Randomized Double-Blind Clinical Trial Comparing Ultra Rapid Lispro with Lispro in a Basal-Bolus Regimen in Patients with Type 2 Diabetes: PRONTO-T2D
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.
RESEARCH DESIGN AND METHODS
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 (n=336) or lispro (n=337) injected 0 to 2 minutes prior to meals. Patients could continue metformin and/or sodium glucose co-transporter-2 inhibitor. The primary end point was change from baseline HbA1c to 26 weeks (noninferiority margin 0.4%), with multiplicity adjusted objectives for postprandial glucose (PPG) excursions during a standardized meal test.
HbA1c 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 HbA1C was -0.38% for URLi and -0.43% for lispro, with an end of treatment HbA1c of 6.92% and 6.86% respectively. URLi was superior to lispro in controlling 1- and 2-h PPG excursions: 1-hour ETD, -0.66 mmol/L (95% CI -1.01, -0.30); 2-hour ETD, -0.96 mmol/L (-1.41, -0.52). Significantly lower PPG excursions were evident from 0.5 to 4 hours postmeal with URLi treatment. There were no significant treatment differences in rates of severe or documented hypoglycemia (<3 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 HbA1c and superior to lispro for PPG control in patients with type 2 diabetes.