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FDA Approved Metabolic & Weight Loss

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co-crystallized with protamine to produce ~12-hour action; still widely used for cost reasons despite being largely superseded by analog basal insulins for T1DM.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

  1. [fda-pi] FDA. Humulin N (NPH insulin) prescribing information. Eli Lilly.
  2. [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.

Guides & tools

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.