Insulin
Insulin (human regular insulin and the analogues)
Written by Aaron CuhaReviewed Sep 2026
Also known as: Human insulin, Regular insulin, Humulin R, Novolin R, Insulin lispro, Insulin glargine, Insulin degludec, Lantus, Humalog, Tresiba
The hormone that keeps people with type 1 diabetes alive, and the most thoroughly trialled peptide in medicine. Its randomised record is equally clear about the costs: severe hypoglycaemia at 1.00 versus 0.31 events per 100 person-years in a 12,537 person trial, and weight gain of 1.6 kg where the control group lost 0.5 kg.
Overview
Insulin is a two-chain peptide hormone, an A chain of 21 amino acids and a B chain of 30 held together by disulfide bonds, secreted by pancreatic beta cells. Every compound on this site that improves glucose control is measured against what insulin does. It is included here for a plain reason: a metabolic database without insulin is not a metabolic database.
The human evidence is the largest of any peptide. In type 1 diabetes, the DCCT randomised 1,441 people to intensive or conventional therapy and, over 17 years of follow-up in the EDIC extension, intensive treatment reduced any cardiovascular event by 42 percent (95 percent confidence interval 9 to 63) and the composite of non-fatal heart attack, stroke or cardiovascular death by 57 percent. In type 2 diabetes, UKPDS 33 randomised 3,867 newly diagnosed people and achieved a median HbA1c of 7.0 percent on intensive sulfonylurea or insulin therapy against 7.9 percent on conventional treatment; 10 years after the trial ended, and despite the glucose difference disappearing within a year, the sulfonylurea-insulin group still showed a 15 percent reduction in myocardial infarction (p = 0.01) and a 13 percent reduction in death from any cause (p = 0.007).
Two later trials tested insulin itself rather than glucose control. ORIGIN randomised 12,537 people with dysglycaemia and cardiovascular risk factors to insulin glargine or standard care for a median 6.2 years: cardiovascular outcomes were neutral (hazard ratio 1.02, 95 percent confidence interval 0.94 to 1.11), severe hypoglycaemia ran at 1.00 versus 0.31 per 100 person-years, and median weight rose 1.6 kg on insulin while falling 0.5 kg on standard care. Funded by Sanofi. DEVOTE randomised 7,637 people with type 2 diabetes to insulin degludec or glargine: major cardiovascular events were non-inferior (hazard ratio 0.91) and severe hypoglycaemia was lower on degludec, 4.9 versus 6.6 percent. Funded by Novo Nordisk.
Insulin is misused outside medicine, mostly by people trying to build muscle, and that use has produced a case literature of comas and emergency admissions. It is stated on this page as a harm, with the sources named.
Mechanism of action
In humans, insulin binds the insulin receptor, a receptor tyrosine kinase, driving glucose uptake into muscle and fat, suppressing hepatic glucose output, promoting glycogen and triglyceride storage and inhibiting lipolysis. At high concentrations it also cross-activates the IGF-1 receptor, which is the pharmacological basis for the anabolic claims made by people who misuse it and also the reason those doses are dangerous. The hypoglycaemia risk follows directly from the mechanism: the dose cannot be withdrawn once injected, and the counter-regulatory response is blunted in people with long-standing diabetes.
Human evidence
The deepest randomised record of any peptide in this catalogue: tens of thousands of participants across decades, with long-term follow-up. It establishes both the benefit in diabetes and the two costs, hypoglycaemia and weight gain, in numbers.
- DCCT/EDIC, type 1 diabetes: 1,441 randomised, 17 year follow-up. Intensive insulin therapy cut any cardiovascular event by 42 percent and the hard cardiovascular composite by 57 percent.
- UKPDS 33, type 2 diabetes: 3,867 newly diagnosed people randomised. Median HbA1c 7.0 versus 7.9 percent over 10 years, fewer microvascular complications, more hypoglycaemia on intensive therapy.
- UKPDS 10 year follow-up: benefits persisted after the glucose difference vanished, with 15 percent fewer myocardial infarctions and 13 percent fewer deaths in the sulfonylurea-insulin group, the finding usually called the legacy effect.
- ORIGIN: 12,537 randomised to insulin glargine or standard care. Cardiovascular events neutral, severe hypoglycaemia more than three times as frequent (1.00 versus 0.31 per 100 person-years), median weight 1.6 kg up versus 0.5 kg down, no cancer signal. Sanofi funded.
- DEVOTE: 7,637 randomised, degludec versus glargine. Cardiovascular non-inferiority met; severe hypoglycaemia 4.9 versus 6.6 percent, a genuine head to head difference between two insulins. Novo Nordisk sponsored.
