liver Targeted Insulin in Persons
In normalcy liver insulinization facilitates glycogen synthesis to minimize hypoglycemia, making the need to insulinize the liver critical for the enhancement of blood glucose control in persons with type 1 diabetes. We hypothesized an increased bolus:basal insulin (BBR) ratio with liver targeted bolus insulin (BoI) would increase BoI use and decrease hypoglycemic events (HEv).

Researchers enrolled 52 persons (A1C 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. Ninety days post-randomization, 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=0.02) increases in BBR, respectively. Compared to 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.

The study demonstrates that liver-targeted BoI safely decreases hypoglycemic events 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.