Humulin R is regular human insulin — a short-acting insulin used for mealtime dosing, intravenous infusions in hospitals, diabetic ketoacidosis treatment, and severe hyperkalemia. It has onset in 30 minutes, peak at 2 to 4 hours, and duration of 5 to 8 hours, so it is injected 30 minutes before meals. A concentrated U-500 formulation exists for severe insulin resistance. For routine outpatient mealtime use, modern rapid-acting analogs are usually preferred, but Humulin R remains essential in hospital and emergency settings.
What Humulin R Is
Humulin R is the brand name for regular human insulin, manufactured by Eli Lilly. It is biosynthetic human insulin produced by recombinant DNA technology — identical in structure to the insulin naturally produced by the human pancreas. The “R” stands for “regular,” meaning the insulin is in its standard short-acting form without modification or addition of protamine.
Humulin R is supplied in:
- 10 mL U-100 vials (100 units per mL — standard concentration)
- 20 mL U-500 vials (500 units per mL — concentrated, for severe insulin resistance)
- 3 mL U-500 KwikPens (dedicated pen for U-500 insulin)
How Humulin R Works
Regular human insulin in solution exists primarily as hexamers (six-molecule clusters). Before absorption into the bloodstream, the hexamers must dissociate into dimers and then monomers. This process takes time, which is why regular insulin has a slower onset than rapid-acting analogs designed to dissociate more quickly.
Once in the bloodstream, regular insulin binds to insulin receptors on liver, muscle, and fat cells with the same affinity as native insulin, lowering blood glucose by suppressing liver glucose production and promoting glucose uptake by tissues.
Pharmacokinetics: Onset, Peak, Duration
| Parameter | Humulin R U-100 | Humulin R U-500 |
|---|---|---|
| Onset of action | 30 minutes | 30 minutes |
| Peak effect | 2 to 4 hours | 4 to 8 hours |
| Duration of action | 5 to 8 hours | 13 to 24 hours |
| Concentration | 100 units/mL | 500 units/mL |
| Recommended timing | 30 minutes before meals | 30 minutes before meals (2 to 3 times daily) |
Who Humulin R Is For
- Hospitalized patients needing intravenous insulin (DKA, HHS, ICU hyperglycemia, perioperative glucose control)
- Outpatients needing mealtime insulin who cannot access or afford rapid-acting analogs
- People with severe insulin resistance needing very high doses (U-500 formulation)
- Patients in emergency departments with severe hyperkalemia (IV insulin plus dextrose drives potassium into cells)
- Patients with type 1 or type 2 diabetes on sliding-scale insulin protocols
- Pregnant patients in select situations (regular insulin has long pregnancy safety record)
How Humulin R Is Used
- Inject subcutaneously into the abdomen, thigh, or upper arm using a U-100 syringe or KwikPen
- Inject 30 minutes before a meal to allow time for onset
- For U-500: use only a dedicated U-500 syringe or U-500 KwikPen — never a standard U-100 syringe
- In hospitals: diluted and infused intravenously per institutional protocols
- For sliding scale: dose adjusted based on pre-meal glucose readings according to a prescriber-set scale
Dose, timing, and any sliding-scale protocol are individualized by the prescriber.
Humulin R vs Rapid-Acting Analogs
| Insulin | Onset | Peak | Duration | Pre-meal Timing |
|---|---|---|---|---|
| Humulin R (regular) | 30 min | 2 to 4 hr | 5 to 8 hr | 30 min before |
| Novolog (aspart) | 5 to 15 min | 30 to 90 min | 3 to 5 hr | 5 to 10 min before |
| Humalog (lispro) | 5 to 15 min | 30 to 90 min | 3 to 5 hr | 5 to 15 min before |
| Apidra (glulisine) | 10 to 15 min | 60 to 90 min | 3 to 4 hr | 15 min before |
| Fiasp (faster aspart) | ~2 to 5 min | ~60 min | 3 to 5 hr | At start of meal |
Specific Use Cases
Intravenous Insulin in Hospitals
Regular human insulin is the only insulin FDA-approved for intravenous use. Hospital intensive care units, surgical recovery, and DKA management protocols rely on IV regular insulin drips for tight glucose control. Once IV insulin is converted to subcutaneous before hospital discharge, the patient is usually transitioned to long-acting and rapid-acting analogs.
