What Is Insulin?

1. What is insulin and how does it work?

The human hormone is built from two linked peptide chains, with a molecular weight near 5.8 kDa. The Humulin R label describes it as produced by a non-pathogenic laboratory strain of E. coli. For background on how peptide drugs differ from small molecules, see the peptide explainer.

The labels describe one shared action. Insulin lowers glucose by:

• raising glucose uptake into skeletal muscle and fat tissue;
• holding back glucose output from the liver;
• slowing the breakdown of fat (lipolysis) and protein (proteolysis) while supporting protein synthesis.

It also drives potassium from the blood into cells. That is why every label carries a warning about hypokalemia, meaning low blood potassium.

Insulin’s partner hormone is glucagon, which raises blood sugar; glucagon also appears in the labels as a treatment for severe hypoglycemia. GLP-1 drugs act on a different system, the incretin hormones, rather than replacing insulin directly. Insulin is also distinct from insulin-like growth factor 1; see IGF-1 LR3 for that pathway.

2. What are the different types of insulin?

Analogs carry small amino-acid changes or formulation tricks that alter absorption, not what insulin does once it reaches the blood. NPH is human insulin crystallized with protamine and zinc. Glargine is formulated at a pH of about 4 for slow, prolonged absorption, and degludec carries a fatty-acid side chain that forms a slow-release depot and binds albumin (Tresiba label).

The labels group them by timing after a subcutaneous injection, while warning that timing varies widely with injection site, blood flow, temperature, exercise and dose.

Sources: NovoLog, Humalog, Humulin R, Humulin N, Lantus and Tresiba labels.

Half-life versus duration

A subcutaneous insulin’s half-life mostly reflects how slowly it leaves the injection depot, not how fast the liver and kidneys clear it. The labeled apparent half-life is about 1 hour for lispro, 81 minutes for aspart, about 1.5 hours for regular insulin, about 4.4 hours for NPH and about 25 hours for degludec. Degludec is over 99% bound to albumin and reaches steady state after 3–4 days.

Duration can stretch well past these figures. The Humulin R label reports that in obese subjects given large doses, regular insulin acted for about 18 hours instead of about 8. A half-life model can show a concentration curve, but it cannot predict the glucose effect for an individual.

How doses are set

Labels give no fixed dose. They tell prescribers to individualize insulin from blood glucose monitoring, metabolic needs and treatment goals, and to change any regimen only under close medical supervision. Most products are 100 units/mL (U-100), with some concentrated versions.

3. What does the clinical evidence show?

The strongest outcome evidence comes from type 1 diabetes. The Diabetes Control and Complications Trial (DCCT) randomized 1,441 patients to intensive or conventional insulin therapy for a mean of 6.5 years.

The last row is the key to insulin therapy. Tighter control prevented eye, kidney and nerve damage, and in the same patients it increased severe low blood sugar. Every later decision about adding drugs to insulin, including GLP-1 drugs, works within that trade-off.

4. What happens when a GLP-1 drug is combined with insulin?

Insulin labels list other diabetes drugs among the medicines that raise hypoglycemia risk (Humalog label). The GLP-1 labels state this directly. The Ozempic label warns that people taking semaglutide with insulin or a sulfonylurea may have a higher risk of hypoglycemia, including severe hypoglycemia. Its drug-interaction section says to consider reducing the insulin dose when starting the GLP-1 drug. The Mounjaro label gives the same warning and advice for tirzepatide.

The label trial numbers

Both labels report a placebo-controlled trial in which the GLP-1 drug was added to basal insulin, with or without metformin. Placebo groups stayed on insulin too, so their rates show the background risk from insulin alone.

Two cautions apply. These were supervised trial populations, and the two labels use different glucose thresholds, so the rows cannot be compared head to head. The pattern is still clear: adding a GLP-1 drug to insulin raised hypoglycemia, most visibly in milder documented episodes on the higher semaglutide dose.

Fixed-ratio insulin and GLP-1 pens

Two products put both drugs in one pen. Soliqua combines insulin glargine with lixisenatide (Soliqua label), and Xultophy combines insulin degludec with liraglutide (Xultophy label). Both labels list hypoglycemia among their warnings and advise against using them with another GLP-1 receptor agonist. Adding Ozempic or Mounjaro on top of one of these pens would therefore run against both labels.

