Regular human insulin

also known as: Humulin R, Novolin R, Myxredlin, Humulin R U-500

The original recombinant human insulin (Humulin R, 1982) — unmodified native sequence, short-acting kinetics driven by hexamer self-association; U-500 concentration for severely insulin-resistant patients.

Unmodified recombinant human insulin (Humulin R, Lilly, 1982; Novolin R, Novo Nordisk; Myxredlin, Baxter) — the first recombinant protein drug and the reference short-acting insulin against which all rapid-acting analogs are compared; available in standard U-100 concentration and a U-500 concentration (Humulin R U-500, 500 units/mL) for patients requiring >200 units/day.

Mechanism of action

Insulin receptor agonism. The unmodified insulin self-associates into zinc-coordinated hexamers in the vial, and the rate-limiting step after SC injection is hexamer dissociation into absorption-competent monomers — which is why onset is slower and peak is later than rapid-acting analogs.

Primary uses

Type 1 diabetes mellitus (mealtime and IV use)
Type 2 diabetes mellitus
Diabetic ketoacidosis (IV)
Hyperkalemia (IV, with dextrose)
Severe insulin resistance (U-500)

Typical dosing

3x daily before meals (SC) or continuous IV (subcutaneous or IV)

Fully individualized. IV use for DKA, hyperkalemia, or hospital glucose management.

Regulatory status

FDA-approved 1982 as Humulin R (Eli Lilly) — the first recombinant DNA protein drug. Novolin R (Novo Nordisk) followed.

References

[fda-pi] FDA. Humulin R (regular human insulin) prescribing information. Eli Lilly, updated 2023.
[fda-pi] FDA. Humulin R U-500 prescribing information. Eli Lilly.
[pubmed] Johnson IS. "Human insulin from recombinant DNA technology." Science, 1983;219:632-637.

Related peptides

NPH insulin (isophane)

The classical intermediate-acting insulin — regular human insulin co-crystallized with protamine to produce ~12-hour action; still widely used for cost reasons despite being largely superseded by analog basal insulins for T1DM.

Insulin lispro

The first FDA-approved rapid-acting insulin analog (Humalog, Lilly, 1996) — the B28–B29 position swap prevents hexamer self-association, producing faster subcutaneous absorption than regular human insulin.

Insulin aspart

Novo Nordisk's rapid-acting insulin analog (NovoLog / NovoRapid, approved 2000) — the B28 proline → aspartate substitution destabilizes hexamer formation, and the ultra-rapid Fiasp formulation (2017) adds niacinamide and L-arginine for even faster absorption.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.