- Misuse: published case reports document coma and refractory hypoglycaemia in bodybuilders using insulin as an anabolic, from 1994 onwards. A 718 person fitness centre survey found 8.2 percent overall use of performance-enhancing drugs by randomised response, against 0.4 percent by direct questioning.
What this does not tell you: None of these trials tested insulin in people without diabetes or dysglycaemia, and none tested it for muscle gain, body composition or longevity. The diabetes trials answer what happens when insulin is used to control glucose in people who need it, and their cardiovascular findings are about glucose control as much as about insulin itself. The misuse literature is case reports and surveys: it can show that serious harm happens and roughly how common use is, and it cannot quantify risk per injection or say anything about what dose is survivable.
Reading the research record
Insulin is the reference point against which every other metabolic compound on this site is measured, and it is also the clearest example of a drug whose benefits and harms are both large and both measured. The randomised record does not need hedging: it keeps people with type 1 diabetes alive, it reduces long-term complications, and it causes hypoglycaemia and weight gain at rates that trials have quantified precisely.
The misuse has to be stated in the same voice. Insulin is used in bodybuilding to drive nutrients into muscle, often alongside growth hormone and anabolic steroids, and the published record of that practice is a case literature of comas and emergency admissions going back to 1994, not a trial literature. There is no randomised trial of insulin for muscle gain in healthy people, and there will not be one, because a dose that cannot be recalled after injection combined with an intentionally low blood glucose is not an exposure an ethics committee will approve. The Endocrine Society made that point formally: the harm evidence for performance-enhancing drugs is necessarily observational, and the users are mostly recreational weightlifters rather than competitive athletes. Insulin is prohibited in sport, and several human insulin presentations are sold over the counter in the United States, which is the awkward combination that makes this page necessary.
One more distinction worth keeping straight. Insulin resistance, the state most longevity writing is concerned with, is not treated by giving more insulin. ORIGIN tested exactly that question in 12,537 people with dysglycaemia and found cardiovascular outcomes unchanged, with more hypoglycaemia and more weight.
The evidence, charted
Fig. 1 · evidence composition
8of 10 citations (80%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 9 distinct years, 1994 to 2023, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Approved
UK
Approved
AU
Approved
CA
Approved
Approved in all four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2005
Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes
DCCT/EDIC: 1,441 people with type 1 diabetes randomised to intensive or conventional insulin therapy for a mean 6.5 years, then followed observationally. Over a mean 17 years, intensive treatment reduced any cardiovascular event by 42 percent (95 percent confidence interval 9 to 63, p = 0.02) and non-fatal myocardial infarction, stroke or cardiovascular death by 57 percent (12 to 79, p = 0.02).
New England Journal of Medicine - Human1998
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
3,867 people with newly diagnosed type 2 diabetes randomised to intensive sulfonylurea or insulin therapy or to conventional diet-first treatment. Over 10 years, median HbA1c was 7.0 percent versus 7.9 percent, an 11 percent relative reduction, with reduced microvascular complications and more hypoglycaemia in the intensive group.
Lancet - Human2008
10-year follow-up of intensive glucose control in type 2 diabetes
UKPDS post-trial monitoring of 4,209 randomised participants. Glycaemic differences disappeared within a year of the trial ending, yet at 10 years the sulfonylurea-insulin group retained reductions in any diabetes-related endpoint (9 percent, p = 0.04), microvascular disease (24 percent, p = 0.001), myocardial infarction (15 percent, p = 0.01) and death from any cause (13 percent, p = 0.007). The metformin group showed larger reductions in myocardial infarction (33 percent) and death (27 percent).
New England Journal of Medicine - Human2012
Basal insulin and cardiovascular and other outcomes in dysglycemia
ORIGIN: 12,537 people with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance or type 2 diabetes randomised to insulin glargine or standard care, median 6.2 years. Cardiovascular outcomes were neutral (hazard ratio 1.02, 95 percent confidence interval 0.94 to 1.11). Severe hypoglycaemia was 1.00 versus 0.31 per 100 person-years, and median weight rose 1.6 kg on insulin while falling 0.5 kg on standard care. No excess cancer (hazard ratio 1.00). Funded by Sanofi.
New England Journal of Medicine - Human2017
Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes
DEVOTE: 7,637 people with type 2 diabetes, 85.2 percent with established cardiovascular or kidney disease, randomised double-blind to insulin degludec or glargine U100. Major cardiovascular events occurred in 8.5 versus 9.3 percent (hazard ratio 0.91, 95 percent confidence interval 0.78 to 1.06, non-inferior). Severe hypoglycaemia occurred in 4.9 versus 6.6 percent, an absolute difference of 1.7 percentage points (rate ratio 0.60, p < 0.001 for superiority). Sponsor Novo Nordisk.
