Comparison of Single-Dose Intravenous Insulin Regular vs. Insulin Lispro for Hyperkalemia Treatment in the Emergency Department: The SIR-LISPRO Trial

Am J Emerg Med. 2026 Mar:101:92-98. doi: 10.1016/j.ajem.2025.12.031. Epub 2025 Dec 26.

Abstract

Introduction: Hyperkalemia is a potentially life-threatening electrolyte disturbance that is present in 2 % to 3 % of emergency department (ED) patient admissions. These patients are commonly treated with intravenous (IV) insulin. Standard of care consists of administering IV insulin regular, but other insulin formulations might be safer and/or more effective, however this has yet to be explored.

Objective: To evaluate the safety and effectiveness of insulin lispro and insulin regular administered intravenously for the treatment of hyperkalemia in ED patients.

Methods: This was a retrospective cohort study that investigated adults that were admitted to the ED of two academic centers and treated for hyperkalemia with 5 units of IV insulin therapy from January 1, 2022, through January 1, 2023. The primary outcome was the change in serum potassium within 6 h following IV insulin regular compared to IV insulin lispro. The primary safety outcome was the proportion of patients who had a hypoglycemic event (blood glucose <70 mg/dl) or required supplemental dextrose administration within 6 h post-insulin administration. Demographic, clinical characteristics, clinical management, and the outcome of change in potassium were associated using linear regression. Dichotomous outcomes pertaining to hypoglycemia were estimated using logistic regression.

Results: Among the 237 patients who met inclusion criteria, 129 received insulin regular, and 108 patients received insulin lispro. We observed a larger decrease in potassium in those that received insulin lispro compared to those that received insulin regular (uMD: -0.24; 95 %CI: -0.42, -0.06). The odds of hypoglycemia were greater among those who received insulin lispro (16 %) compared to insulin regular (7 %) (uOR: 2.49; 95 %CI: 1.08, 6.09).

Conclusions: Intravenous insulin lispro resulted in a statistically significant reduction of serum potassium but resulted in a higher likelihood of hypoglycemia compared to IV insulin regular. Further prospective, controlled studies are needed to assess the clinical significance of the differences between insulin formulations.

Keywords: Hyperkalemia; Hypoglycemia; Insulin.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Emergency Service, Hospital
  • Female
  • Humans
  • Hyperkalemia* / blood
  • Hyperkalemia* / drug therapy
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / therapeutic use
  • Insulin Lispro* / administration & dosage
  • Insulin Lispro* / therapeutic use
  • Insulin* / administration & dosage
  • Male
  • Middle Aged
  • Potassium / blood
  • Retrospective Studies

Substances

  • Insulin Lispro
  • Insulin
  • Hypoglycemic Agents
  • Potassium