Ultra-rapid-acting insulin analogues(Albireo Pharma, Inc.)

The objective was to evaluate the safety and efficacy of ultra-rapid-acting insulin with the Boost and Ease-off features of the Cambridge hybrid closed-loop system.

A secondary analysis of Boost and Ease-off from two double-blind, randomized, crossover hybrid closed-loop studies comparing (1) Fiasp to insulin aspart (n = 25), and (2) Lyumjev to insulin lispro (n = 26) was carried out. Mean glucose on initialization of Boost and Ease-off, change in glucose 60 and 120 minutes after initialization, duration and frequency of use, mean glucose, and time in, above, and below target glucose range were calculated for periods of Boost use, Ease-off use, or neither.

Participants used Boost for longer with Fiasp than insulin aspart (median [interquartile range, IQR] = 75 [53-125] minutes vs 60 [49-75] minutes; P = .01). Mean glucose on Boost initialization with Fiasp was 238 ± 62 mg/dL compared with 218 ± 45 mg/dL with insulin aspart (P = .08). Fiasp use resulted in a greater glucose reduction 120 minutes after Boost initialization [-59 ± 34 mg/dL vs -43 ± 31 mg/dL; P = .02]. There were no statistically significant differences in sensor glucose endpoints during Boost or Ease-off periods between Fiasp and aspart. There were no statistically significant differences during Boost or Ease-off periods when comparing Lyumjev with insulin lispro. There were no safety issues when using Boost and Ease-off with ultra-rapid insulins.

The use of Fiasp and Lyumjev during Boost or Ease-off resulted in comparable safety and efficacy to using insulin aspart and lispro.

Introduction: This study aimed to compare efficacy and safety of ultra-rapid-acting insulin analogs (URAIs; faster aspart [FAsp], ultra-rapid lispro [URLi], and technosphere insulin [TI]) with rapid-acting insulin analogs (RAI) in individuals with type 1 (T1D) or type 2 diabetes (T2D). Methods: Searching for randomized control trial comparing the effects of URAI versus RAI that lasted at least 12 weeks, we initially selected 15 studies for analysis. Three studies involving TI were excluded due to a high degree of heterogeneity. The final meta-analysis included only 12 studies with either FAsp or URLi. Results: Mealtime URAI significantly reduced overall early 1 h postprandial glycemia in individuals with T1D (-20.230 mg/dL [95% confidence interval, 95% CI -24.040 to -16.421]; P < 0.001; I² = 33.42%) and those with T2D (-9.138 mg/dL [95% CI -12.612 to -5.663]; P < 0.001; I² = 0%). However, the significant reduction in 2 h postprandial glucose remained only in individuals with T1D (-17.620 mg/dL [95% CI -26.047 to -9.193]; P < 0.001; I² = 65.88%). These benefits were lost when URAI was administered postmeal. At 24-26 weeks, there was no significant difference in HbA1c between groups, but at 52 weeks, a slight reduction in HbA1c with mealtime URAI was observed (-0.080% [95% CI -0.147 to -0.013]; P = 0.019; I² = 0%). No difference in weight or the rate of severe or confirmed hypoglycemia was observed. Only individuals with T1D showed a small, but significant increase in early 1-h hypoglycemia with URAI (1.468 [95% CI 1.235 to 1.747]; P < 0.001; I² = 0%). Conclusion: Mealtime URAI improves 1 and 2 h postprandial glycemic control compared to RAI without increasing hypoglycemia or weight gain.