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15-06-2022 | Diabetes | News | Article

Liver-targeted insulin reduces hypoglycemic events

Author: Laura Cowen

medwireNews: Switching 1% of standard bolus insulin lispro to a liver-targeted formulation decreases hypoglycemic events without affecting glucose control, OPTI-1 study findings indicate.

“By liver-targeting a fraction of the bolus insulin dose, mealtime insulin can be safely increased, leading to a clinically meaningful increase in the bolus:basal ratio, with a resultant decrease in hypoglycaemic events and symptoms,” write Marc Penn (Summa Health Heart and Vascular Institute, Akron, Ohio, USA) and co-authors in Diabetes, Obesity and Metabolism.

The OPTI-1 study included 57 people using multiple daily insulin injections for type 1 diabetes who had a mean glycated hemoglobin (HbA1c) level between 6.5% (48 mmol/mol) and 8.5% (69 mmol/mol).

They underwent a 12-week run-in period to familiarize them with unblinded continuous glucose monitoring and optimize standard basal insulin (degludec) and bolus insulin (lispro) dosing.

At 12 weeks, insulin lispro was changed to hepatic-directed vesicle (HDV)-insulin lispro and participants were randomly assigned to have their degludec dose reduced by either 10% (n=29) or 40% (n=28) from the last recorded dose during the run-in period.

Penn and team explain that HDV-insulin comprises a novel liver-targeted drug delivery system that “provides more normal insulin biodistribution by mimicking portal vein insulin delivery.” It is administered in a fixed combination of 1% HDV-insulin, 99% unbound insulin.

The researchers hypothesized that lowering basal insulin dose at HDV-lispro initiation “would encourage participants to more aggressively uptitrate bolus HDV-lispro dosing.”

They found that, following randomization, mean daily glucose (MDG) levels increased by 5.6% and 9.5% during the first 6 weeks in the participants who reduced their basal insulin dose by 10% and 40%, respectively. However, by 12 weeks after randomization, the MDG levels had fallen and were similar to those recorded at the end of the run in-period.

During the 12-week postrandomization period, degludec dose increased by 8.8% among the people in the 10% basal reduction cohort and by 3.0% in the 40% basal reduction cohort, with final doses at a mean 0.37 and 0.34 units/kg per day, respectively.

At the end of the study, HDV-lispro bolus doses were a respective 7.7% and 13.0% higher than insulin lispro doses at the end of the run-in period in the 10% and 40% basal reduction cohorts. The corresponding final HDV-lispro bolus doses were a corresponding mean 0.28 and 0.26 units/kg per day.

The final mean total insulin doses of 0.62 and 0.58 units/kg per day in the 10% and 40% basal reduction groups, respectively, represented 6.9% and 7.4% increases compared with the end of the run-in phase.

Overall, the bolus:basal insulin ratio increased by 6.9% in the 10% basal reduction group and by 30.0% in the 40% basal reduction group, a significant difference.

Penn and colleagues also report that although basal, bolus, and total insulin levels all increased, the rates of level 2 nocturnal hypoglycemia were lower at the end of the trial than at randomization, falling by a respective 21% and 43% in the 10% and 40% basal reduction cohorts.

Daytime level 2 hypoglycemic events were unchanged in the 10% basal reduction group but fell by 17% in the 40% reduction cohort, while patient-reported hypoglycemic events fell by a respective 54% and 59%.

HbA1c levels were stable throughout the study period, and the researchers say: “It is remarkable to note that a cohort of participants with an HbA1c of 6.7% was administered 8% more total insulin (13% more bolus insulin) and achieved a near 50% reduction in night-time level 2 hypoglycaemic events by better insulinization of the liver.”

They add: “Whether the increased use of insulin over time will result in greater improvement in blood glucose control needs to be assessed in a study of longer duration.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Diabetes Obes Metab 2022; doi:10.1111/dom.14761

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