Adjusting Therapy Profiles When Switching to Ultra-Rapid Lispro in an Advanced Hybrid Closed-Loop System: An in Silico Study

Background: It has been shown that insulin acceleration by itself might not be sufficient to see clear improvements in glycemic metrics, and insulin therapy may need to be adjusted to fully leverage the extra safety margin provided by faster pharmacokinetic (PK) and pharmacodynamic (PD) profiles. The objective of this work is to explore how to perform such adjustments on a commercially available automated insulin delivery (AID) system. Methods: Ultra-rapid lispro (URLi) is modeled within the UVA/Padova simulation platform using data from previously published clamp studies. The Control-IQ AID algorithm is selected as it leverages carbohydrate-to-insulin ratio (CR in g/U), correction factor (CF in mg/dL/U), and basal rate (BR in U/h) daily profiles that are fully customizable. An experiment roadmap is proposed to understand how to safely modify these profiles when switching from lispro to URLi. Results: Simulations show that a 7% decrease in CR (approximately an 8% increase in prandial insulin) and a 7.5% increase in BR lead to cumulative improvements in glucose control with URLi. Comparing with baseline metrics using lispro, a clinically significant increase in time in the range of 70 to 180 mg/dL (overall: 70.2%-75.2%, P < .001; 6 am-12 am: 62.4%-68.5%, P < .001) and a reduction in time below 70 mg/dL (overall: 1.8%-1.2%, P < .001; 6 am-12 am: 1.8%-1.3%, P < .001) were observed. Conclusion: Properly adjusting therapy parameters allows to fully leverage glucose control benefits provided by faster insulin analogues, opening opportunities to take another step forward into a next generation of more effective AID solutions.