Diabetic Ketoacidosis (DKA)
Standard DKA treatment uses continuous IV regular insulin (0.1 unit/kg/hour, after fluids and electrolyte correction) to drive blood glucose down gradually, suppress ketogenesis, and reverse acidosis. No other insulin is approved for this use.
Hyperkalemia Treatment
In emergency departments, IV regular insulin combined with intravenous dextrose drives potassium into cells, rapidly lowering dangerously high blood potassium levels. This is a temporizing measure while underlying causes are addressed.
U-500 for Severe Insulin Resistance
Patients with severe insulin resistance (often type 2 diabetes with metabolic syndrome, sometimes lipodystrophy syndromes) may require more than 200 units of insulin per day — too much volume for comfortable injection with U-100. Humulin R U-500 reduces injection volume by 80 percent. However, dosing errors with U-500 can be life-threatening; dedicated U-500 syringes and KwikPens are essential.
Side Effects
- Hypoglycemia — most common, especially if injected and meal is delayed or skipped
- Weight gain — modest, typical of intensified insulin therapy
- Injection site reactions — redness, itching, small lumps
- Lipodystrophy (lipohypertrophy or lipoatrophy) from repeated injections in the same spot
- Hypokalemia (low potassium) — particularly with IV doses
- Allergic reactions — local or rare anaphylaxis
- Peripheral edema, especially with thiazolidinediones
- U-500 specific: severe hypoglycemia from dosing errors when wrong syringe is used
Storage and Handling
- Unopened vials: refrigerate at 36 to 46 °F (2 to 8 °C)
- In use: U-100 vials room temperature for up to 31 days; U-500 vials up to 40 days
- Do not freeze; do not expose to direct sunlight
- Solution is clear and colorless — discard if cloudy, discolored, or contains particles
- Do not share vials or pens between people
- U-500 must be drawn up only with U-500-specific devices to prevent fatal overdoses
Cost and Access
- Humulin R U-100 vial: about $25 to $50 retail without insurance
- Humulin R U-500 vial: about $200 to $500 retail
- Novolin R (the Novo Nordisk equivalent) at Walmart (ReliOn): about $25 per vial over the counter
- Medicare Part D and Medicaid cover regular insulin at the federal $35 monthly cap
- Eli Lilly patient assistance programs available
Practical Tips
- Inject 30 minutes before eating — set a timer if needed
- If a meal is going to be delayed, delay the injection
- Keep glucose tablets or fast-acting carbohydrate nearby — the 2 to 4 hour peak can cause late post-meal lows if you eat less than planned
- Do not switch between U-100 and U-500 without specific prescriber guidance — dosing scales differ entirely
- If you are admitted to the hospital, expect to be put on IV regular insulin if your blood sugar requires aggressive control
Related Reading
For more, see our overview of diabetes treatment, the page on insulin sliding scale, and the comparison guide on insulin types.
The Bottom Line
Humulin R is regular human insulin — short-acting, with onset in 30 minutes, peak at 2 to 4 hours, and duration of 5 to 8 hours. It is the only insulin approved for intravenous use, making it the standard for hospital insulin drips, DKA treatment, and emergency hyperkalemia management. A U-500 concentrated formulation exists for severe insulin resistance and requires dedicated handling. For routine outpatient mealtime use, rapid-acting analogs are usually preferred because they better match meal-time glucose rises, but Humulin R remains an affordable option at about $25 to $50 per vial. Side effects include hypoglycemia, weight gain, and injection site reactions. Talk to your prescriber to individualize regular insulin use to your situation.
