Insulin (human insulin)

A hormone the body makes in the pancreas, and one of the earliest medicines based on a protein. The molecule is two separate chains: an A chain of 21 amino acids (GIVEQCCTSICSLYQLENYCN) and a B chain of 30 (FVNQHLCGSHLVEALYLVCGERGFFYTPKT), held together by two sulphur bridges. It therefore cannot be written as a single one-letter sequence; the chain boundaries come from UniProt P01308.

Sold as

Injection under the skin; intravenously in emergency and hospital care, and via an insulin pump.

Legal status in the EU

An approved prescription medicine in the EU and Sweden for decades, both as EU-wide approvals and through national ones. It is covered by the Swedish reimbursement scheme and used in routine care.

It binds the insulin receptor on muscle, fat and liver cells and triggers a chain of signals that pulls glucose out of the blood and into muscle and fat tissue. At the same time it stops the liver making its own glucose and slows the breakdown of fat and protein.

Part of the bodyWhat happensHow it is knownKind of evidence

Blood sugar

This is the whole point of the molecule and it happens within half an hour of an injection under the skin. Insulin docks onto muscle, fat and liver cells and opens the door for glucose to move out of the blood and into them. At the same time it tells the liver to stop releasing the glucose it has stored. Sugar in the blood falls; sugar inside cells rises.

The mechanism is stated in the EU approved labelling. The effect on long-term control was measured in 1,441 people with type 1 diabetes over a mean of 6.5 years, where tighter insulin treatment held average blood sugar (HbA1c) near 7 per cent, and in 3,867 newly diagnosed adults with type 2 diabetes over a median 10 years, where HbA1c was 7.0 per cent on tighter treatment against 7.9 per cent on the looser one.

Measured in people

Source [02]Source [06]Source [07]

The brain, when blood sugar goes too low

The brain runs on glucose and cannot store any, so when insulin pushes blood sugar below what the brain needs, the symptoms come in a fixed order. First the body's alarm system fires: sweating, shaking, a pounding heart, hunger. Then the brain itself starts to run short — confusion, slurred speech, odd behaviour, then seizure or unconsciousness. In people who have had many episodes, the alarm stage stops happening and the first sign is the confusion.

Measured in 1,441 people with type 1 diabetes over a mean 6.5 years: 3,788 episodes of severe low blood sugar, 1,027 of them with coma or seizure. The rate was 61.2 episodes per 100 patient-years on tighter treatment against 18.7 on the looser one, and 65 per cent of the tighter group had at least one episode against 35 per cent. Separately, 27,585 insulin-treated people in 24 countries recorded 73.3 low-blood-sugar events per patient-year in type 1 diabetes and 19.3 in type 2. The loss of warning signs was measured in 518 randomly selected adults with type 1 diabetes, 19.5 per cent of whom had it.

Measured in people

Source [08]Source [09]Source [10]

Body weight, and what the extra weight is made of

People gain weight when insulin treatment is tightened, and it is not a small amount. Part of it is simply that sugar which used to be lost in the urine now stays in the body; part is that insulin tells fat cells to store fat and stops them releasing it. The part the marketing around this molecule never mentions is that the gain is not only fat — the trial that measured it directly found lean tissue in there as well.

Measured in 1,246 adults aged 18 to 39 in the type 1 diabetes trial: the tighter-treatment group gained 4.75 kg more than the looser-treatment group, with BMI rising 1.5 kg/m² more in men and 1.8 kg/m² more in women. In 3,867 adults with type 2 diabetes over a median 10 years, the group assigned insulin gained 4.0 kg against 2.6 kg on one tablet and 1.7 kg on another. In 12,537 people given a laboratory-modified long-acting insulin for a median 6.2 years, weight rose by a median 1.6 kg against a fall of 0.5 kg on standard care.

Measured in people

Source [07]Source [11]Source [12]

The skin and fat where the needle goes in

Inject into the same patch of skin often enough and the fat underneath changes. Most commonly it thickens into a rubbery lump that a person can feel through the skin; less commonly it hollows into a dent. A third change, only recognised more recently, is a deposit of clumped protein under the skin. All three matter for the same reason: insulin injected into altered tissue is absorbed slowly and unpredictably, so the same amount does a different thing on different days. Moving back to normal skin without knowing has caused blood sugar to crash.

