Insulin

Also known as human insulin, insulin lispro (Humalog), insulin aspart (NovoRapid/NovoLog), insulin glargine (Lantus/Toujeo), insulin degludec (Tresiba), NPH insulin

The archetypal therapeutic peptide: the glucose-lowering pancreatic hormone and its engineered analogues.

clinically proven Hormonal & sexual approved drug

At a glance

Category: Hormonal & sexual
Status: approved drug
Made from: recombinant Modern insulin is recombinant human insulin or an engineered analogue, expressed in Escherichia coli or in yeast.
Route: subcutaneous injection or continuous subcutaneous infusion by pump; intravenous in hospital; inhaled (Afrezza) as a niche option
Half-life: Regular human insulin has a plasma half-life of about 4-6 minutes intravenously. What matters clinically is the absorption profile from the subcutaneous depot, which ranges from roughly 3-5 hours of action for rapid analogues to more than 42 hours for insulin degludec.
Onset: rapid-acting analogues act within 10-20 minutes; regular human insulin within 30-60 minutes; long-acting analogues reach steady state over 2-4 days
Molecular weight: 5808 g/mol (human insulin); analogues 5800-6100 g/mol
Sequence: A chain: GIVEQCCTSICSLYQLENYCN (21 residues). B chain: FVNQHLCGSHLVEALYLVCGERGFFYTPKT (30 residues). The two chains are joined by disulfide bridges A7-B7 and A20-B19, with an intrachain bridge A6-A11. Analogues differ by small substitutions: lispro swaps B28 proline and B29 lysine; aspart replaces B28 proline with aspartate; glargine adds two arginines to the B chain and substitutes A21 asparagine with glycine; detemir and degludec are acylated with fatty acid chains at B29.

In clinical use since 1922 and on every essential medicines list in the world. Modern products are recombinant human insulin or engineered analogues, approved by the EMA, FDA and every other major regulator. Prescription only in the EU; in the US some older human insulins are available without a prescription in certain states, which is one route by which non-medical users obtain it.

Doping status: Prohibited at all times (WADA S4, hormone and metabolic modulators)

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Insulin extracted from bovine and porcine pancreas is a historical product, withdrawn from most markets; current products contain no animal material.

Mechanism of action

Insulin binds the insulin receptor, a disulfide-linked transmembrane receptor tyrosine kinase. Binding triggers autophosphorylation and recruitment of insulin receptor substrate proteins (IRS-1/2), which activate phosphoinositide 3-kinase and Akt. The best-known consequence is translocation of GLUT4 glucose transporters to the plasma membrane in skeletal muscle and adipose tissue, allowing glucose uptake. In parallel, Akt activates glycogen synthase, suppresses hepatic gluconeogenesis and glycogenolysis, and inhibits adipose lipolysis. A second branch of the receptor signal runs through Ras and MAPK and mediates the mitogenic and growth-promoting effects.

Insulin is not only a glucose hormone; it is the body's principal anabolic and anti-catabolic signal. It stimulates amino acid uptake into muscle, activates mTOR-dependent protein synthesis and suppresses protein breakdown. This is the pharmacological basis for its misuse in bodybuilding, and also the reason that misuse is so dangerous: the anabolic effect cannot be separated from the glucose-lowering effect.

The analogue classes are engineering solutions to a formulation problem. Native insulin self-associates into zinc-coordinated hexamers, which must dissociate into monomers before absorption; this is what makes regular human insulin slow. Rapid-acting analogues (lispro, aspart, glulisine) carry substitutions at the hexamer interface that weaken self-association, so they dissociate and absorb faster — onset in 10-20 minutes, duration 3-5 hours, which better matches a meal. Faster formulations (faster aspart, ultra-rapid lispro) add excipients such as niacinamide to speed absorption further.

