By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The Food and Drug Administration (FDA) has approved a new rapid-acting human insulin analog. Insulin lispro-aabc (ILispro-a) is a novel formulation of insulin lispro that speeds absorption from the subcutaneous injection sites. It will compete with currently available rapid-acting insulin: insulin lispro (Humalog), insulin glulisine (Apidra), insulin aspart (NovoLog), and the “faster” version of insulin aspart (Fiasp). ILispro-a is marketed as Lyumjev.


ILispro-a is indicated to improve glycemic control in adults with diabetes mellitus.1


ILispro-a is given subcutaneously at the start or within 20 minutes after starting a meal.1 Injection sites include the abdomen, upper arm, thigh, or buttocks. The dosage is individualized based on the patient’s metabolic needs, glucose monitoring results, and level of glycemic control.1 ILispro-a is available as 100 units/mL (10 mL vials, 3 mL single-use pens and cartridges) and 200 units/mL (3 mL single-use pens).


ILispro-a is formulated to speed the absorption of insulin lispro from the injection site into the blood stream. The formulation uses a microdose of treprostinil, a prostacyclin analog vasodilator, and sodium citrate that may enhance vascular permeability.2 ILispro-a absorbs faster vs. insulin lispro and insulin aspart, as well as “faster” insulin aspart.3 This corresponded to significant postprandial glucose-lowering vs. insulin-lispro and insulin aspart, but not “faster” insulin aspart.


ILispro-a is not FDA-approved for use in children and is not approved for use in insulin pumps.


The efficacy of ILispro-a was evaluated in a randomized, active-controlled, non-inferiority, 26-week, treat-to-target trial in adult type 1 diabetics (T1D) as well as a study of type 2 diabetics (T2D).1 In the T1D study, subjects were a mean age of 44 years, their mean duration of diabetes was 19 years, 56% were male, 77% were white, and mean body mass index (BMI) was 25.5 kg/m2. Researchers randomized subjects to mealtime ILispro-a (451 subjects), mealtime insulin lispro (442 subjects), or open-label postmeal ILispro-a (329 subjects). Mealtime administration was zero to two minutes before the meal. Postmeal administration was 20 minutes after the start of the meal. All subjects were on basal insulin (either insulin glargine or degludec). The primary endpoint was change from baseline in hemoglobin A1c (HbA1c) at week 26. The inferiority margin was prespecified at 0.4%. At week 26, mealtime ILispro-a showed a mean reduction in HbA1c of 0.12% (baseline, 7.3%) compared to -0.04% for mealtime insulin lispro (baseline, 7.3%), and +0.1% for postmeal ILispro-a (baseline, 7.4%). Both ILispro-a arms met the criteria for noninferiority vs. insulin lispro. In the T2D study, subjects were a mean age of 61 years, 53% were male, 69% were white, their mean disease duration was 17 years, and their BMI was 32.3 kg/m2. Subjects were randomized to mealtime ILispro-a (n = 336) or mealtime lispro (n = 337). At week 26, the mean reduction in HbA1c was -0.36% vs. -0.38%, respectively, from a mean baseline of 7.3%, similarly meeting noninferiority criteria vs. insulin lispro.


The goal for development of rapid-acting insulin analogs is to mimic mealtime endogenous insulin. Insulin lispro was first approved in 1996, followed by insulin aspart (2000), insulin glulisine (2004), and “faster” insulin aspart (2017). The three newer rapid-acting insulins, including ILispro-a, generally feature improved pharmacokinetics (faster onset) and improved pharmacodynamics (better postprandial glucose excursion) vs. the older two, and are significantly faster than subcutaneously human insulin analog.3-5 However, the improved pharmacokinetic (PK) and pharmacodynamics (PD), in general, have not translated into significant improvements in glycemic control (i.e., HbA1c) among the rapid-acting insulins and compared to regular human insulin when these are used with basal insulin.4 In T1D patients, rapid-acting insulin may reduce severe hypoglycemia vs. regular insulin, but less so in T2D patients in whom the incidence generally is much lower.4 ILispro-a is the latest rapid-acting insulin with superior PK/PD characteristics vs. the slowest of the rapid-acting insulin (lispro). However, ILispro-a only showed noninferiority in terms of glycemic control. There is no clinical evidence showing ILispro-a will offer any advantage over the other rapid-acting insulins. The cost for ILispro-a is the same as for insulin lispro and priced at $274.70 for a 10 mL vial (U-100) vs. $284 for insulin glulisine and $289.30 for “faster” insulin aspart.


  1. Eli Lilly. Lyumjev prescribing information. June 2020.
  2. Eli Lilly. A study to evaluate the pharmacokinetics and glucodynamics of LY900014 compared to Humalog in children, adolescents, and adults with type 1 diabetes mellitus. July 18, 2018.
  3. Heise T, Linnebjerg H, Coutant D, et al. Ultrarapid lispro lowers postprandial glucose and more closely matches normal physiological glucose response compared to other rapid insulin analogues: A phase 1 randomized, crossover study. Diabetes Obes Metab 2020; May 21. doi: 10.1111/dom.14094. [Online ahead of print].
  4. Home PD. The pharmacokinetics and pharmacodynamics of rapid-acting insulin analogues and their clinical consequences. Diabetes Obes Metab 2012;14:780-788.
  5. Haahr H, Heise T. Fast-acting insulin aspart: A review of its pharmacokinetic and pharmacodynamic properties and the clinical consequences. Clin Pharmacokinet 2020;59:155-172.