This phase 3, treat-to-target study evaluated efficacy and safety of URLi vs. lispro in 716 pediatric patients (pts) with type 1 diabetes (T1D) . After 4-week lead-in to optimize basal insulin, pts were randomized to double-blind URLi (n=280) or lispro (n=298) injected 0-2 min prior to meals, or open-label URLi (n=138) injected up to 20 min after meals (URLi+20) . Pts remained on prestudy basal insulin (degludec, detemir, or glargine) . Primary endpoint was HbA1c change from baseline after 26 weeks.
Noninferiority was shown in HbA1c change with URLi vs. lispro: estimated treatment difference (ETD) -0.02% (95% CI -0.17, 0.13) and with URLi+20 vs. lispro: ETD -0.02% (95% CI -0.20, 0.17) . Postprandial glucose (PPG) measured by self-monitored blood glucose (SMBG) was lower with URLi vs. lispro 1 h after breakfast (p<0.001) and dinner (p=0.006) . URLi significantly reduced 1 h postmeal glucose daily mean vs. lispro (p=0.001) . Total daily insulin dose was similar between treatments.
There were no significant differences among treatments in rate or incidence of severe, nocturnal or documented hypoglycemia (<54 mg/dL) . With URLi vs. lispro, rate of postdose hypoglycemia (<54 mg/dL) was higher at ≤2 h (p=0.034) . Incidence of treatment-emergent adverse events was similar between groups. More pts reported an injection site reaction related event with URLi (7.9%) and URLi+20 (2.9%) vs. lispro (2.7%) . All injection site reactions were mild or moderate in severity. Two URLi patients discontinued the study due to injection site reactions.
In children and adolescents with T1D, URLi demonstrated similar overall glycemic control and greater PPG lowering with an acceptable safety and tolerability profile compared with lispro. URLi dosed at the start of meals or up to 20 min after the start of meals showed noninferiority for HbA1c change from baseline vs. lispro. URLi dosed at the beginning of meals showed lower PPG at 1 h after breakfast and dinner and lower 1 h postmeal glucose daily mean vs. lispro.
R. Wadwa: Advisory Panel; Dompé. Consultant; Beta Bionics, Inc. Research Support; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. Other Relationship; Tandem Diabetes Care, Inc. L.M. Laffel: Advisory Panel; Medtronic, Roche Diabetes Care. Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. D.R. Franco: Advisory Panel; Abbott Diabetes, Medtronic, Novo Nordisk, Sanofi. Research Support; Eli Lilly and Company. Speaker's Bureau; Abbott Diabetes, AstraZeneca, Medtronic, Roche Diabetes Care, Sanofi. M.A. Dellva: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. R.K. Pollom: Employee; Eli Lilly and Company.
Eli Lilly and Company