Long-acting analogues work by delaying release from the depot. Insulin glargine has an isoelectric point shifted toward neutral, so it precipitates as microcrystals on injection into subcutaneous tissue at pH 7.4 and redissolves slowly, giving roughly 20-24 hours of relatively flat action (longer for the concentrated U-300 form). Insulin detemir and insulin degludec are acylated with fatty diacid chains that bind albumin; degludec additionally forms soluble multihexamer chains in the depot that disassemble gradually, giving a half-life of about 25 hours and a duration beyond 42 hours with very low day-to-day variability. NPH insulin, the older intermediate option, achieves delay by crystallising insulin with protamine — which is why NPH is a suspension and must be resuspended before every injection.

This pharmacology explains the central safety fact. Once a long-acting insulin has been injected subcutaneously there is no way to retrieve it or reverse it. The depot will release insulin for the next 24 to 42 hours regardless of what the blood glucose does.

What the research shows

Insulin is arguably the most thoroughly evidenced drug in medicine. Its efficacy in type 1 diabetes is not a matter of trial evidence but of survival: without it, type 1 diabetes is fatal. Large randomised trials have established what degree of glycaemic control is worth pursuing and at what cost in hypoglycaemia. There is, by contrast, no clinical evidence base whatsoever for using insulin as a performance or physique-enhancing drug in people without diabetes.

Research in humans

The Diabetes Control and Complications Trial (New England Journal of Medicine, 1993) randomised 1441 people with type 1 diabetes to intensive versus conventional insulin therapy and found that intensive control reduced the development of retinopathy by 76%, progression of albuminuria by 54% and clinical neuropathy by 60% — at the cost of a two- to threefold increase in severe hypoglycaemia 1. Its EDIC follow-up showed persistent benefit decades later: after roughly 17 years, intensive therapy had reduced cardiovascular disease risk by 42% 5. UKPDS 33 established analogous, smaller benefits in type 2 diabetes, with a 25% reduction in microvascular endpoints but no significant macrovascular benefit 6. Head-to-head trials of long-acting analogues versus NPH consistently show similar HbA1c with less nocturnal hypoglycaemia; DEVOTE compared degludec with glargine in high-cardiovascular-risk type 2 diabetes and found degludec non-inferior for major cardiovascular events (8.5% versus 9.3%) with significantly less severe hypoglycaemia (4.9% versus 6.6%) 7.

Animal and lab research

Animal work is of historical rather than current relevance: the isolation of insulin from canine and bovine pancreas by Banting, Best, Collip and Macleod in 1921-22 and the demonstration that it reversed experimental diabetes in dogs. Every question of clinical importance has since been answered in humans.

Caveats. The main evidential gap is not in the therapeutic literature but in the non-medical one. Claims that insulin improves muscle mass or nutrient partitioning in healthy trained people rest on inference from its anabolic signalling, not on controlled trials — no such trials exist, and none could ethically be designed at the doses used. The forensic and emergency medicine literature on insulin misuse consists of case reports and case series, which describe outcomes without quantifying risk 2 3. Insulin's real-world hypoglycaemia burden is systematically underestimated in trials, because trial populations are selected and supervised in ways ordinary users are not.

What it is used for

Type 1 diabetes mellitus, where insulin replacement is obligatory and lifelong
Type 2 diabetes mellitus when oral agents and GLP-1 receptor agonists no longer achieve adequate control, or where there is significant beta-cell failure
Gestational diabetes not controlled by diet, and pre-existing diabetes during pregnancy
Diabetic ketoacidosis and hyperosmolar hyperglycaemic state, by intravenous infusion
Hyperkalaemia, given intravenously with glucose to shift potassium into cells
Stress hyperglycaemia in critical illness and in patients on high-dose glucocorticoids or parenteral nutrition
Misuse in bodybuilding and strength sport, where it is taken around training or meals for its anabolic and nutrient-partitioning effects. This is not a therapeutic use, is prohibited in sport, and is a well-documented cause of hospitalisation, permanent neurological injury and death

Dosing

Dose

There is no single dose. Four different regimens are described separately in the notes below, and they are not variants of one another: they differ in indication, in route, and in whether the figure is per kilogram, per kilogram per hour, or absolute.

