Regular human insulin
The original recombinant human insulin, still the standard intravenous insulin in hospitals
Regular insulin is unmodified human insulin, made by recombinant DNA technology and approved in 1982 as Humulin R, the first recombinant protein drug. Injected 30 minutes before a meal, it is a short-acting mealtime insulin; given intravenously, it is the insulin hospitals use for diabetic ketoacidosis and critical illness.
What is it?
Regular insulin has the same sequence as the insulin the pancreas makes. Under the skin it forms clusters that must break apart before absorption, so it starts working in about half an hour and is taken before meals; the label advises injecting about 30 minutes before eating. According to the Humulin R label, its apparent half-life after a subcutaneous dose is about 1.5 hours, ranging from 40 minutes to 7 hours, and after an intravenous dose about 20 minutes to 1 hour depending on the dose.
Faster analogues such as lispro and aspart have replaced it for most mealtime use. In adolescents with type 1 diabetes, a glargine and lispro regimen gave lower blood glucose and 43% less nocturnal hypoglycaemia than NPH with regular insulin. Over two meals in type 2 diabetes, aspart produced a smaller glucose rise. Yet cost keeps regular insulin in use: in a 136-patient trial with a wearable patch pump, switching to it was non-inferior for HbA1c at lower pharmacy cost.
In hospital it is the intravenous reference. In diabetic ketoacidosis, subcutaneous lispro or aspart can match intravenous regular insulin in mild and moderate cases, but only when tested against it. Added to parenteral nutrition bags it controlled glucose as well as glargine with fewer lows, and in intensive care its effect lingers longer after an infusion stops than lispro's. The label allows intravenous use only under medical supervision, at 0.1 to 1 unit/mL in saline.
The concentrated U-500 form carries five times as much insulin per millilitre for people with severe insulin resistance. In a 24-week trial it lowered HbA1c by more than 1% whether given two or three times a day. Intravenous regular insulin is also used to prepare patients for cardiac PET scans.
Under the skin, the label recommends using it with an intermediate- or long-acting insulin and mixing it only with Humulin N. Its warnings centre on hypoglycaemia, which may be life-threatening, on extra glucose monitoring whenever the insulin, strength or injection method changes, and on never sharing pens or syringes. A ready-to-use bag for intravenous infusion was shown bioequivalent to regular insulin mixed on site.
Mechanism of Action
Regular insulin is unmodified human insulin; its clusters dissociate under the skin, giving a short-acting mealtime insulin.
Hexamers dissociate
Forms six-molecule clusters that must break apart before absorption, which delays onset compared with analogues.
Insulin receptor
Lowers glucose by increasing uptake in muscle and fat and suppressing liver glucose output.
Intravenous use
Can be infused intravenously under supervision, where its half-life is about 20 minutes to 1 hour (label 12.3).
Published Research
These are clinical trials of regular insulin, read from their PubMed abstracts.
U-500 regular insulin: two vs three daily doses
Both regimens lowered HbA1c (by 1.12% and 1.22%) over 24 weeks with clinical equivalence; three daily doses caused less symptomatic hypoglycaemia.
Diabetic ketoacidosis: subcutaneous lispro vs intravenous regular insulin
Hyperglycaemia corrected in about 7 hours and ketoacidosis resolved in 10 to 11 hours with either treatment.
Children with ketoacidosis: aspart vs intravenous regular insulin
In 50 children with mild or moderate ketoacidosis, subcutaneous aspart needed less total insulin than intravenous regular insulin, with no deaths or serious events.
Adolescents: glargine plus lispro vs NPH plus regular insulin
The analogue regimen gave lower fasting and daytime glucose and 43% less nocturnal hypoglycaemia on overnight profiles, with no difference around the evening meal.
Cardiac PET preparation with intravenous regular insulin
Insulin loading gave interpretable images in 30 of 30 patients against 25 of 30 with glucose loading, and was 71 minutes faster.
Cheaper insulin in a wearable patch
In 136 people with type 2 diabetes using a wearable patch pump, switching from rapid-acting analogues to U-100 regular human insulin was non-inferior for HbA1c (-0.60% against -0.38%) with no difference in hypoglycaemia or weight, at lower pharmacy cost.
Against aspart over two meals
Over two consecutive meals in type 2 diabetes, insulin aspart produced a smaller glucose rise than regular human insulin and suppressed free fatty acids and proinsulin more.
In parenteral nutrition
In 161 non-critically ill inpatients with diabetes on parenteral nutrition, regular insulin added to the bag gave similar glucose to subcutaneous glargine, with fewer hypoglycaemia episodes, though glucose was higher in the two days after nutrition stopped.
Intravenous infusion in intensive care
In a crossover trial in critically ill patients, regular insulin infusions had a longer and deeper carry-over effect on blood glucose after stopping than lispro infusions at the same dose.
A ready-to-use infusion bag
In a clamp study in 54 healthy volunteers, a premixed 1 unit/mL regular human insulin infusion in saline was bioequivalent to regular insulin prepared on site, for insulin exposure and glucose-lowering effect, with comparable safety.
