Insulin dosage and evidence

What is Insulin?

How does Insulin work?

In people, insulin docks on the insulin receptor. That pushes sugar into muscle and fat. It stops the liver pouring out sugar. It helps store sugar and fat, and it stops fat breaking down. At high levels it also switches on the IGF-1 receptor. That is the basis for the muscle-building claims made by people who misuse it. It is also why those doses are dangerous. The risk of low blood sugar comes straight from how it works. Once injected, the dose cannot be taken back. And people who have had diabetes a long time have weaker defences against a low.

What have studies in people found about Insulin?

The deepest record of any peptide on this site. Tens of thousands of people over decades, with long follow-up. It proves the benefit in diabetes. It also measures the two costs, low blood sugar and weight gain, in hard numbers.

• ORIGIN: 12,537 people got insulin glargine or usual care. Heart events were about the same. Dangerous lows were more than three times as common (1.00 against 0.31 per 100 people per year). Typical weight went up 1.6 kg against down 0.5 kg. No cancer signal. Sanofi paid.
• DEVOTE: 7,637 people, degludec against glargine. Heart safety was about equal. Dangerous lows hit 4.9 against 6.6 percent, a real difference between two insulins. Novo Nordisk paid.
• UKPDS 33, type 2 diabetes: 3,867 newly diagnosed people. Typical HbA1c was 7.0 against 7.9 percent over 10 years. There were fewer small blood vessel problems, and more low blood sugar, on tight treatment.
• UKPDS 10 year follow-up: the benefits lasted after the blood sugar gap vanished. The pill-or-insulin group had 15 percent fewer heart attacks and 13 percent fewer deaths. This is usually called the legacy effect.
• DCCT/EDIC, type 1 diabetes: 1,441 people, followed for 17 years. Tight insulin treatment cut heart events of any kind by 42 percent, and heart attacks, strokes and heart deaths together by 57 percent.
• Misuse: case reports since 1994 describe coma and hard-to-fix low blood sugar in bodybuilders using insulin to build muscle. A survey of 718 gym members found 8.2 percent used performance drugs when asked in a way that protected their privacy. Asked directly, only 0.4 percent said yes.

What this does not tell you: None of these studies tested insulin in people without diabetes or blood sugar problems. None tested it for muscle, body shape or longer life. The diabetes studies show what happens when insulin is used to control blood sugar in people who need it. Their heart findings are about blood sugar control as much as about insulin itself. The misuse evidence is case reports and surveys. It shows that serious harm happens and roughly how common use is. It cannot put a number on the risk per shot, or say what dose someone can survive.

What do people who took Insulin report?

This is what real people say happened to them, good and bad. Nobody measured it. A report cannot tell a real effect from the lift people get just from expecting it to work, from a diet or training change made at the same time, or from what was really in the vial. We still put it near the top. It is the next best thing to a study in people: what happens when real people use it, including what goes wrong.

• The practice described in medical papers is small doses of fast-acting insulin around training or with carbs. It is usually stacked with growth hormone and steroids. The idea is that insulin drives sugar and protein building blocks into muscle.
• What reaches the hospital is low blood sugar that will not stay fixed. In the published cases, it is a young man with no diabetes in a coma, who needs sugar by drip again and again. Those papers advise emergency doctors to think of hidden insulin use when a healthy weightlifter shows up with unexplained low blood sugar.
• People badly under-report it when asked straight out. Among 718 gym members, direct questions found 0.4 percent used performance drugs. A method that protected their privacy found 8.2 percent. Growth hormone and insulin were counted together as one group.
• The Endocrine Society says most users are gym-goers, not competing athletes. Doses are often far above what the body makes, and drugs are almost always stacked. That makes it hard to blame any one harm on insulin alone.
• No published study has tested insulin for muscle gain or body shape in people without diabetes. So there is no benefit figure to report for this use. There are only the harms.

Sources: Published medical literature only: the case reports in Journal of Emergency Medicine (2019) and Archives of Internal Medicine (1994), the anonymous 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.

The state of the research

The evidence, in charts

The studies we cite

• Study in people2005
  Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes

  Tight blood sugar control early on protected hearts for decades afterwards. 1,441 people with type 1 diabetes got either tight or standard insulin treatment for about six and a half years, then were simply followed. Over about 17 years, the tight group had roughly 42 percent fewer heart events of any kind. Heart attacks, strokes and deaths from heart disease together fell by about 57 percent. The tight treatment had ended long before the benefit showed up.