Pooled across 16 studies covering 1,722 people who inject insulin, thickened tissue was found in between 14.5 per cent and 88 per cent depending on the study and how it was looked for, with a median of 56.6 per cent. In a separate 316-person study, thickening detectable only by ultrasound scan and not by hand was present in 19.9 per cent. The EU label lists these changes without a frequency and states that a sudden change of injection site to unaffected skin has been reported to cause low blood sugar.

Measured in people

Source [06]Source [13]Source [14]

The eyes

Two opposite things happen on two different clocks. In the first months after control tightens, vision can blur — the lens swells and unswells as the sugar level in it changes — and the small blood vessels at the back of the eye can visibly worsen before they get better. Over years, the same tighter control is the single most effective thing known for stopping diabetic eye disease.

Early worsening at the back of the eye was seen in 13.1 per cent of 711 people on tighter treatment against 7.6 per cent of 728 on looser treatment; it had reversed by the 18-month check in 51 per cent and 55 per cent of them respectively, and none of the cases led to serious loss of vision. Over the trial's mean 6.5 years, tighter treatment cut the appearance of eye disease by 76 per cent in people who had none at the start, and slowed its progress by 54 per cent in those who already had some.

Measured in people

Source [02]Source [15]

Muscle

Insulin does act on muscle protein, which is why it is talked about in gyms — but not in the way the talk suggests. When insulin was raised to normal after-meal levels in healthy men and the arm's protein traffic was measured directly, muscle came out ahead on balance. The reason was that insulin slowed the rate at which existing muscle protein was being broken down. It did not increase the rate at which new muscle protein was built, which stayed where it started.

Measured directly across the forearm in 7 healthy men in a single laboratory study published in 1987. No study has measured what insulin does to muscle in healthy people taking it to build muscle.

One small study

Source [16]

The DCCT trial (NEJM 1993) randomised 1,441 people with type 1 diabetes. Intensive insulin treatment cut the risk of developing eye disease by 76 per cent, slowed the progress of existing eye disease by 54 per cent, reduced clinical nerve damage by 60 per cent and early kidney damage by 39 per cent. The cost was a two- to three-fold increase in severe low blood sugar. The first successful treatment was on 23 January 1922, when Collip's purified extract was given to Leonard Thompson; lab-made human insulin was marketed in 1982 as Humulin and was the first genetically engineered protein approved as a medicine. Insuman has been approved across the EU since 21 February 1997.

Three clocks run at once. The molecule itself is gone from the blood in minutes — its half-life there is about 4 to 6 minutes in healthy people — but its effect on the body long outlasts it. Injected under the skin, plain human insulin starts working within about 30 minutes, peaks between 1 and 4 hours, and is finished after 7 to 9 hours according to the EU label; the US label puts the start at about 30 minutes with a range of 10 to 75, the peak at about 3 hours with a range of 20 minutes to 7 hours, and the end at about 8 hours with a range of 3 to 14. That spread is the reason a low can arrive hours after an injection that seemed fine. The second clock is months: when control is tightened, blurred vision and a temporary worsening of diabetic eye disease appear in the first year, and about half of the eye worsening had reversed by 18 months. The third is years to decades: the reductions in eye, nerve and kidney damage were measured over a mean 6.5 years, the reduction in heart attacks and strokes only became visible at a mean 17 years, and the difference in how many people were still alive appeared at 27.

What was measuredWhat happenedIn whomHow it is known

Diabetic eye disease

Tighter insulin treatment cut the appearance of eye disease by 76 per cent in people who had none at the start (95 per cent confidence interval 62 to 85 per cent), and slowed its progress by 54 per cent in those who already had some (39 to 66 per cent). The severe, sight-threatening form fell by 47 per cent (14 to 67 per cent). The comparison group was people on the standard treatment of the time, one or two injections a day.

1,441 people with type 1 diabetes, 726 with no eye disease at the start and 715 with mild eye disease, mean 6.5 years

Measured in people

Source [02]

Nerve damage

Nerve damage that a doctor could detect on examination fell by 60 per cent against the standard treatment of the time (95 per cent confidence interval 38 to 74 per cent).

The same 1,441 people with type 1 diabetes, mean 6.5 years

Measured in people

Source [02]

Protein leaking into the urine, the first sign of kidney damage

The early form fell by 39 per cent (95 per cent confidence interval 21 to 52 per cent) and the more advanced form by 54 per cent (19 to 74 per cent), both against the standard treatment of the time.

