URLi is a novel insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose control. This meta-analysis compared and assessed the consistency of the pharmacokinetics and glucodynamics between URLi and Humalog® in healthy subjects and patients with T1D or T2D. The analysis included 4 randomized, double-blind, crossover, single dose studies healthy subjects (n=74), patients with T1D (n=80), and T2D (n=38), evaluating subcutaneous doses of 7, 15, or 30 U of URLi and Humalog®. An 8 to10-h euglycemic clamp was conducted to assess pharmacodynamics. Meta-analysis showed a ∼5 min faster (95% CI:-5.38, -4.12 min) onset of appearance with URLi vs. Humalog. The early insulin exposure was ∼8 times greater (95% CI:6.63, 8.51) in first 15 min and 3 times greater (95% CI:2.74, 3.22) in the first 30 min after URLi vs. Humalog. URLi reduced the late insulin exposure after 3 hours by 43% (ratio 0.57; 95% CI:0.53, 0.60) and the duration of exposure by 68 min (95% CI:-76.86, -59.53 min) vs. Humalog. URLi had a faster onset of action occurring 10 min earlier (95% CI:-12.01, -8.64 min), and early action was increased 3-fold in the first 30 min (95% CI:2.72, 3.50 min) with URLi vs. Humalog. Late insulin action (glucose infused 4 h to end of the clamp) was reduced by 35% (ratio 0.65; 95% CI:0.61, 0.70) and duration of action was 44 min shorter with URLi (95% CI:-58.60, -29.02 min). Total exposure and glucose infused during the clamp was similar between URLi vs. Humalog across the dose range and in each study population. Across the studied dose range and study populations, URLi consistently had faster absorption, reduced late exposure, and an overall shorter exposure duration compared to Humalog. URLi demonstrated an earlier insulin action while reducing the late insulin action compared to Humalog across the studied dose range and study populations. Disclosure J. Leohr: None. M.A. Dellva: Employee; Self; Eli Lilly and Company. K. Carter: None. E.S. LaBell: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company, Johnson & Johnson, Novartis AG. H. Linnebjerg: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Funding Eli Lilly and Company