  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).

  PMID 16371630 New England Journal of Medicine
• Study in people1998
  Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

  Controlling blood sugar tightly protected the small blood vessels, and it came at a cost. 3,867 people newly diagnosed with type 2 diabetes got either tight treatment with insulin or sulfonylurea pills, or diet-first care. Over 10 years their typical long-term blood sugar ran 7.0 against 7.9 on the usual scale. Damage to eyes, kidneys and nerves was less common in the tight group. Blood sugar dropping too low was more common. This tested tight control, not insulin against pills.

  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.

  PMID 9742976 Lancet
• Study in people2008
  10-year follow-up of intensive glucose control in type 2 diabetes

  The benefit of early tight control outlasted the control itself. 4,209 people from the original trial were followed for 10 more years. Within a year of the trial ending, blood sugar in the two groups had evened out. Ten years later the intensively treated group still had fewer diabetes complications, fewer heart attacks and fewer deaths of any cause. Those treated with metformin did better still. Once the trial ended nobody was assigned to anything, so this part is observation rather than a test.

  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).

  PMID 18784090 New England Journal of Medicine
• Study in people2012
  Basal insulin and cardiovascular and other outcomes in dysglycemia

  Giving long-acting insulin early did not protect the heart, and it did not cause cancer either. 12,537 people with heart risk factors and blood sugar problems got insulin glargine or usual care, then were followed for about six years. Heart outcomes came out the same. Blood sugar dropping dangerously low was about three times more common on insulin. People on insulin gained about 1.6 kg while the others lost half a kilo. Sanofi, which sells the insulin, paid for it.

  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.

  PMID 22686416 New England Journal of Medicine
• Study in people2017
  Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes

  Two long-acting insulins protected the heart equally, and one caused fewer dangerous lows. 7,637 people with type 2 diabetes, most already with heart or kidney disease, got degludec or glargine without knowing which. Major heart events happened in 8.5 percent against 9.3 percent, close enough to call equal. Severe low blood sugar hit 4.9 percent against 6.6 percent, about 17 fewer people in every thousand. Novo Nordisk, which sells degludec, paid for it.

  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.

  PMID 28605603 New England Journal of Medicine
• Study in people2019
  Severe Hypoglycemia Due to Cryptic Insulin Use in a Bodybuilder

  One man nearly died using insulin to build muscle. A 30 year old bodybuilder arrived in hospital in a coma with dangerously low blood sugar and no explanation. He needed glucose through a drip, again and again, to bring him round. The cause turned out to be insulin he had been injecting and hiding. This is a single case report. It tells you what can happen, not how often it happens.

  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.

  PMID 30527564 Journal of Emergency Medicine
• Study in people1994
  Self-induced insulin hypoglycemia in a bodybuilder

  People have been doing this since at least the early 1990s. This report describes a bodybuilder who injected insulin deliberately to gain muscle and drove his own blood sugar dangerously low. It is one of the first accounts of the practice in a medical journal. Three decades of similar case reports have followed. A pile of single cases shows that a pattern exists. It does not measure how common or how dangerous the practice is.

  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.

  PMID 8285818 Archives of Internal Medicine
• Study in people2014
  Prevalence of use of performance enhancing drugs by fitness centre members

  Ask people directly and they deny it. Ask them safely and they admit it. 718 people at 92 Dutch gyms were surveyed about performance enhancing drugs, with growth hormone and insulin among the categories counted. Asked outright, almost nobody said yes. Asked through a method built to protect their anonymity, 8.2 percent did. Survey answers are still only answers, and nobody was tested. The lesson is that direct questions badly understate what is going on in gyms.

  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.

  PMID 24019293 Drug Testing and Analysis
• Review of studies2014
  Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement

  A statement from the Endocrine Society. Most people who use performance drugs are gym-goers, not competing athletes. They usually take doses far above normal and stack several drugs. Proper studies cannot ethically copy that, so the harm evidence has to come from watching people.

  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.

  PMID 24423981 Endocrine Reviews
• Review of studies2023
  Doping and sports endocrinology: growth hormone, IGF-1, insulin, and erythropoietin

  A review of insulin and erythropoietin among the drugs banned in sport. It covers how common use is among pro athletes and gym-goers, how people dose, what they claim it does, the side effects, and how testers catch it.

  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.

  PMID 36736729 Revista Clinica Espanola