The same 1,441 people with type 1 diabetes, mean 6.5 years

Measured in people

Source [02]

Severe low blood sugar — the cost of the results above

61.2 episodes per 100 patient-years on tighter treatment against 18.7 on the looser one, a rate 3.28 times higher. Episodes with coma or seizure were 3.02 times more common. 65 per cent of the tighter-treatment group had at least one episode, against 35 per cent of the looser group; 22 per cent had multiple episodes within five years, against 4 per cent.

The same 1,441 people with type 1 diabetes, mean 6.5 years

Measured in people

Source [08]

Heart attacks and strokes, measured years after the trial ended

Any cardiovascular event fell by 42 per cent, and the combination of non-fatal heart attack, stroke or death from heart disease fell by 57 per cent (P = 0.02). In numbers: 46 events among 31 people in the tighter-treatment group against 98 events among 52 people in the looser one.

The same 1,441 people with type 1 diabetes, followed a mean of 17 years — 6.5 years of trial and roughly a decade of observation afterwards, during which both groups were treated the same

Measured in people

Source [17]

How many people were still alive after 27 years

43 deaths in the group that had 6.5 years of tighter treatment against 64 in the group that had the standard treatment of the time — a hazard ratio of 0.67, with a range from 0.46 to 0.99 (P = 0.045). The range only just excludes no difference at all, so the result is a modest one and the paper says so.

The same 1,441 people with type 1 diabetes, 27 years from randomisation

Measured in people

Source [18]

Complications of type 2 diabetes

Any diabetes-related endpoint fell 12 per cent (95 per cent confidence interval 1 to 21 per cent, P = 0.029) against diet-first treatment, almost all of it from a 25 per cent fall in small-blood-vessel complications such as needing laser treatment for the eyes (7 to 40 per cent, P = 0.0099). Deaths from diabetes fell 10 per cent and deaths from any cause 6 per cent, and neither result excluded no difference. Insulin did no better and no worse than the two tablets tested alongside it.

3,867 newly diagnosed adults with type 2 diabetes, median age 54, randomised to insulin, one of three sulphonylurea tablets, or diet-first care, median 10 years

Measured in people

Source [07]

Severe low blood sugar and weight in that type 2 diabetes trial

Major low-blood-sugar episodes ran at 1.8 per cent of patients per year on insulin, against 1.4 per cent on one tablet, 1.0 per cent on another and 0.7 per cent on diet-first care. Weight gain was 4.0 kg on insulin against 2.6 kg and 1.7 kg on the tablets.

The same 3,867 adults with type 2 diabetes, median 10 years

Measured in people

Source [07]

Heart attacks and strokes when insulin is added early, in people whose blood sugar is only mildly raised

No difference. 2.94 events per 100 person-years on insulin against 2.85 on standard care for the first main outcome (hazard ratio 1.02, 0.94 to 1.11, P = 0.63), and 5.52 against 5.28 for the wider one (hazard ratio 1.04, 0.97 to 1.11, P = 0.27). Severe low blood sugar was more than three times as common on insulin: 1.00 against 0.31 per 100 person-years. This trial used insulin glargine, a laboratory-modified long-acting insulin, not the human insulin this record covers.

12,537 people with heart risk factors plus raised blood sugar or type 2 diabetes, mean age 63.5, median 6.2 years

Measured in people

Source [12]

Cancer

No difference: hazard ratio 1.00, with a range from 0.88 to 1.13 (P = 0.97). This is the largest direct test of a long-running worry about insulin and cancer, and it came out flat. Again, the insulin tested was glargine and not human insulin.

The same 12,537 people, median 6.2 years

Measured in people

Source [12]

Laboratory-redesigned fast insulins compared against plain human insulin, head to head

Average blood sugar over three months (HbA1c) was 0.13 percentage points lower on the redesigned versions (95 per cent confidence interval 0.10 to 0.16 lower), and blood sugar after meals was 19.44 mg/dl lower — about 1.1 mmol/l. Low blood sugar at night was almost halved (risk ratio 0.55, 0.40 to 0.76) and severe episodes fell by roughly a third (0.68, 0.60 to 0.77). Total episodes barely moved (0.93, 0.87 to 0.99).

