Randomized Double-Blind Clinical Trial Comparing Ultra Rapid Lispro With Lispro in a Basal-Bolus Regimen in Patients With Type 2 Diabetes: PRONTO-T2D.

Abstract

To evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro in patients with type 2 diabetes on a basal-bolus insulin regimen. This was a phase 3, treat-to-target, double-blind 26-week study. After an 8-week lead-in to optimize basal insulin glargine or degludec in combination with prandial lispro treatment, patients were randomized to blinded URLi (<i>n</i> = 336) or lispro (<i>n</i> = 337) injected 0-2 min prior to meals. Patients could continue metformin and/or a sodium-glucose cotransporter 2 inhibitor. The primary end point was change in HbA_1c from baseline to 26 weeks (noninferiority margin 0.4%), with multiplicity-adjusted objectives for postprandial glucose (PPG) excursions during a standardized meal test. HbA_1c improved for both URLi and lispro, and noninferiority was confirmed: estimated treatment difference (ETD) 0.06% (95% CI -0.05; 0.16). Mean change in HbA_1c was -0.38% for URLi and -0.43% for lispro, with an end-of-treatment HbA_1c of 6.92% and 6.86%, respectively. URLi was superior to lispro in controlling 1- and 2-h PPG excursions: 1-h ETD, -0.66 mmol/L (95% CI -1.01, -0.30); 2-h ETD, -0.96 mmol/L (-1.41, -0.52). Significantly lower PPG excursions were evident from 0.5 to 4.0 h postmeal with URLi treatment. There were no significant treatment differences in rates of severe or documented hypoglycemia (<3.0 mmol/L). Incidence of overall treatment-emergent adverse events was similar between treatments. URLi compared with lispro in a basal-bolus regimen was confirmed to be noninferior for HbA_1c and superior to lispro for PPG control in patients with type 2 diabetes.