New England Journal of Medicine - Human2019
Severe Hypoglycemia Due to Cryptic Insulin Use in a Bodybuilder
Case report: a 30 year old male bodybuilder presented in coma from severe hypoglycaemia of unknown cause, requiring repeated glucose infusions, subsequently traced to concealed insulin injections used as an ergogenic aid.
Journal of Emergency Medicine - Human1994
Self-induced insulin hypoglycemia in a bodybuilder
One of the earliest published reports of insulin used deliberately for muscle building, documenting self-induced hypoglycaemia. The practice is not new and the case literature is now three decades deep.
Archives of Internal Medicine - Human2014
Prevalence of use of performance enhancing drugs by fitness centre members
718 people across 92 Dutch fitness centres. Direct questioning found 0 to 0.4 percent use of each drug class, while the randomised response technique, designed to elicit sensitive answers, found 8.2 percent overall, with growth hormone and insulin counted as one of the classes. Direct surveys substantially understate use.
Drug Testing and Analysis - Review2014
Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement
Scientific statement noting that most users of performance-enhancing drugs are not competitive athletes but recreational weightlifters, that supraphysiological doses and drug combinations are the norm, and that randomised trials cannot ethically replicate these exposures, so the harm evidence is necessarily observational.
Endocrine Reviews - Review2023
Doping and sports endocrinology: growth hormone, IGF-1, insulin, and erythropoietin
Review covering insulin and erythropoietin among the substances prohibited by the World Anti-Doping Agency, and describing prevalence of use among professional athletes and gym clients, dosing patterns, claimed ergogenic effects, side effects and detection methods.
Revista Clinica Espanola
What users report
Self-reported experiences, not evidence. Nothing below was measured under controlled conditions, and reports like these cannot separate a real effect from placebo, from the training or diet change that accompanied it, or from what the product actually contained. They are here because knowing what people describe, including what goes wrong, is worth reading alongside the studies.
- The practice described in the medical literature is small doses of rapid-acting insulin taken around training or with carbohydrate, usually in combination with growth hormone and anabolic steroids, on the reasoning that insulin drives glucose and amino acids into muscle.
- The presentation that reaches hospital is refractory hypoglycaemia, in the published cases as coma requiring repeated glucose infusions in a young man with no history of diabetes. Emergency physicians are advised in that literature to consider covert insulin use when a healthy weightlifter presents with unexplained low blood sugar.
- Use is substantially under-reported when people are asked directly: in 718 fitness centre members, direct questioning found 0.4 percent overall use of performance-enhancing drugs while an indirect questioning method found 8.2 percent, with growth hormone and insulin counted together as one class.
- The Endocrine Society's assessment is that most users are recreational weightlifters rather than competitive athletes, that doses are frequently supraphysiological, and that drugs are almost always combined, which makes attributing any single harm to insulin alone difficult.
- No published trial has tested insulin for muscle gain or body composition in people without diabetes, so there is no efficacy figure to report for the use these reports describe, only the harms.
Sources: Published medical literature only: the case reports in Journal of Emergency Medicine (2019) and Archives of Internal Medicine (1994), the randomised response prevalence survey in Drug Testing and Analysis (2014), the Endocrine Society scientific statement in Endocrine Reviews (2014), and the 2023 sports endocrinology review in Revista Clinica Espanola. No forum or vendor source is used on this page.
Frequently asked questions
Why is insulin on a peptide database?
Because it is a peptide hormone, it is the reference against which every metabolic drug on this site is judged, and it is misused in exactly the communities that buy peptides. Leaving it out would be a gap, not a neutral choice.
Does insulin cause weight gain?
Yes, and it has been measured. In ORIGIN, 12,537 people followed for a median 6.2 years, median weight rose 1.6 kg on insulin glargine while falling 0.5 kg on standard care. Weight gain is a consistent finding across insulin trials.
How common is severe hypoglycaemia on insulin?
In ORIGIN it was 1.00 event per 100 person-years on insulin glargine against 0.31 on standard care. In DEVOTE, which compared two insulins head to head in 7,637 people, severe hypoglycaemia occurred in 4.9 percent on degludec and 6.6 percent on glargine over the trial.
Is insulin used for muscle building?
It is misused that way, and the published record of it is a case literature of severe hypoglycaemia and coma in bodybuilders rather than any evidence that it builds muscle in healthy people. No randomised trial has tested it for that purpose, and none is likely to be approved. Insulin is prohibited in sport.
Does taking insulin help insulin resistance?
That was tested directly. ORIGIN gave insulin glargine to 12,537 people with dysglycaemia and cardiovascular risk for a median 6.2 years and found cardiovascular outcomes unchanged, with three times as much severe hypoglycaemia and more weight gain than standard care.