Effect of stratification factors and baseline postprandial glucose on glycemic control after treatment with ultra rapid lispro or Humalog: subgroup analyses of PRONTO-T1D

Background and aims Ultra rapid lispro (URLi) is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose (PPG) control. In PRONTO-T1 D, a phase 3, 26-week, treat-to-target study comparing URLi to Humalog in patients with type 1 diabetes (T1D) on a multiple daily injection regimen with insulin glargine or degludec, mealtime URLi was non-inferior to mealtime Humalog for change from baseline HbA1c and superior for PPG control with a similar safety profile to Humalog. Randomization to treatment was stratified by basal insulin type, baseline HbA1c and prandial insulin dosing plan (carb counting, yes / no).

Materials and methods The impact of these randomization strata and baseline 2-hour PPG subgroup on the differential treatment effects of URLi vs Humalog on HbA1c change, insulin dose, and hypoglycaemia rates was assessed from the double-blind treatment groups: mealtime URLi (n = 451) and mealtime Humalog (n = 442).

Results None of the treatment-subgroup interactions were significant (all p > 0.1). However, significant treatment differences (p < 0.05 for URLi vs. Humalog) were associated with basal insulin type for total daily dose estimated treatment difference (ETD) (Degludec: 0.04 U / kg, p = 0.046), and with baseline 2-hour PPG for both HbA1c ETD (> 180 mg / dL: -1.5mmol/mol, p = 0.006) and documented hypoglycemia rate ratio (≤180mg / dL: 0.68, p = 0.026).

Conclusion Numerically, results suggest that basal insulin type, starting PPG, and starting HbA1c, but not prandial dosing plan, may influence the magnitude of the HbA1c improvement and / or hypoglycaemia risk reduction among patients treated with URLi compared to Humalog.

Interessenskonflikt

Disclosures: Jang Ik Cho, Thomas Hardy and Juliana Bue-Valleskey are employees and minor stockholders of Eli Lilly and Company.

Sven Goergens is employee of Lilly Deutschland GmbH and minor stockholder.

Publication History

Article published online:
06 May 2021