Insulin

Human insulin: Humulin, Novolin, Actrapid, Insuman. Rapid analogues: lispro (Humalog, Admelog, Lyumjev), aspart (NovoLog/NovoRapid, Fiasp), glulisine (Apidra). Basal analogues: glargine (Lantus, Toujeo, Basaglar, Semglee, Rezvoglar), detemir (Levemir), degludec (Tresiba), icodec (Awiqli, weekly), efsitora alfa (Onswik, weekly). Inhaled: Afrezza

Metabolic & weight

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Note on this profile. Insulin is a life-sustaining prescription hormone used by hundreds of millions of people, not a research compound, and this is an overview page rather than a prescribing guide. It is included because insulin is the archetypal peptide hormone, because it anchors the metabolic axis that many other peptides on this site act on, and because non-medical use for muscle gain exists and has killed people. Nothing here is dosing advice: insulin doses are individualised by a prescriber and depend entirely on the person, the product and the moment.

Summary

Class: Naturally occurring 51-amino-acid peptide hormone in two chains (A chain 21, B chain 30) joined by two disulfide bonds, with a third within the A chain; made as a single precursor (proinsulin) and released with its connecting peptide (C-peptide). Analogues alter one to several residues or add fatty-acid or albumin-binding groups to speed up or slow down absorption
Mechanism: Binds the insulin receptor (a tyrosine kinase) on muscle, fat and liver cells, driving glucose uptake and storage, switching off liver glucose output and fat breakdown, and promoting protein synthesis — the body's main anabolic and glucose-lowering signal
Routes studied: Subcutaneous injection or pump infusion (standard); intravenous (hospital); inhaled (Afrezza); intranasal (research, for brain delivery); oral (decades of failed attempts; one weekly oral candidate reached phase 3)
Half-life: Regular insulin IV ~5–6 min; subcutaneous action depends on formulation — rapid analogues peak 1–2 h and last 3–5 h; glargine/detemir ~12–24 h; degludec ~25 h half-life, >42 h action; icodec ~196 h (8 days); efsitora ~17 days
Storage: Unopened: refrigerate 2–8 °C, never freeze. In use: room temperature (below 25–30 °C) for 28 days for most products (42 days detemir, 56 days degludec and glargine U300; check the label); protect from heat and light
Regulatory status: Approved medicine everywhere; WHO Essential Medicine; biosimilars and interchangeable products widely available

Doses are as reported in studies or by the community — never recommendations.

1What it is

Insulin is the hormone that lets the body store the energy from a meal. The beta cells of the pancreatic islets release it when glucose rises; it opens glucose channels in muscle and fat, tells the liver to stop making glucose and start making glycogen, and tells fat cells to hold onto fat. Without it, as in type 1 diabetes, blood glucose climbs while the body starves and burns fat to ketones — a condition that was uniformly fatal until Banting, Best, Collip and Macleod in Toronto isolated insulin from animal pancreases in 1921 and injected the first patient in January 1922. It was the first peptide hormone used as a drug, the first protein to have its amino-acid sequence determined (Sanger, 1955), and in 1982 the first recombinant-DNA medicine (Humulin, made in E. coli).

Since the 1990s the field has moved to analogues: molecules with small deliberate changes that either absorb faster (lispro, aspart, glulisine, and the "ultra-rapid" Fiasp and Lyumjev formulations) to match meals, or absorb more slowly and evenly (glargine, detemir, degludec) to provide a flat background. Two once-weekly basal insulins reached approval in 2024–2026: icodec (Awiqli; EU 2024, US March 2026 for type 2 diabetes) and efsitora alfa (Onswik; US Sept 2026 for type 2 diabetes). Today roughly 8–9 million people live with type 1 diabetes and many more with type 2 use insulin.

Non-medical use. Insulin is misused in bodybuilding for its anabolic and glycogen-loading effects, typically rapid-acting insulin around training with large carbohydrate intakes, often alongside growth hormone or anabolic steroids. This is documented in the medical literature mostly through case reports of severe hypoglycaemia, brain injury and death (Evans & Lynch 2003, Br J Sports Med; Rich 1998). There is no controlled evidence that it adds muscle in healthy people beyond what nutrition and training deliver, and the margin between an "anabolic" dose and a fatal one is small and unpredictable. It is included here so that the risks are stated plainly, not as a protocol.

2How it's thought to work

Insulin binds its receptor, which phosphorylates IRS proteins and activates the PI3K–Akt pathway (metabolic effects: GLUT4 translocation to the cell surface, glycogen synthesis, lipogenesis, suppression of gluconeogenesis) and the MAPK pathway (growth and gene-expression effects).

Through mTOR it stimulates protein synthesis and suppresses protein breakdown; at physiological levels it is permissive rather than driving — amino acids and resistance exercise are the main triggers for muscle protein synthesis, and insulin's contribution saturates at modest concentrations.

It suppresses lipolysis strongly even at low concentrations; this is why insulin excess promotes fat gain and why its "anabolic" reputation in bodybuilding is only half the story.

