PRONTO-T2D: ‘Good glycemic control’ with ultra-rapid insulin lispro
medwireNews: People with type 2 diabetes who use ultra-rapid insulin lispro as part of a basal–bolus regimen achieve similar overall glycemic control and better control of postprandial glucose (PPG) excursions compared with those using standard lispro, report the PRONTO-T2D investigators.
Ultra-rapid lispro “is a novel ultra rapid insulin lispro formulation developed to more closely match physiological insulin secretion, with the goal of improving PPG control,” explain Annette Chang (Eli Lilly and Company, Indianapolis, Indiana, USA).
In the phase 3 noninferiority trial, 673 patients with an average diabetes duration of 16.5 years were randomly assigned to receive ultra-rapid or standard lispro U100, given by subcutaneous injection 0–2 min before each meal, following an 8-week lead-in period to optimize basal insulin use in combination with prandial lispro. All patients had previously been treated with a basal–bolus insulin regimen along with up to three oral antidiabetic drugs (OADs); metformin and sodium-glucose cotransporter 2 inhibitors could be continued during the trial but all other OADs were discontinued.
In the whole study population, average glycated hemoglobin (HbA1c) levels improved from 8.30% (67.2 mmol/mol) at study entry to 7.29% (56.2 mmol/mol) after the 8-week lead-in period. After this time, average levels reduced further to 6.92% (52.0 mmol/mol) among the 336 participants in the ultra-rapid lispro arm and 6.86% (51.0 mmol/mol) among the 337 in the standard lispro arm at week 26.
The least squares mean difference in HbA1c change from baseline to week 26 between the two groups was 0.06%, and the upper limit of the 95% confidence intervals met the criteria for noninferiority of ultra-rapid versus standard lispro, report Chang and team in Diabetes Care.
They say that ultra-rapid lispro was significantly better than standard lispro for controlling 1- and 2-hour PPG excursions, with average estimated decreases from baseline to week 26 of 0.77 versus 0.11 mmol/L at 1 hour and 1.06 versus 0.09 mmol/L at 2 hours.
Together, these results indicate that ultra-rapid lispro provides “good glycemic control, with clinically significant reductions in HbA1c,” as well as “superior PPG control over lispro treatment,” write the researchers.
They add that this was achieved “with no statistically or clinically significant differences in the most clinically relevant categories of hypoglycemia.” Indeed, average rates of severe (0.02 vs 0.04 events/patient–year) documented (7.57 vs 7.43 events/ patient–year), and nocturnal (0.68 vs 0.53 events/ patient–year) hypoglycemia were all comparable in the ultra-rapid and standard lispro groups.
The risk for postmeal hypoglycemia 0–4 hours after eating was significantly higher among patients given ultra-rapid versus standard lispro (3.51 vs 2.58 events/ patient–year), but Chang and team say that “the absolute rates were very low, corresponding to less than one additional event per patient–year.”
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