Why reduced eating matters

GLP-1 drugs reduce appetite. The insulin labels list skipped or delayed meals and changes in carbohydrate intake as triggers for hypoglycemia, and a CDC analysis found that reduced food intake was among the most common causes of insulin-related emergency visits (Geller et al., 2014). The labels do not quantify this interaction for GLP-1 users, but it explains why dose reviews during dose titration matter.

5. Does insulin build muscle or prevent muscle loss on GLP-1 drugs?

The best human evidence is a 2016 meta-analysis of insulin infusion studies, pooling 25 studies and 173 people (Abdulla et al.).

The authors described insulin’s role in synthesis as permissive: it helps only when amino acids are available. These were short, controlled clamp studies in which glucose was infused alongside insulin to prevent hypoglycemia, conditions that do not exist after a self-administered injection.

No randomized trial has tested injected insulin for muscle size, strength or performance in healthy or trained people. Nor has any trial tested insulin as a way to protect lean mass during GLP-1 weight loss. The GLP-1 muscle loss guide covers what has actually been measured in that setting. Claims that insulin adds muscle rest on protein-turnover physiology, not outcome data.

6. What are the side effects of insulin?

Hypoglycemia

According to the labels, severe hypoglycemia can cause seizures and unconsciousness and can be fatal. It can also slow thinking and reaction time, for example while driving. Risk peaks when the insulin’s effect is at its maximum and rises with changes in meals, physical activity or other medicines, and with kidney or liver impairment. Warning symptoms can fade after repeated episodes, with long-standing diabetes, with nerve damage and with beta-blockers.

The American Diabetes Association’s 2026 Standards of Care grade hypoglycemia as follows.

Severe events occur even under supervision. In the Lantus label trials, severe symptomatic hypoglycemia affected 6.5–10.6% of adults with type 1 diabetes on glargine over 16–28 weeks, and 23.0% of children with type 1 diabetes over 26 weeks. In the ORIGIN trial, which followed adults with cardiovascular disease or risk factors for a median 6.2 years, the figure was 5.6% on glargine versus 1.8% on standard care.

Nationally, a CDC study estimated 97,648 US emergency department visits a year for insulin-related hypoglycemia and insulin errors in 2007–2011 (Geller et al.). Nearly 3 in 10 led to hospital admission, and over half involved a glucose of 50 mg/dL or lower. Injecting the wrong insulin product was another leading cause.

Other label warnings

• Low potassium. Untreated hypokalemia can cause breathing paralysis, dangerous heart rhythms and death, per the Humalog label.
• Allergy. Severe whole-body reactions, including anaphylaxis, can occur.
• Injection-site changes. Repeated injections in one spot can thicken or thin fat tissue or cause amyloid deposits. Absorption from those areas is reduced, and moving to fresh skin can then trigger hypoglycemia.
• Weight gain and swelling. Both are listed reactions; with thiazolidinediones, fluid retention can worsen heart failure.
• Shared pens. Sharing pens, needles or syringes can spread blood-borne infections.

Insulin is contraindicated during a hypoglycemic episode and in people allergic to the product.

Other drug interactions

The Humalog label also lists medicines that blunt insulin’s effect, including corticosteroids, diuretics, estrogens, thyroid hormone and somatropin. Growth hormone therefore pushes glucose in the opposite direction from insulin. Alcohol, beta-blockers, clonidine and lithium can raise or lower the effect, and several of these also mask hypoglycemia symptoms.

7. What happens in an insulin overdose?

The labels say excess insulin can cause hypoglycemia and hypokalemia, that severe episodes may need glucagon or intravenous glucose, and that hypoglycemia can return after apparent recovery (Humulin R label). Published data show a wide range of outcomes.

In the large-overdose review, some patients needed intravenous glucose for up to a week. That persistence is why a single correction of low blood sugar does not end the danger.

8. Is insulin legal, and why do athletes misuse it?

In the US, insulin is not a Schedule III controlled substance (21 CFR 1308.13). Analogs need a prescription, while Humulin R U-100 and Humulin N have over-the-counter labels. WADA’s 2026 Prohibited List bans insulins and insulin-mimetics at all times under S4.4.2, as non-Specified substances.

What surveys and case reports show

In a 2009 online survey, researchers described 41 strength athletes without diabetes who used insulin (Ip et al., 2012). Of these, 95.1% also used anabolic steroids, 56.8% reported hypoglycemia, and one reported losing consciousness. Among 92 recreational bodybuilders in an Italian study, 43% regularly used hormones, and 38% of those used insulin; insulin use was tied to a higher ALT-to-AST liver enzyme ratio (Di Girolamo et al., 2024).