22 randomised trials pooling 6,235 people with type 1 diabetes, each comparing a fast-acting redesigned insulin against plain human insulin

Measured in people

Source [19]

Emergency hospital visits caused by insulin itself

About 97,648 emergency department visits a year in the United States were caused by low blood sugar or an insulin error. Almost a third of them, 29.3 per cent, ended in admission to hospital. 60.6 per cent had documented severe neurological effects such as confusion, seizure or loss of consciousness, and blood sugar at or below 50 mg/dl — about 2.8 mmol/l, roughly half normal — was recorded in 53.4 per cent. People aged 80 and over went to emergency departments 2.5 times as often as people aged 45 to 64, and were admitted nearly five times as often. The two most frequent causes were eating less than planned and being given the wrong insulin product.

United States national surveillance data on insulin-treated people of all ages, 2007 to 2011

Measured in people

Source [20]

Low blood sugar is the dominant risk and can be life-threatening; DCCT saw two to three times more severe episodes with intensive treatment. Weight gain and changes to the fat under the skin at injection sites also occur. Insulin is banned in sport and is misused outside healthcare, where the risk of severe low blood sugar is especially high in someone who does not have diabetes.

EffectWhat it feels likeHow often

Low blood sugar severe enough to cause seizure, coma or deathSerious

This is the one that matters. Insulin's dose-response is steep and the amount a person needs changes with food, exercise, illness, alcohol and the injection site. The EU label states that severe episodes, especially repeated ones, can cause lasting damage to the nervous system, and that prolonged or severe episodes can be fatal. About 97,648 emergency department visits a year in the United States were caused by it, 29.3 per cent of them ending in admission.

The EU label gives no frequency at all, and says why: the rate varies so much with the person and the regimen that no single number can be published. The trial and survey figures instead: 61.2 severe episodes per 100 patient-years on tighter treatment in 1,441 people with type 1 diabetes, against 18.7 on looser treatment, with 65 per cent of the tighter group having at least one over 6.5 years. Across 27,585 insulin-treated people in 24 countries, severe episodes ran at 4.9 per patient-year in type 1 diabetes and 2.5 in type 2.

Source [06]Source [08]Source [09]Source [20]

Losing the warning signs that a low is comingSerious

The sweating and shaking that normally announce a low stop happening, so the first sign becomes confusion — by which point the person may not be able to act. The people who had lost their warning signs had six times as many severe episodes in the previous year, an average of 2.36 against 0.38. The EU label names the groups in whom the warning signs fade: people whose control has just been tightened, people whose lows come on gradually, older people, people with long-standing diabetes, people with nerve damage affecting the automatic nervous system, and people taking certain other medicines.

Present in 19.5 per cent of 518 randomly selected adults with type 1 diabetes.

Source [06]Source [10]

Potassium in the blood falling too lowSerious

Insulin drives potassium out of the blood and into cells along with the glucose. Potassium is what makes muscle and heart tissue fire correctly, so if the level in the blood falls far enough the consequences are not subtle: the US label states that untreated low potassium may cause paralysis of the breathing muscles, dangerous heart rhythms and death. It matters most where large amounts of insulin are given quickly, which is hospital and emergency care.

Not measured as a rate in either the EU or the US label.

Source [06]Source [21]

A severe allergic reactionSerious

The EU label names a drop in blood pressure, swelling under the skin, tightening of the airways and a whole-body skin reaction, and states plainly that immediate allergic reactions to insulin or to the other ingredients in the injection may be life-threatening. The US label uses the word anaphylaxis. People allergic to animal insulin may react to human insulin too, which is why skin testing before a switch is written into the label.

Shock is listed as uncommon in the EU label, meaning between 1 in 1,000 and 1 in 100 people. The other immediate allergic reactions are listed with no frequency at all.

Source [06]Source [21]

Heart failure when insulin is combined with pioglitazoneSerious

Pioglitazone is a diabetes tablet that makes the body hold onto fluid. Combined with insulin, which does the same thing, cases of heart failure have been reported — most often in people who already had reasons to be at risk. The label tells doctors to watch for breathlessness, weight gain and swelling, and to stop the tablet if the heart gets worse. The US label carries the same warning for the whole class of these tablets.

Not given as a rate; reported as cases in the EU label.

Source [06]Source [21]

Putting on weight

It is one of the most consistent findings in the whole insulin literature and one of the most common reasons people give for disliking the treatment. The trial that measured body composition rather than just the scales found the extra weight included lean tissue as well as fat.

