NPH insulin (isophane)

also known as: Humulin N, Novolin N, isophane insulin, NPH

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co-crystallized with protamine to produce ~12-hour action; still widely used for cost reasons despite being largely superseded by analog basal insulins for T1DM.

Regular human insulin suspended as a protamine-complexed crystalline formulation (Neutral Protamine Hagedorn — named after its Danish inventor Hans Christian Hagedorn), producing slow dissolution from the SC depot and a ~12-hour duration profile; widely used before the analog era, now mostly relegated to budget-constrained settings and some twice-daily T2DM regimens given its sharp peak and higher hypoglycemia risk vs glargine/degludec.

Mechanism of action

Insulin receptor agonism. Slow dissolution of the protamine-insulin complex from the SC depot produces the intermediate-acting profile. The peak is pronounced (roughly 4–12 hours post-injection), which drives higher nocturnal hypoglycemia risk than modern peakless analogs.

Primary uses

Type 1 diabetes mellitus (basal, twice-daily)
Type 2 diabetes mellitus (basal)
Gestational diabetes (preferred in some pregnancy regimens)

Typical dosing

1–2x daily (subcutaneous)

Fully individualized. Not used IV.

Regulatory status

Approved decades prior to current FDA pathway; commercialized from 1950. Humulin N (Lilly) and Novolin N (Novo Nordisk) are current recombinant versions.

References

[fda-pi] FDA. Humulin N (NPH insulin) prescribing information. Eli Lilly.
[pubmed] Hagedorn HC. "Protamine insulinate." JAMA, 1936;106:177-180.

Related peptides

Regular human insulin

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.

Insulin glargine

The dominant once-daily basal insulin for two decades (Lantus, Sanofi, 2000) — the pI-shift design causes microprecipitation in subcutaneous tissue for a nearly peakless 24-hour absorption profile; Toujeo (U-300) is the same molecule at 3× concentration.

Insulin detemir

Novo Nordisk's fatty-acid-acylated basal insulin (Levemir, 2005) — the myristoyl chain enables reversible albumin binding, extending the half-life; Novo Nordisk announced global discontinuation in December 2023 (US supply ended 2024).

Insulin degludec

Novo Nordisk's ultra-long-acting insulin (Tresiba, 2015) — forms soluble multi-hexamers in SC tissue that slowly dissociate for a >42-hour half-life and a flat, forgiving dosing window; the basal insulin with the lowest hypoglycemia risk profile.

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.