Case reports describe young, otherwise healthy men with severe hypoglycemia. A Swiss bodybuilder had seizures and needed intubation after injecting short-acting insulin before a competition (Konrad et al., 1998). A French bodybuilder arrived in a coma later traced to hidden insulin injections (Heidet et al., 2019). UK clinicians noted in 2003 that part of insulin’s appeal was that tests of the time could not detect it (Evans and Lynch).

That is no longer true for analogs. Anti-doping labs have validated methods that identify lispro, aspart, glulisine, a glargine metabolite and degludec in urine (Thomas et al., 2021). Unmodified human insulin is a tougher case, because it matches what the pancreas makes.

9. What can you meaningfully measure or track?

Glucose is the measurement that matters, because the labels base every dose decision on glucose monitoring and define hypoglycemia by it. The ADA levels above give a shared language for logging readings and talking with a clinician.

Alongside readings, a useful record includes:

• the exact insulin product and dose, since injecting the wrong product was a leading cause of emergency visits;
• meal timing and size, especially once a GLP-1 drug reduces appetite;
• exercise, alcohol and illness, all listed hypoglycemia triggers;
• the start date and every dose step of any GLP-1 drug, so glucose changes can be lined up with titration;
• injection sites, because repeated use of one area can change absorption.

A log cannot tell anyone how much to change an insulin dose; that decision belongs to the prescriber. It can show when lows cluster after a meal change, a workout or a new GLP-1 dose, which makes that conversation faster and more precise. The GLP-1 tracker guide describes ways to keep these entries together.

10. Insulin FAQ

• Can insulin be used with semaglutide or tirzepatide?

  Yes, in type 2 diabetes. Both the Ozempic and Mounjaro labels include trials of the drug added to basal insulin, and fixed-ratio pens such as Soliqua and Xultophy combine a basal insulin with a GLP-1 drug. The Ozempic and Mounjaro labels warn that the combination increases the risk of hypoglycemia, including severe hypoglycemia, and say prescribers should consider reducing the insulin dose when the GLP-1 drug is started. Any dose change belongs with the prescribing clinician.

• What are the side effects of insulin?

  Hypoglycemia is the most common adverse reaction on every insulin label. Labels also list low blood potassium, allergic reactions including anaphylaxis, changes in fat tissue at repeated injection sites, weight gain and swelling. Fluid retention and heart failure are a particular concern when insulin is combined with thiazolidinediones.

• How long does insulin stay in your system?

  It depends on the product. Labeled apparent half-lives are about 1 to 1.5 hours for subcutaneous lispro, aspart and regular insulin and about 25 hours for degludec at steady state. The glucose-lowering effect can last much longer than the half-life suggests: about 3–5 hours for aspart, about 8 hours for regular insulin (about 18 hours with large doses in obese subjects) and at least 42 hours for degludec.

• Is insulin legal to buy?

  In the US, insulin analogs such as lispro, aspart, glargine and degludec are prescription-only. Humulin R U-100 and Humulin N are published with over-the-counter labels. Insulin is not a controlled substance under Schedule III. Legal access does not make non-medical use safe.

• Does insulin build muscle?

  A 2016 meta-analysis of infusion studies found that insulin reduces muscle protein breakdown and supports protein synthesis only when amino acid supply is raised. No randomized trial has tested injected insulin for muscle size, strength or performance in healthy people.

• Is insulin banned in sport?

  Yes. WADA lists insulins and insulin-mimetics under S4.4.2 as prohibited in and out of competition. Validated mass-spectrometry methods can detect synthetic analogs such as lispro, aspart, glargine and degludec in urine.

• What blood sugar level counts as hypoglycemia?

  The American Diabetes Association defines level 1 as glucose under 70 mg/dL but at least 54 mg/dL, level 2 as under 54 mg/dL, and level 3 as a severe event with altered mental or physical status that needs another person's help, at any glucose level.

• What happens if someone takes too much insulin?

  Excess insulin causes hypoglycemia and low potassium. Labels warn that hypoglycemia can return after apparent recovery. In a review of 45 published large overdoses, hospital stays had a median of 94 hours and one-third of patients needed intensive care. Suspected overdose is an emergency.

11. Sources