November 05, 2025

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Liver-Targeted Bolus Insulin Therapy Reduces Hypoglycemia Risk In Type 1 Diabetes Patients

Liver-targeted Bolus Insulin Therapy Study

Liver-targeted Bolus Insulin Therapy in Type 1 Diabetes

According to a recent study published in the Diabetes, Obesity and Metabolism, liver-targeted bolus insulin therapy reduces hypoglycemia risk.

Study Overview

A study was conducted 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).

They 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.

Thus, the 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.

Reference

Ruth S. Weinstock et al. Reduced hypoglycaemia using liver-targeted insulin in individuals with type 1 diabetes. First published: 11 May 2022 https://doi.org/10.1111/dom.14761

Keywords

liver‐targeted, bolus, insulin, therapy, type 1, diabetes, reduces, hypoglycemia, risk, Ruth S. Weinstock, Bruce W. Bode, Satish K. Garg, David C. Klonoff, Caroline El Sanadi, W. Blair Geho, Douglas B. Muchmore, Marc S. Penn, Diabetes, Obesity and Metabolism

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