PDB6 Indirect Treatment Comparison (ITC) of ULTRA-RAPID Lispro Insulin (URLI) Versus FAST-Acting Insulin Aspart (FASTER ASPART) in Patients with Type 1 Diabetes (T1DM)

Abstract

An ITC was performed to estimate between-treatment differences in the efficacy and safety of URLi and faster aspart in adults with T1DM. A systematic literature search identified randomised controlled trials examining the efficacy and safety of URLi or faster aspart. No head-to-head trials of these insulins were identified. Key trials identified for URLi (PRONTO-T1D; URLi versus insulin lispro) and faster aspart (onset 1 and 8; faster aspart versus insulin aspart), with basal insulin, reported the endpoints (including primary endpoints) at 26 weeks. The Bucher method was used to perform ITC; clinical equivalence was assumed for the insulin lispro and insulin aspart treatment arms (ITC anchor point). ITC endpoints included changes from baseline in HbA1c, post-prandial glucose (PPG) excursions (1 to 4 hours, following a mixed-meal tolerance test), weight, and incidence of severe hypoglycaemia. ITC of URLi versus faster aspart showed a mean difference (MD) of 0.01% (95% confidence interval [CI] -0.09%; 0.11%) for HbA1c change from baseline at 26 weeks; the 95% CI was within the non-inferiority margin (0.4%). Reduction in PPG excursions (mmol/L) were larger with URLi versus faster aspart at all timepoints, statistically significantly greater from 2 hours onwards (MD: 2 hours, -1.22 [-1.93; -0.51] p<0.01; 3 hours, -1.41 [-2.19; -0.64] p<0.01; 4 hours, -0.87 [-1.66; -0.09] p=0.03). No significant between-treatment differences were observed regarding weight increase (treatment difference -0.36 [-0.81; 0.10] kg) or odds and probability of severe hypoglycaemia (odds ratio for URLi versus faster aspart: 1.08 [0.55, 2.12], risk ratio 1.07 [0.57; 2.03]). URLi demonstrated non-inferiority in lowering HbA1c at week 26 and superiority in reducing PPG excursions at 2, 3 and 4 hours versus faster aspart in adults with T1DM. Weight increase and severe hypoglycaemia did not differ significantly between URLi and faster aspart.