Measured rather than counted. 4.75 kg more than the comparison group over the trial in 1,246 adults with type 1 diabetes; 4.0 kg over a median 10 years in adults with type 2 diabetes given insulin; a median 1.6 kg over 6.2 years in 12,537 people given a long-acting laboratory-modified insulin, against a fall of 0.5 kg on standard care.

Source [07]Source [11]Source [12]

Swelling from fluid the body holds onto

Insulin makes the kidneys hold onto sodium, and water follows it. The label notes this happens particularly when control that was previously poor is suddenly tightened. It usually shows as puffy ankles or hands.

Listed as common in the EU label, meaning between 1 in 100 and 1 in 10 people.

Source [06]

Lumps, dents and hardened patches where the injections go

Repeated injections into the same patch change the fat underneath — usually a rubbery thickening, sometimes a hollow, sometimes a deposit of clumped protein under the skin. The practical consequence is that insulin injected there is absorbed slowly and unpredictably. The label warns that switching abruptly back to unaffected skin has caused low blood sugar, because the same amount suddenly works properly again.

The EU label lists these without a frequency. Where it has been looked for directly, thickened tissue was found in 14.5 per cent to 88 per cent of people across 16 studies of 1,722 insulin users, median 56.6 per cent; a further 19.9 per cent of 316 people had thickening that only a scan could find.

Source [06]Source [13]Source [14]

Reactions at the injection site

The US label lists bruising, pain, bleeding, redness, small nodules and swelling. The EU label states that most minor reactions clear up on their own within a few days to a few weeks.

Injection site reactions are listed as common in the EU label, meaning between 1 in 100 and 1 in 10 people. Hives at the site are uncommon, between 1 in 1,000 and 1 in 100. Pain, itching, redness, swelling and inflammation at the site are listed with no frequency.

Source [06]Source [21]

Blurred vision when control improves quickly

A sharp change in blood sugar changes how much water the lens of the eye holds, which changes how it focuses. It is temporary and settles as the sugar level steadies. The label separately warns that tightening control abruptly can make existing diabetic eye disease worse for a while before the long-term benefit appears — that happened in 13.1 per cent of 711 people on tighter treatment against 7.6 per cent of 728 on looser treatment, and had reversed in about half of them by 18 months.

Listed in the EU label with no frequency given.

Source [06]Source [15]

Antibodies against the insulin itself

Injected insulin can make the immune system produce antibodies against it. The label says that in rare cases these make the amount needed drift, in either direction, and the dose has to be corrected. It also notes that people who need unusually large amounts because of these antibodies should be switched between insulins in hospital.

Listed in the EU label with no frequency given.

Source [06]

These are the amounts the studies below gave their participants, and they are here as facts about those studies. They are not a recommendation, not a starting point and not a range to pick from. What a person should take, if anything, is a question for a doctor who knows them.

The DCCT, the trial behind almost everything known about insulin in type 1 diabetes. No fixed amount was used: each person's dose was set individually and adjusted continually against blood-sugar readings, so what the trial tested was two ways of delivering insulin rather than two amounts of it.

Tighter treatment: a pump worn on the body, or three or more injections a day, guided by frequent blood-glucose testing. Standard treatment of the time: one or two injections a day.

A mean of 6.5 years in 1,441 people; the same people were then followed for 27 years in total

Source [02]Source [18]

UKPDS 33, in newly diagnosed type 2 diabetes. Again no fixed amount: the insulin arm's dose was set for each person and adjusted towards a fasting blood-sugar target the trial had defined in advance.

Insulin injections, amount individual and adjusted throughout, compared against three sulphonylurea tablets and against diet-first care

A median of 10 years in 3,867 adults

Source [07]

ORIGIN, which tested whether adding insulin early prevents heart attacks. The insulin used was glargine, a laboratory-modified long-acting version and not the human insulin this record covers.

Insulin glargine once a day, amount individual and adjusted towards the trial's fasting blood-sugar target of 95 mg/dl (5.3 mmol/l), against standard care

A median of 6.2 years in 12,537 people

Source [12]

The pooled head-to-head trials of plain human insulin against the faster laboratory-redesigned versions, which is the comparison that decides which insulin a person is prescribed today. None of the 22 trials fixed an amount either.

