PRONTO T1D was a phase 3 study evaluating ultra rapid lispro (URLi) in adults with type 1 diabetes (T1D) for 52 weeks. Subjects were randomized to double-blind mealtime URLi, Humalog, or open-label postmeal URLi with insulin degludec or glargine for the first 26 weeks. Subjects on URLi (n=451) and Humalog (n=442) given 0-2 minutes before meals continued for another 26-weeks to assess long-term safety and efficacy. Mean HbA1c at 52 weeks (7.47% URLi; 7.54% Humalog) increased significantly (p<.001) from baseline in both groups (+0.13% [URLi] vs. +0.20% [Humalog]) and showed an estimated treatment difference (ETD) [95% confidence interval (CI)] (ETD: -0.06 [-0.16, 0.03]) that was similar to that previously reported at 26-weeks. Proportions of patients with HbA1c <7% at Week 52 were similar (URLi, 26.8%; Humalog, 24.5%). At Week 52, self-monitored blood glucose profiles (mg/dL) showed that 1-hour (ETD: -13.5 [-19.4, -7.5]) and 2- hour (ETD: -8.4 [-14.1, -2.7]) postmeal daily mean glucose (and corresponding excursions) as well as the daily mean glucose (ETD: -6.1 [-10.6, -1.6]) were statistically significantly (p<.01) lower during treatment with URLi than Humalog. Mean total insulin dose was 0.80 U/kg (URLi) vs. 0.78 U/kg (Humalog). No difference was observed for body weight change (+0.8 kg [URLi] vs. +0.9 kg [Humalog]; ETD: -0.1 kg [−0.5; 0.4]). Adverse events were similar between URLi and Humalog. No difference was observed for severe hypoglycemia (12.28 events/patient-100yr [URLi] vs. 15.96 [Humalog]) or documented symptomatic hypoglycemia rates (glucose <54 mg/dL) with URLi (4.84 events/patient-year) vs. Humalog (5.18) with a relative rate: 0.93 [95% CI: 0.75;1.16]). No long-term safety issues were identified with URLi. Overall glycemic control and improved postprandial glucose via self-monitoring was maintained after 52 weeks with URLi vs. Humalog suggesting that the efficacy and rapid onset of action of URLi is preserved during long-term treatment in patients with T1D.
L.J. Klaff: Research Support; Self; Abbott, Ascensia Diabetes Care, Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, REMD Biotherapeutics, Roche Diabetes Care, Sanofi-Aventis, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. J. Cho: None. M.A. Dellva: Employee; Self; Eli Lilly and Company. N.C. Schloot: Employee; Self; Lilly Diabetes. J. Tobian: Employee; Self; Eli Lilly and Company. J. Miura: None. D. Dahl: Advisory Panel; Self; Berlin-Chemie AG. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novartis AG, Novo Nordisk A/S. J.M. Bue-Valleskey: Employee; Self; Eli Lilly and Company.
Eli Lilly and Company