Efficacy of Insulin Lispro Versus Regular Insulin in the Treatment of Hyperkalemia

Introduction: Hyperkalemia is a potential life threatening medical condition, requiring prompt action. IV insulin is used to shift potassium intracellularly but carries a risk of hypoglycemia, especially in those with renal impairment. Rapid-acting insulins like lispro have a shorter half-life compared to regular insulin, which may be beneficial in renal impairment. However, efficacy in treating hyperkalemia is not well established.


Methods: This retrospective, observational non-inferiority study evaluated hyperkalemic patient admitted from 6/1/23 to 12/31/23. Adult patients were included if they were treated for hyperkalemia with either IV lispro or regular insulin, had a baseline blood glucose and a follow-up potassium level within 3 hours post-insulin. Subjects were excluded if they were treated for hyperkalemia within the previous 24 hours, pregnant or incarcerated. Primary objective was to compare the change in potassium between groups within 3 hours of study drug. Secondary objectives included comparing the incidence of hypoglycemia, potassium-lowering effect of low dose insulin in renal impairment, and incidence of cardiac arrest and need for retreatment within 24 hours. Sample size of 501, 1:2 ratio, was required to achieve 80% power using a one-sided two-sample t-test with a non-inferiority margin of 20% and alpha of 0.025.


Results: Total of 501 subjects were included: 335 in the regular group and 166 in the lispro group. Average change in potassium was 1.05 mmol/L (±0.62) in the regular insulin group and 0.95 mmol/L (±0.60) in the lispro group. The difference met non-inferiority, -0.06 mmol/L (95% CI -0.16 to 0.04, p=0.009). Incidence of hypoglycemia in renal impairment was 2.2% in the lispro group and 4.3% in the regular group (p=0.204). Cardiac arrest within 24 hours occurred in 0.6% patient in the lispro group and 1 0.3% patient in the regular group (p=0.149). Retreatment for hyperkalemia was required in 4.2% of the lispro group and 4.5% in the regular group (p=0.893).


Conclusions: Lispro was found to be non-inferior to regular in potassium lowering effects. No statistically significant differences in hypoglycemia, cardiac arrest, or retreatment of hyperkalemia seen. Patients with acute hyperkalemia, IV lispro may be a safe alternative to regular insulin.