Plain human insulin injected before meals, against a fast-acting redesigned insulin injected before meals, each adjusted individually

22 randomised trials pooling 6,235 people with type 1 diabetes

Source [19]

What people report

• What any specific amount of insulin does — no published trial ever fixed a dose, because every one of them adjusted the amount person by person against a blood-sugar target, so there is no study that says what a given amount does to a given person
• How often severe low blood sugar happens on insulin overall — the EU label states outright that no specific frequency can be presented, because the rate depends entirely on the person and the regimen
• What insulin does to muscle in healthy people using it to build muscle — never studied; the only direct human muscle measurement is 7 healthy men in a single 1987 laboratory study
• How much of the weight gained on insulin is fat and how much is lean tissue, in numbers — the trial that looked concluded only that lean tissue was in there too
• What happens over more than about 30 years of continuous use — the DCCT/EDIC follow-up at 27 years is the longest randomised evidence that exists for any insulin
• Whether plain human insulin affects the heart, either way — the trial that tested insulin against heart attacks used a laboratory-modified long-acting version in people who mostly did not have type 1 diabetes
• Whether the thickened patches at injection sites do anything beyond making absorption unpredictable — the studies counted how many people have them, not what happens to those people afterwards
• How often insulin causes a serious allergic reaction — the EU label puts shock at somewhere between 1 in 1,000 and 1 in 100 and gives no frequency at all for the other immediate allergic reactions
• How often anti-insulin antibodies matter — the label says they form and can make the required amount drift in either direction, and gives no rate
• Whether human insulin is safe in pregnancy on trial evidence — the EU label states there are no clinical data on exposed pregnancies for human insulin, only the observation that it does not cross the placenta
• What happens to people who use it without diabetes over months or years — the published record is individual case reports of coma and intensive care, not a study of anything
• What happens to blood sugar control when people take less insulin than prescribed because they cannot afford it — a quarter of one surveyed group said they had, and no trial has measured the consequence

Bodybuilders use it to build muscle. Does that actually work?

Nobody has measured it. There is no published study of insulin for muscle gain in healthy people. The one direct human measurement of what insulin does to muscle protein was made in 7 healthy men in 1987: insulin slowed the breakdown of muscle protein that was already there, and did not increase the building of new protein at all — the building rate stayed exactly where it started. What is documented is the harm. Published case reports describe a 30-year-old bodybuilder brought to hospital comatose from insulin he had concealed, and another who injected 70 units before a competition and had convulsions, needing a breathing tube and intensive care. Insulin is on the World Anti-Doping Agency's prohibited list.

Source [16]Source [22]Source [23]

What happens if someone with type 1 diabetes stops taking it?

Without insulin the body cannot use sugar at all and starts burning fat instead, producing acids that poison the blood. This is diabetic ketoacidosis, and it develops over hours to days. There were 1,760,101 hospital admissions for it in the United States between 2003 and 2014, rising from 118,808 a year to 188,965 a year, and 0.4 per cent of those admissions ended in death in hospital — 7,031 people. In one hospital series, treatment not being taken was the precipitating cause in 39 per cent of all cases and 49 per cent of those already diagnosed with type 1 diabetes. The EU label states that people with type 1 diabetes must never omit insulin entirely, even when illness means they can eat little or nothing.

Source [06]Source [24]Source [25]

Does insulin make you fat, and is the extra weight fat or muscle?

It makes people heavier, reliably, and the trials disagree with the simple story that all of it is fat. In 1,246 adults aged 18 to 39 with type 1 diabetes, the tighter-treatment group gained 4.75 kg more than the comparison group, and the paper that measured body composition rather than just the scales concluded that the extra weight appeared to include lean tissue as well as fat. In 3,867 adults with type 2 diabetes over a median 10 years, the insulin group gained 4.0 kg against 2.6 kg and 1.7 kg on tablets. In 12,537 people given a long-acting laboratory-modified insulin for a median 6.2 years, weight rose a median 1.6 kg while the comparison group lost 0.5 kg.

Source [07]Source [11]Source [12]

Does insulin cause cancer?

The largest trial that set out to check found no sign of it. 12,537 people were randomised to a long-acting insulin or to standard care and followed a median 6.2 years; the rate of cancer came out at a hazard ratio of 1.00, with a range from 0.88 to 1.13 — as flat a result as this kind of comparison produces. The insulin tested was glargine, a laboratory-modified version rather than plain human insulin, and 6.2 years is not a lifetime.