Frequency

Basal insulin once (sometimes twice) daily; rapid-acting insulin with each meal containing carbohydrate; or continuous subcutaneous infusion via pump with meal boluses

Route

Subcutaneous into abdomen, thigh, buttock or upper arm, rotating sites; intravenous only in hospital

Duration

Lifelong in type 1 diabetes; indefinite in type 2 diabetes once started, though it can sometimes be withdrawn after substantial weight loss or the addition of other agents

Type 1 diabetes, subcutaneous, ongoing: the total daily requirement is typically 0.4-1.0 units per kilogram of body weight per day, conventionally split roughly half as basal and half as mealtime bolus. This is a per-kilogram figure — for a 70 kg adult it is roughly 28-70 units a day in total, not per injection.
Type 2 diabetes, basal insulin, subcutaneous, starting dose: the insulin glargine label gives 0.2 units per kilogram, or up to 10 units, once daily in insulin-naive patients, titrated against fasting glucose 8. This is the one figure on this page that is a fixed starting point rather than a calculation.
Diabetic ketoacidosis, intravenous infusion, hospital only: approximately 0.1 units per kilogram per hour. Note the per-hour denominator — for a 70 kg adult this is about 7 units an hour, and reading it as a daily or a single dose is a large error in either direction.
Hyperkalaemia, single intravenous dose, hospital only: 10 units of regular insulin given with 25 g of glucose. This is an absolute dose, not per kilogram, and it is given for a potassium problem rather than a glucose one.
Insulin dosing is individualised in a way few drugs are. It depends on carbohydrate intake, activity, illness, weight, renal function, time of day and the individual's insulin sensitivity, and it is adjusted continuously against measured glucose. Any figure quoted as a general dose is a starting point for titration, not a prescription.
Insulin-to-carbohydrate ratios and correction factors are calculated per person; commonly used rules of thumb (such as the '500 rule' and '1800 rule') are teaching heuristics, not validated formulas.
The figures above are standard clinical starting points from prescribing information and diabetes guidelines. This is reference material, not treatment advice.
There is no established or safe dose for non-diabetic use. Doses circulated in bodybuilding forums have no validated basis, take no account of individual insulin sensitivity, and have repeatedly resulted in severe hypoglycaemia. The margin between a dose that produces the sought-after effect and one that causes coma is small and unpredictable, and it narrows further with fasting, alcohol, endurance exercise, heat, and injection into a limb that is subsequently trained.
Concentration errors are a recurring cause of serious harm: insulin is supplied at U-100, U-200, U-300 and U-500, and units on a U-100 syringe do not correspond to units of a U-300 pen.
The bodybuilding pattern that circulates for this drug is set out in the Protocols section below and labelled as such. The label directs insulin at diabetes, titrated against measured glucose; the circulating use is non-therapeutic self-dosing in people with normal pancreatic function, it has no validated basis, and it is a documented cause of death 3 2. It is recorded because readers encounter it, not because any non-diabetic dose is safe.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

Lantus (insulin glargine) initiation in type 2 diabetes

approved product information

Source: Lantus (insulin glargine) EPAR product information, EMA

Starting dose	10 units once daily, or 0.2 units/kg once daily, at any time of day but at the same time each day
Thereafter	adjusted individually against fasting plasma glucose

This is the one insulin regimen that is genuinely a fixed starting point. Everything else in insulin dosing is individual titration, and the type 1, ketoacidosis and hyperkalaemia regimens quoted elsewhere come from clinical guidelines rather than from any product information. Insulin has no dose ceiling and no antidote, and the gap between a therapeutic and a dangerous dose is narrower than for anything else on this site.

