In Silico Head-to-Head Comparison of Insulin Glargine 300 U/mL and Insulin Degludec 100 U/mL in Type 1 Diabetes

• Published in: Diabetes technology & therapeutics
• Main Authors: Schiavon, Michele, Visentin, Roberto, Giegerich, Clemens, Sieber, Jochen, Dalla Man, Chiara, Cobelli, Claudio, Klabunde, Thomas
• Format: Journal Article
• Language: English
• Published: United States 01.08.2020
• Subjects: Pharmacodynamics; Mathematical modeling; Basal insulin; Pharmacokinetics; Virtual trial
• ISSN: 1557-8593
• DOI: 10.1089/dia.2020.0027

Second-generation long-acting insulin glargine 300 U/mL (Gla-300) and degludec 100 U/mL (Deg-100) provide novel basal insulin therapies for the treatment of type 1 diabetes (T1D). Both offer a flatter pharmacokinetic (PK) profile than the previous generation of long-acting insulins, thus improving glycemic control while reducing hypoglycemic events. This work describes an head-to-head comparison of the two basal insulins on 24-h glucose profiles and was used to guide the design of a clinical trial. The Universities of Virginia (UVA)/Padova T1D simulator describes the intra-/interday variability of glucose-insulin dynamics and thus provides a robust bench-test for assessing glucose control for basal insulin therapies. A PK model describing subcutaneous absorption of Deg-100, in addition to the one already available for Gla-300, has been developed based on T1D clinical data and incorporated into the simulator. One hundred T1D subjects received a basal insulin dose (Gla-300 or Deg-100) for 12 weeks (8 weeks uptitration, 4 weeks stable dosing) by morning or evening administration in a basal/bolus regimen. The virtual patients were uptitrated to their individual doses with two different titration rules. The last 2-week simulated continuous glucose monitoring data were used to calculate various outcome metrics for both basal insulin treatments, with primary outcome being the percent time in glucose target (70-140 mg/dL). The simulations show no statistically significant difference for Gla-300 versus Deg-100 in the main endpoints. This work suggests comparable glucose control using either Gla-300 or Deg-100 and was used to guide the design of a clinical trial intended to compare second-generation long-acting insulin analogues.