Source [12]

Human insulin is the cheap one. Are the newer laboratory-redesigned insulins actually better?

A little better, and mostly on lows rather than on control. Pooling 22 randomised trials of 6,235 people with type 1 diabetes, the fast-acting redesigned versions gave an average blood sugar 0.13 percentage points lower than plain human insulin, and blood sugar after meals about 1.1 mmol/l lower. The clearer difference was at night: lows during sleep were nearly halved (risk ratio 0.55) and severe lows fell by about a third (0.68). The total number of lows barely moved.

Source [19]

Is a low blood sugar episode actually dangerous, or just unpleasant?

Both, depending on how far it goes. Around 97,648 emergency department visits a year in the United States were caused by insulin-related lows or insulin errors; 29.3 per cent ended in admission to hospital, 60.6 per cent had documented severe effects on the nervous system such as confusion, seizure or loss of consciousness, and blood sugar at or below about half the normal level was recorded in 53.4 per cent. The EU label states that severe episodes, especially repeated ones, may lead to lasting damage to the nervous system, and that prolonged or severe episodes may be life-threatening. The two commonest triggers in the emergency data were eating less than planned and being given the wrong insulin product.

Source [06]Source [20]

1. [01]UniProt P01308 – Insulin, Homo sapiens (signalpeptid 1–24, B-kedja 25–54, A-kedja 90–110)
2. [02]The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus (DCCT), NEJM (1993)
3. [03]100 Years since the Discovery of Insulin, from Its Discovery to the Insulins of the Future, Biomedicines (2024)
4. [04]EMA – Insuman (insulin human), EPAR: approved 21/02/1997 (1997)
5. [05]WADA International Standard Prohibited List 2026, S4.4.2 Insulins and insulin-mimetics (2026)
6. [06]European Medicines Agency — Insuman (insulin human), product information, section 5.1 mechanism of action and 5.2 pharmacokinetics
7. [07]UKPDS 33: intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes, The Lancet (1998)
8. [08]Hypoglycemia in the Diabetes Control and Complications Trial, Diabetes (1997)
9. [09]Rates and predictors of hypoglycaemia in 27,585 people from 24 countries with insulin-treated type 1 and type 2 diabetes: the global HAT study, Diabetes, Obesity and Metabolism (2016)
10. [10]Prevalence of impaired awareness of hypoglycaemia in adults with type 1 diabetes, Diabetic Medicine (2008)
11. [11]Influence of intensive diabetes treatment on body weight and composition of adults with type 1 diabetes in the DCCT, Diabetes Care (2001)
12. [12]ORIGIN: basal insulin and cardiovascular and other outcomes in dysglycemia, New England Journal of Medicine (2012)
13. [13]A systematic review of ultrasound-detected lipohypertrophy in insulin-exposed people with diabetes, Diabetes Therapy (2018)
14. [14]Subclinical lipohypertrophy — easily ignored complications of insulin therapy, Journal of Diabetes and its Complications (2021)
15. [15]Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial, Archives of Ophthalmology (1998)
16. [16]Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man, Journal of Clinical Investigation (1987)
17. [17]Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes (DCCT/EDIC), New England Journal of Medicine (2005)
18. [18]Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality (DCCT/EDIC), JAMA (2015)
19. [19]Short-acting insulin analogues versus regular human insulin on postprandial glucose and hypoglycemia in type 1 diabetes mellitus: a systematic review and meta-analysis, Diabetology & Metabolic Syndrome (2019)
20. [20]National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations, JAMA Internal Medicine (2014)
21. [21]DailyMed — HUMULIN R (insulin human injection), US prescribing information, section 5 warnings and precautions
22. [22]Severe hypoglycemia due to cryptic insulin use in a bodybuilder, Journal of Emergency Medicine (2019)
23. [23]Insulin as an anabolic: hypoglycaemia in the bodybuilding world, Anästhesiologie Intensivmedizin Notfallmedizin Schmerztherapie (1998)
24. [24]Health care utilization and burden of diabetic ketoacidosis in the US over the past decade: a nationwide analysis, Diabetes Care (2018)
25. [25]Precipitating factors of diabetic ketoacidosis at a public hospital in a middle-income country, Diabetes Research and Clinical Practice (2012)