Efficacy and Safety of Ultra-Rapid Lispro in Younger and Older Patients with Type 2 Diabetes: Randomized Double-Blind PRONTO-T2D Study.

INTRODUCTION: Ultra-rapid lispro (URLi) is a new prandial insulin lispro formulation. In the PRONTO-T2D study, URLi, in a basal-bolus regimen with glargine or degludec, was non-inferior to lispro (Humalog® ) for HbA1c reduction and superior for postprandial glucose (PPG) control. We evaluated the efficacy and safety of URLi compared to lispro in younger versus older patients in PRONTO-T2D.

METHODS: PRONTO-T2D was a phase 3, 26-week, double-blind, treat-to-target study in people with type 2 diabetes. In this sub-group analysis, we compared URLi to lispro on the change from baseline  in HbA1c and rate of level 2 hypoglycemia (< 54 mg/dl) in patients aged < 65 (N = 406) and ≥ 65 years (N = 267).

RESULTS: At baseline, patients < 65 versus ≥ 65 years had mean age of 54.9 versus 69.2 years and duration of diabetes 14.6 versus 19.4 years. Mean HbA1c at screening and randomization was 8.35 and 7.34%, respectively, in patients < 65 years, and 8.21 and 7.23%, respectively, in patients ≥ 65 years. At endpoint, mean HbA1c with URLi versus lispro was 6.92 versus 6.90%, respectively, in patients < 65 years and 6.89 versus 6.79%, respectively, in patients ≥ 65 years. URLi significantly reduced 1- and 2-h PPG excursions with a standardized meal test in both age groups: between-treatment differences at 1-h postmeal for younger and older patients was - 9.8 and - 15.1 mg/dl, respectively; and at 2-h postmeal, - 18.7 and - 15.1 mg/dl, respectively, all p < 0.05. Severe and nocturnal hypoglycemia were similar between groups. The relative rate (URLi/Humalog) of level 2 hypoglycemia was lower in older versus younger patients, with a significant treatment-by-age interaction observed. No differential treatment effects were noted for insulin dose, weight, and fasting and maximum glucose after the meal test.

CONCLUSIONS: URLi, in a basal-bolus regimen, resulted in endpoint HbA1c < 7% and significantly lower PPG excursions compared to lispro in both age groups, with reduced level 2 hypoglycemia in older versus younger patients.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT03214380.