Humulin Insulin: R, N, 70/30, and 50/50

Medical Disclaimer

This article is for informational purposes only and does not constitute medical advice. Always consult your physician or a qualified healthcare provider regarding any medical condition or treatment.

Key Takeaways

  • Humulin is Eli Lilly's family of human insulins, including R (regular), N (NPH), premixed 70/30 and 50/50, and the concentrated U-500 formulation.
  • These older insulins are not analogs but remain widely used because of lower cost, OTC availability in most U.S. states, and Walmart ReliOn private-label distribution.
  • Humulin R and N have less predictable timing than modern analogs, requiring stricter meal timing and a higher hypoglycemia risk profile.
  • Discuss with your prescriber whether Humulin is appropriate for your regimen, especially if cost, insurance gaps, or specific concentration needs apply.

Humulin is Eli Lilly’s brand of human insulin, manufactured by recombinant DNA technology and approved by the FDA in the early 1980s. The family includes Humulin R (regular short-acting), Humulin N (NPH intermediate-acting), Humulin 70/30 and Humulin 50/50 (premixed), and Humulin R U-500 (concentrated for high-dose insulin resistance). Despite the rise of analog insulins, Humulin remains widely used because of lower cost, OTC availability, and Walmart’s ReliOn private-label partnership.

The Humulin Family

Product Type Onset Peak Duration
Humulin R (U-100) Regular short-acting 30 min 2-4 hr 6-8 hr
Humulin N NPH intermediate 1-3 hr 4-12 hr 14-24 hr
Humulin 70/30 70% NPH + 30% Regular 30 min Dual peaks 14-24 hr
Humulin 50/50 50% NPH + 50% Regular 30 min Dual peaks 14-24 hr
Humulin R U-500 Concentrated regular 30 min 4-8 hr 13-24 hr

Humulin R: Regular Short-Acting

Humulin R is unmodified human insulin in U-100 strength. It is given subcutaneously about 30 minutes before meals to cover postprandial glucose rises. Because the timing is less precise than analogs like Humalog, NovoLog, or Lyumjev, people using Humulin R must time meals carefully or risk hypoglycemia.

Humulin R is also approved for intravenous use in hospital settings and is the only human insulin commonly used in IV insulin protocols for diabetic ketoacidosis (DKA) and surgical glucose management.

Humulin N: NPH Intermediate-Acting

Humulin N is NPH (Neutral Protamine Hagedorn) insulin, where protamine extends the duration of regular insulin. The result is a cloudy suspension that must be gently rolled before use to ensure even mixing. NPH has a pronounced peak effect 4-12 hours after injection, which makes timing important to avoid overnight or mid-afternoon hypoglycemia.

NPH is typically given twice daily, sometimes combined with regular insulin at the same injections. It has been largely replaced by long-acting analogs (Lantus, Levemir, Tresiba, Toujeo, Basaglar) in modern T1D and T2D care, but cost and availability still drive NPH use globally.

Humulin 70/30 and 50/50: Premixed

Humulin 70/30 contains 70% NPH and 30% regular insulin in a single vial or pen. Humulin 50/50 is a 50/50 split. These premixed formulations simplify regimens to two daily injections (typically before breakfast and dinner) and are most often used in T2D when a basal-bolus regimen is too complex or costly. The trade-off is rigid meal timing and less flexibility for variable meals.

Humulin R U-500

Humulin R U-500 is regular insulin at five times the standard concentration, delivering 500 units per mL. It is reserved for people with severe insulin resistance — typically those needing more than 200 units of insulin per day. Because of dosing complexity and serious risks of overdose if confused with U-100, U-500 always requires a prescription and is delivered through dedicated U-500 syringes or the Humulin R U-500 KwikPen.

OTC Status and Walmart ReliOn

Humulin R, Humulin N, and Humulin 70/30 are sold over the counter in most U.S. states. The Walmart ReliOn line (manufactured by Novo Nordisk for Walmart) offers Novolin R, N, and 70/30 at roughly $25 per vial — these are not Humulin specifically but are interchangeable human insulins. A few states (Indiana, Maine) require a prescription for all insulin. Always confirm state law and ask the pharmacist before assuming OTC purchase is allowed.

The OTC pathway is most often used by uninsured patients, people in insurance gaps, or those whose insulin pump or pen runs out unexpectedly. It is not a substitute for guided diabetes care.

Side Effects and Risks

  • Hypoglycemia — the most common and dangerous side effect; symptoms include shakiness, sweating, confusion, and loss of consciousness if untreated.
  • Weight gain — often 2-6 kg in the first year of insulin therapy.
  • Injection site reactions — redness, swelling, lipohypertrophy with site reuse.
  • Hypokalemia — insulin shifts potassium into cells; relevant in IV use.
  • Allergic reactions — rare with modern recombinant human insulin.

Where Humulin Fits Today

For people newly diagnosed with insulin-requiring diabetes, modern analogs remain first-line because of better predictability and lower hypoglycemia risk. But Humulin is still the right choice for many — especially people paying cash, those with limited insurance, or patients on long-standing twice-daily premixed regimens that work well for them. People still in the prediabetes range should focus on prevention strategies described in our treatment overview and monitor progress through A1C testing.

The Bottom Line

Humulin insulin is a long-trusted family of human insulins covering the full spectrum from rapid coverage (R) through intermediate basal (N), premixed combinations, and the concentrated U-500. It works less smoothly than modern analogs but costs significantly less and remains OTC in most U.S. states. Always coordinate insulin choice with your diabetes care team and never switch concentrations or formulations without explicit dosing instructions.

Frequently Asked Questions

Is Humulin insulin available over the counter?

Humulin R and Humulin N (and the Walmart ReliOn versions) are available over the counter without a prescription in most U.S. states, except Indiana, Maine, and a few others that require a prescription. The premixed 70/30 versions are similarly available OTC in most states. U-500 always requires a prescription.

How long does Humulin take to start working?

Humulin R (regular) typically starts working in about 30 minutes, peaks at 2-4 hours, and lasts 6-8 hours. Humulin N (NPH) starts in 1-3 hours, peaks at 4-12 hours, and lasts up to 24 hours. Humulin 70/30 combines both profiles. Always inject Humulin R about 30 minutes before meals.

What is the difference between Humulin and Humalog?

Humulin is human insulin produced by recombinant DNA technology. Humalog (insulin lispro) is a rapid-acting insulin analog with a faster onset and shorter duration. Humalog is generally preferred for mealtime control because of more flexible timing, but Humulin remains popular for cost reasons.

Sources

  1. U.S. Food and Drug Administration. Humulin R, Humulin N, Humulin 70/30, Humulin R U-500 Prescribing Information. https://www.accessdata.fda.gov/scripts/cder/daf/
  2. Eli Lilly and Company. Humulin Product Information. https://www.lilly.com/products/humulin
  3. American Diabetes Association. Standards of Care in Diabetes 2024 — Pharmacologic Approaches. Diabetes Care 47(Suppl 1):S158-S178.