Hypoglycaemia occurs when insulin action exceeds glucose supply; the brain depends on glucose and fails within minutes when it falls far enough.

Insulin resistance (reduced response per unit) underlies type 2 diabetes and is worsened by excess body fat, inactivity, growth hormone, cortisol and some medicines — relevant to GH users on this site.

The hormone at its receptor, which is a tyrosine kinase rather than a G-protein receptor. Glucose transporters move to the cell surface, sugar enters, and the liver stops making more.Schematic — not to scale

3What the research shows

Graded A (historic and ongoing)

Survival and glycaemic control in type 1 diabetes

Insulin converts a fatal disease into a chronic one. The DCCT (n=1,441; 1983–1993) showed intensive insulin therapy (HbA1c ~7% vs ~9%) cut retinopathy by 76%, nephropathy by ~50% and neuropathy by 60% (DCCT Research Group 1993, NEJM), with cardiovascular benefit persisting for decades (EDIC follow-up; Nathan 2005, NEJM).

Type 2 diabetes

UKPDS showed intensive glucose control with insulin or sulfonylureas reduced microvascular complications (UKPDS 33, 1998, Lancet) with later "legacy" reductions in heart attack and death (Holman 2008, NEJM). ORIGIN (n=12,537) found basal glargine neutral for cardiovascular outcomes and cancer over 6 years, settling an earlier scare (ORIGIN Investigators 2012, NEJM). [3][4]

Graded A (modest differences)

Analogue versus human insulin

Rapid analogues lower post-meal glucose and reduce hypoglycaemia slightly versus regular human insulin; basal analogues reduce nocturnal hypoglycaemia versus NPH with similar HbA1c (Cochrane reviews). DEVOTE (n=7,637) showed degludec was non-inferior to glargine for cardiovascular events with 40% less severe hypoglycaemia (Marso 2017, NEJM). [5]

Once-weekly basal insulin

ONWARDS 1–6 trials: icodec was non-inferior or superior to daily basal insulins on HbA1c in type 2 diabetes with similar hypoglycaemia, but in type 1 diabetes (ONWARDS 6) gave more hypoglycaemia (Rosenstock 2023, NEJM; Russell-Jones 2023, Lancet). QWINT 1–5 trials for efsitora gave a similar picture: HbA1c reductions of 0.8–1.3 percentage points, non-inferior to glargine or degludec, with type 1 diabetes excluded from the approved indication because of hypoglycaemia. [6]

Closed-loop (automated insulin delivery)

Hybrid closed-loop pumps increase time-in-range by roughly 10–15 percentage points and reduce hypoglycaemia versus sensor-augmented pumps (Brown 2019, NEJM, and many since). [7]

Graded A (negative/mixed)

Intranasal insulin for cognition

A phase 2/3 trial of intranasal insulin in Alzheimer's disease found no cognitive benefit over 12 months (Craft 2020, JAMA Neurol), although device problems complicated the result. [10]

Graded B/—

Anabolic effect in healthy adults

Infusion studies show insulin reduces muscle protein breakdown and modestly increases net protein balance when amino acids are supplied, but the effect saturates at physiological concentrations (Fujita 2006; Abdulla 2016 meta-analysis, Diabetologia). No controlled trial supports supraphysiological insulin for muscle gain; the bodybuilding literature is case reports of harm. [8]

4Reported side effects and interactions

Literature-reported

hypoglycaemia is the principal and potentially fatal adverse effect (confusion, sweating, tremor, seizures, coma); severe hypoglycaemia occurs about 0.3–1 episodes per patient-year in intensively treated type 1 diabetes. Weight gain (2–4 kg typical on starting); lipohypertrophy (fatty lumps at over-used injection sites, which then absorb insulin erratically) and the rarer lipoatrophy; injection-site reactions; hypokalaemia (insulin drives potassium into cells — important with IV insulin and overdose); peripheral oedema on starting; transient worsening of retinopathy with rapid glucose improvement; allergic reactions, rarely anaphylaxis (to insulin or excipients such as metacresol or protamine). Insulin antibodies are common and usually harmless. A theoretical mitogenic concern with glargine was not borne out in ORIGIN.

Community-reported

Community-reported (non-medical use). hypoglycaemia during or after training, sometimes hours later and during sleep; cases of hypoglycaemic brain injury and death; fat gain. Users describe needing to eat large amounts of carbohydrate to stay safe, which largely explains any weight gain.

Theoretical. chronic supraphysiological insulin in a non-diabetic person promotes insulin resistance and fat storage; combination with growth hormone (which raises glucose) is sometimes rationalised as "balancing", which is pharmacologically naive and makes the hypoglycaemia timing less predictable.

Interactions. beta-blockers mask the adrenergic warning signs of hypoglycaemia and can prolong it; alcohol impairs the liver's glucose output and increases hypoglycaemia risk for hours; sulfonylureas, GLP-1 receptor (see Semaglutide), SGLT2 inhibitors and pramlintide all increase hypoglycaemia risk or reduce insulin requirement; corticosteroids, growth hormone, thiazides, atypical antipsychotics and some HIV drugs raise requirements; thiazolidinediones with insulin increase fluid retention and heart failure risk; salicylates and MAO inhibitors can enhance insulin's effect.