Dosing Data
Regular insulin is injected under the skin about 30 minutes before meals, usually with a longer-acting insulin, or infused intravenously in hospital.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the Humulin R label and the trials above.
Contraindications & Cautions
From the label; a clinician decides.
Legal Status
Regular human insulin is an FDA-approved medicine.
Frequently Asked Questions
?What is regular insulin?
Unmodified human insulin made by recombinant DNA technology, sold as Humulin R and Novolin R: a short-acting insulin taken before meals, or given intravenously in hospital.
?How is it different from lispro or aspart?
The analogues are absorbed faster, so they can be taken closer to meals and cause less late hypoglycaemia. Regular insulin remains the standard for intravenous use.
?What is U-500 insulin?
Regular insulin at 500 units per millilitre, for people who need very large doses because of severe insulin resistance.
?Why inject it 30 minutes before eating?
Regular insulin needs time to break apart from clusters under the skin, so the label advises injecting about 30 minutes before a meal; analogues like lispro can be taken right at mealtime.
?Is it still worth using?
For cost and in hospital, yes: in one trial switching to it from analogues in a patch pump was non-inferior for HbA1c at lower cost, and intravenous regular insulin is the hospital standard.
References
- [fda-pi] Eli Lilly. HUMULIN R (insulin human injection), US prescribing information: indication, subcutaneous and intravenous administration, pharmacokinetics (apparent half-life about 1.5 hours subcutaneously; about 20 minutes to 1 hour intravenously). DailyMed version effective June 16, 2026; read September 30, 2026.
- [pubmed] Hood RC, et al. "TWO TREATMENT APPROACHES FOR HUMAN REGULAR U-500 INSULIN IN PATIENTS WITH TYPE 2 DIABETES NOT ACHIEVING ADEQUATE GLYCEMIC CONTROL ON HIGH-DOSE U-100 INSULIN THERAPY WITH OR WITHOUT ORAL AGENTS: A RANDOMIZED, TITRATION-TO-TARGET CLINICAL TRIAL." Endocr Pract, 2015;21(7):782-93. PMID: 25813411.
- [pubmed] Umpierrez GE, et al. "Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis." Am J Med, 2004;117(5):291-6. PMID: 15336577.
- [pubmed] Razavi Z, et al. "Comparison of subcutaneous insulin aspart and intravenous regular insulin for the treatment of mild and moderate diabetic ketoacidosis in pediatric patients." Endocrine, 2018;61(2):267-274. PMID: 29797212.
- [pubmed] Murphy NP, et al. "Randomized cross-over trial of insulin glargine plus lispro or NPH insulin plus regular human insulin in adolescents with type 1 diabetes on intensive insulin regimens." Diabetes Care, 2003;26(3):799-804. PMID: 12610040.
- [pubmed] Chen YC, et al. "Intravenous regular insulin is an efficient and safe procedure for obtaining high-quality cardiac (18)F-FDG PET images: an open-label, single-center, randomized controlled prospective trial." J Nucl Cardiol, 2022;29(1):239-247. PMID: 32533427.
- [fda] FDA. Drugs@FDA (openFDA): HUMULIN R, BLA 018780, approved October 28, 1982. Read September 30, 2026.
- [clinical-trial] Mora PF, et al. "Efficacy, safety and cost-effectiveness comparison between U-100 human regular insulin and rapid acting insulin when delivered by V-Go wearable insulin delivery device in type 2 diabetes." BMJ Open Diabetes Res Care, 2020;8(2). PMID: 33214190.
- [clinical-trial] Sourij H, et al. "Non-glycemic effects of insulin therapy: a comparison between insulin aspart and regular human insulin during two consecutive meals in patients with type 2 diabetes." Eur J Endocrinol, 2011;165(2):269-74. PMID: 21606190.
- [clinical-trial] Olveira G, et al. "Regular insulin added to total parenteral nutrition vs subcutaneous glargine in non-critically ill diabetic inpatients, a multicenter randomized clinical trial: INSUPAR trial." Clin Nutr, 2020;39(2):388-394. PMID: 30930133.
- [clinical-trial] Bilotta F, et al. "Insulin infusion therapy in critical care patients: regular insulin vs short-acting insulin. A prospective, crossover, randomized, multicenter blind study." J Crit Care, 2015;30(2):437.e1-6. PMID: 25466315.
- [fda-pi] Humulin R (insulin human injection) US prescribing information (Eli Lilly; DailyMed set 81199e55, effective October 31, 2023), sections 2.2-2.5; read October 6, 2026.
- [pubmed] Hompesch M, et al. "Pharmacokinetic and pharmacodynamic bioequivalence between regular human insulin (rDNA origin) in 0.9% sodium chloride ready-to-use infusion 1 U/mL and 100 U/mL concentrate diluted to 1 U/mL in healthy males." Diabetes Obes Metab, 2021;23(12):2679-2686. PMID: 34378307.
Sources & Citations
Studies were read from their PubMed abstracts; the Humulin R label from DailyMed through openFDA, read October 6, 2026, alongside the version read September 30.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.