Ultra fast-acting insulin lispro biosimilar(Perosphere, Inc.)

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.

This phase 1, randomized, one-day, five-period crossover study in adults with type 1 diabetes on continuous subcutaneous insulin infusion investigated local infusion site pain following infusion of the excipients of ultra rapid lispro (URLi; without insulin) across infusion sites and depths.

Forty participants (mean age, 40.5 years; body mass index [BMI], 27.5) were randomized to one of five infusion site sequences consisting of the arm, thigh, buttock (6 mm cannula depth), and abdomen (6 and 9 mm depth). Basal infusion of sodium citrate and treprostinil in diluent with magnesium chloride was initiated (10 μL/h) and at three, six, and nine hours after basal initiation, 15 unit-equivalent boluses (150 μL) were given. Participants rated their pain on a 0 to 100 mm validated visual analog scale (VAS) at 5 minutes pre-bolus and 1 and 15 minutes post-bolus.

At one minute post-bolus, increased VAS scores were occasionally reported. Most one minute post-bolus scores were ≤10 mm (little to no discomfort) while 7 of 577 were >45 mm (generally considered clinically meaningful pain). Painful infusions were reported more frequently for the arm, and mean VAS scores were higher for the arm compared with the thigh and abdomen. The VAS score distributions were similar between cannula depths. By 15 minutes post-bolus, VAS scores returned to pre-bolus levels.

Local infusion site discomfort after infusion of URLi excipients was reported by a small subset of participants; it was transient, tolerable, and dependent on infusion site but not infusion depth. Given differences within individuals, patients may consider using a different infusion site if they experience discomfort.

NCT05067270.