Markers researchers commonly monitor

Per standard diabetes care:

Marker	Why it's watched
Blood glucose by fingerstick or continuous glucose monitor (CGM)	the core measure; CGM metrics (time in range 3.9–10 mmol/L, time below range, glucose variability) have become standard trial endpoints.
HbA1c	2–3-month average glucose; every 3–6 months.
Serum potassium	with intravenous insulin, DKA treatment or any overdose.
Body weight and body composition	weight gain is expected on starting; relevant to anyone using it for other reasons.
Lipid panel, liver enzymes, eGFR and urine albumin	complications screening in people with diabetes; kidney function also changes insulin clearance.
C-peptide	measures the body's own insulin production (exogenous insulin contains none), used to distinguish diabetes types and to detect factitious or non-medical insulin use.
Injection-site inspection	for lipohypertrophy, which causes erratic absorption.
Retinal examination	annually; rapid glucose improvement can transiently worsen retinopathy.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Insulin is supplied as a ready-to-use solution or suspension (NPH and premixed insulins are cloudy suspensions and must be rolled gently to mix; clear insulins are not shaken). It is never and the calculator on this site does not apply to it. Three practical points dominate safety: use only insulin syringes or pens matched to the product's concentration (a syringe with U-500 insulin delivers five times the intended dose); rotate injection sites to avoid lipohypertrophy; and do not inject into a limb that is about to be exercised, which speeds absorption. Pens and vials in use are kept at room temperature; heat (a car in summer) and freezing both destroy activity.

6Commonly studied alongside

Glucagon and dasiglucagon (profile 127), the rescue agent for its main side effect; pramlintide (amylin analogue, approved as an insulin add-on); GLP-1 receptor agonists (Semaglutide, Tirzepatide, Liraglutide profiles) which reduce insulin requirements; metformin and SGLT2 inhibitors; C-peptide (its own co-secreted peptide, studied for neuropathy); growth hormone and IGF-1 (opposing and overlapping metabolic effects — see Ipamorelin, Tesamorelin). In the non-medical context it is discussed with growth hormone, IGF-1 LR3 and anabolic steroids, where the risk is additive and uncontrolled.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved (many products). Human insulins are available without prescription in most states (over-the-counter regular, NPH and 70/30); analogues are prescription-only. Interchangeable biosimilar glargine (Semglee, 2021; Rezvoglar). Awiqli (icodec) approved March 2026 and Onswik (efsitora) Sept 2026, both for type 2 diabetes only. Federal $35/month copay cap for Medicare and voluntary manufacturer caps since 2023
European Union	EMA-authorised products including Awiqli (2024, type 1 and type 2 diabetes); prescription-only
United Kingdom	MHRA-licensed; prescription-only; NHS-funded; hybrid closed-loop recommended by NICE for type 1 diabetes (2023)
Australia	TGA-registered; PBS-subsidised; prescription-only
South Africa	SAHPRA-registered; prescription-only; on the Essential Medicines List
Sport	Prohibited by WADA at all times (S4 — Hormone and metabolic modulators: insulins and insulin-mimetics); athletes with diabetes require a Therapeutic Use Exemption

8Open questions

Whether once-weekly insulins can be made safe enough for type 1 diabetes.
Glucose-responsive ("smart") insulins that switch on only when glucose is high — in early trials for decades.
The real contribution of insulin, as opposed to amino acids and training, to human muscle growth; and whether any safe anabolic window exists (no evidence that it does).
Access and affordability remain the largest global problem with a 100-year-old drug.

9References

1Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA (1922). Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J. PubMed
2Diabetes Control and Complications Trial Research Group (1993). The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. NEJM. PubMed
3UK Prospective Diabetes Study (UKPDS) Group (1998). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. PubMed
4ORIGIN Trial Investigators (2012). Basal insulin and cardiovascular and other outcomes in dysglycemia. NEJM. PubMed
5Marso SP et al. (2017). Efficacy and safety of degludec versus glargine in type 2 diabetes (DEVOTE). NEJM. PubMed · DOI
6Rosenstock J et al. (2023). Weekly icodec versus daily glargine U100 in type 2 diabetes without previous insulin (ONWARDS 1). NEJM. PubMed · DOI
7Brown SA et al. (2019). Six-month randomized, multicenter trial of closed-loop control in type 1 diabetes. NEJM. PubMed · DOI
8Abdulla H et al. (2016). Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis. Diabetologia. PubMed · DOI
9Evans PJ, Lynch RM (2003). Insulin as a drug of abuse in body building. Br J Sports Med. PubMed · DOI
10Craft S et al. (2020). Safety, efficacy, and feasibility of intranasal insulin for the treatment of mild cognitive impairment and Alzheimer disease dementia: a randomized clinical trial. JAMA Neurol. PubMed · DOI
11American Diabetes Association (2026). Standards of Care in Diabetes — pharmacologic approaches to glycemic treatment. Diabetes Care. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

10Community

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11Page history

30 Oct 2026Profile published — awaiting medical review

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