Bodybuilding post-workout use (circulating, off-label, dangerous)

user protocol — not validated

Source: Bodybuilding forums and coach 'protocols'; documented in emergency-medicine and forensic case reports

This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.

What circulates	rapid-acting insulin (lispro or aspart) around training, commonly cited at a few units and titrated up against carbohydrate intake — the figures vary widely between sources and have no validated basis
How reports diverge	some describe fixed small amounts after a workout; others borrow 'units per gram of carbohydrate' rules from diabetes teaching; long-acting insulin is used by some and specifically warned against by others
Documented outcome	severe hypoglycaemia, coma and death, including in people who had injected insulin uneventfully many times before

This sits beside the clinical block on purpose. The label directs insulin at diabetes, titrated against measured glucose; what circulates in bodybuilding is a non-therapeutic practice in people with normal pancreatic function, where endogenous insulin secretion continues on top of the injected dose and can overwhelm the counter-regulatory response. There is no established or safe non-diabetic dose, and the reported figures diverge widely — different sources cite different unit counts, different insulins and different carbohydrate rules copied from diabetes care — which is itself the point: there is no agreed schedule because none has ever been studied. Hypoglycaemia from self-administered insulin is a documented cause of death, described in the emergency-medicine and forensic literature 3 2, and post-mortem diagnosis is difficult because the autopsy findings are non-specific 2. Long-acting analogues are the most dangerous in this setting, because once injected the depot cannot be removed or neutralised and keeps releasing insulin for a day or more. This is recorded because it circulates, not because any part of it is safe.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Vial sizes: 10 ml vial (U-100), 3 ml cartridge and prefilled pen (U-100, U-200, U-300), 20 ml vial (U-500, US)
Storage: Unopened vials, cartridges and pens refrigerated at 2-8 °C until the expiry date. Never freeze; frozen insulin must be discarded. Once in use, most products are kept at room temperature below 25-30 °C and discarded after 28 days, with important exceptions — insulin degludec pens are good for 8 weeks in use, and some products specify other periods. Protect from direct light and heat.

Worked example

Not applicable. All marketed insulins are ready-to-use liquids: clear solutions for rapid-acting analogues, regular human insulin, glargine, detemir and degludec, and white suspensions for NPH and premixed insulins. Nothing is reconstituted from powder. Insulin is only diluted in hospital, for intravenous infusion in 0.9% sodium chloride, or with a manufacturer-supplied sterile diluent for very small paediatric doses.

NPH and premixed insulins are suspensions and must be resuspended by rolling the pen or vial gently between the palms and inverting it around ten times before each dose. Shaking causes foaming and inaccurate dosing. Clear insulins should never be used if they look cloudy or contain particles; cloudy insulins should never be used if they remain clumped after mixing. Insulin sold outside pharmacy channels, or repackaged, is a particular concern because potency and sterility are not assured and the concentration may not be what the label says.

Safety

Side effects

Hypoglycaemia — the dominant and potentially fatal adverse effect, and the one the label names as most common and possibly life-threatening 8. Early symptoms are sweating, tremor, palpitations, hunger, anxiety and pallor; as glucose falls further, confusion, aggression, slurred speech and incoordination appear, followed by seizures, coma, permanent brain injury and death. Severe hypoglycaemia is a medical emergency requiring oral carbohydrate if conscious, or intramuscular glucagon or intravenous glucose if not
Hypoglycaemia unawareness: repeated episodes blunt the adrenergic warning symptoms, so later episodes can progress to unconsciousness without any warning at all; the label notes the risk rises with longstanding diabetes and with sympatholytic drugs 8
Nocturnal hypoglycaemia, which may not wake the person
Weight gain, expected and dose-related 8
Lipodystrophy at overused injection sites, which then absorbs insulin erratically and destabilises control 8; lipoatrophy, now rare
Injection site reactions, pruritus and rash; rarely severe generalised allergy including anaphylaxis 8
Hypokalaemia, since insulin drives potassium intracellularly; the label warns it may be life-threatening 8 and it is clinically important with large doses and in critical care
Peripheral oedema and, rarely, fluid retention and worsening heart failure, particularly when insulin is combined with a thiazolidinedione 8
Transient worsening of diabetic retinopathy when very poor control is corrected rapidly
Acute painful neuropathy (treatment-induced neuropathy) after rapid improvement in glycaemia
Insulin antibodies, usually clinically irrelevant with modern recombinant products
In non-medical use specifically: fatal and near-fatal hypoglycaemia is repeatedly documented in bodybuilders, including in people who had used insulin uneventfully many times before. Long-acting analogues are the most dangerous in this context, because once injected, the depot cannot be removed, cannot be neutralised, and continues releasing insulin for a day or more. Falling asleep after a dose, drinking alcohol, or simply eating less than planned has been enough to kill people

Do not use if

Hypoglycaemia — insulin is contraindicated during an episode of hypoglycaemia 8
Hypersensitivity to the specific insulin product or its excipients 8 (metacresol, phenol, protamine, zinc)
Non-medical use for muscle gain or performance. There is no dose of insulin that is safe for a person with normal pancreatic function to self-administer for these purposes. Endogenous insulin secretion continues on top of the injected dose, the counter-regulatory response can be overwhelmed, and the resulting hypoglycaemia is frequently unwitnessed. This is not a theoretical risk: fatal cases in bodybuilders are documented in the emergency medicine and forensic literature, and post-mortem diagnosis is difficult because autopsy findings are non-specific
Use without reliable access to glucose monitoring, to fast-acting carbohydrate, and to someone who knows what has been taken and can call for help
Caution and dose reduction in significant renal or hepatic impairment, since insulin clearance falls and hypoglycaemia risk rises substantially
Caution in hypokalaemia, which insulin will worsen
Extreme caution when combined with alcohol, prolonged fasting, endurance exercise or a sauna, all of which potentiate and prolong the glucose-lowering effect

Interactions

Agents that increase the glucose-lowering effect and therefore hypoglycaemia risk include sulfonylureas, meglitinides, GLP-1 receptor agonists, SGLT2 inhibitors, alcohol, salicylates, ACE inhibitors, MAO inhibitors, fibrates, fluoxetine, pentoxifylline, somatostatin analogues and sulfonamide antibiotics. Agents that reduce the effect and raise insulin requirements include glucocorticoids, thiazide and loop diuretics, sympathomimetics, thyroid hormone, atypical antipsychotics (particularly olanzapine and clozapine), oral contraceptives, danazol, protease inhibitors and growth hormone — the last of these is directly relevant, since growth hormone and GH secretagogues are frequently used alongside insulin in bodybuilding and blunt insulin sensitivity in a way that invites dose escalation. Beta-blockers, clonidine, guanethidine and reserpine mask the adrenergic warning symptoms of hypoglycaemia 8 while non-selective beta-blockers also impair the counter-regulatory glucose response, a combination that turns a manageable episode into a dangerous one. Thiazolidinediones combined with insulin increase the risk of fluid retention and heart failure 8.

Sources

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus (DCCT)New England Journal of Medicine, 1993
Insulin and Oral Hypoglycemic Drug Overdose in Post-Mortem Investigations: A Literature ReviewBiomedicines, 2022
Severe Hypoglycemia Due to Cryptic Insulin Use in a BodybuilderJournal of Emergency Medicine, 2019
Lantus (insulin glargine) - EPAR product informationEuropean Medicines Agency
Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes (DCCT/EDIC)New England Journal of Medicine, 2005
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)The Lancet, 1998
Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes (DEVOTE)New England Journal of Medicine, 2017
LANTUS (insulin glargine) injection, for subcutaneous use - full prescribing informationDailyMed, Sanofi-Aventis