Insulin is a unique case in anti-doping: it is both a prohibited substance and a vital drug for some athletes, particularly Olympians with type 1 diabetes. How does the World Anti-Doping Agency reconcile these two realities? The editors explain exactly where insulin is placed on the Prohibited List, how the therapeutic use authorization procedure works, and what is known about the detection of insulin in samples.
Where is insulin on the Prohibited List
In the current WADA Prohibited List, insulins belong to section S4 "Hormonal and metabolic modulators", a subgroup of metabolic modulators. The wording covers "insulins and insulin mimetics" — that is, not only human insulin and its analogs, but also substances that mimic the action of the hormone on the receptor.
S4 substances are prohibited at all times - both during and outside the competition. This means that a positive insulin test is a violation regardless of whether it is taken at a tournament, during out-of-competition testing at home or at a training camp.
Nearby in the same section are other metabolic modulators such as AMPK activators, meldonium, and trimetazidine, as well as aromatase inhibitors, antiestrogens, and myostatin modulators. A related but distinct case is insulin-like growth factor 1 (IGF-1) and its analogs—they are classified in section S2 along with growth hormone.
| Parameter | Insulin on the Prohibited List |
|---|---|
| Section | S4 — Hormonal and metabolic modulators (metabolic modulators) |
| Formulation | Insulins and insulin mimetics |
| When prohibited | At all times: in and out of competition |
| Possibility of TUE | Yes, with a confirmed medical indication (mainly diabetes) |
The numbering of subdivisions and details of wording in the list may change from year to year, so athletes and team doctors should always consult the current edition of the document, which comes into force on January 1.
History of the ban
Interest in insulin among athletes increased significantly in the 1990s, primarily in strength sports and bodybuilding. The International Olympic Committee banned insulin in 1998, after which the ban moved to WADA's Prohibited List when the agency took over its administration.
The reasons for the ban meet the general criteria of the World Anti-Doping Code: potential for performance enhancement (as perceived by athletes), risk to health and unsportsmanlike conduct. For a substance to be listed, it is sufficient that it meets two of the three criteria.
In the case of insulin, the health risk criterion is particularly important. Severe hypoglycemia can cause coma and death, and the medical literature has reported such cases among bodybuilders. Professor Peter Sonksen in his review (2001) also emphasized that the uptake of insulin among athletes is outpacing the available evidence of benefit.
During the 2000s, anti-doping laboratories developed methods to detect synthetic analogues of insulin, and this work continues. One of the leading research centers in this field is a laboratory in Cologne (Germany), whose researchers, including Mario Tevis, have published a number of reviews and methodological works.
Athletes with diabetes: authorization for therapeutic use
For an athlete with type 1 diabetes, insulin is a vital therapy, and the anti-doping system recognizes this. Such an athlete may receive a Therapeutic Use Exemption (TUE) in accordance with the International TUE Standard. The history of sports knows many Olympic champions and professionals who competed with type 1 diabetes, using insulin legally.
To obtain a TUE, four conditions must be proven: the presence of a confirmed medical condition that requires treatment; unlikely that treatment will provide additional improvement in outcome beyond return to normal health; no reasonable permitted alternative; and that the need is not the result of prior use of prohibited substances.
- Documents confirming the diagnosis: medical history, date of diagnosis, examination results.
- Laboratory data, such as glycated hemoglobin, C-peptide level, autoantibodies (for type 1 diabetes).
- Description of the treatment regimen prescribed by the doctor and information about glucose monitoring devices.
- Application on a standard form submitted to a national anti-doping organization or an international federation.
WADA publishes separate TUE Physician Guidelines for diabetes (TUE Physician Guidelines — Diabetes Mellitus). They describe what documents are usually expected. In type 2 diabetes, when insulin is prescribed after the failure of other drugs, the application must show that insulin is really needed clinically.
It is important to apply in advance. Retroactive TUE is possible only in cases defined by the International Standard, for example in case of urgent care, and should not be counted on as a routine procedure.
How insulin is detected in samples
Detection of insulin is one of the most difficult tasks for anti-doping laboratories. The hormone has a short half-life, is naturally present in the body, and its concentrations in urine are low. However, the methods have improved significantly over the past two decades.
Synthetic analogues of insulin — lispro, aspart, glulisine, glargine, detemir, degludec — have a changed structure, so liquid chromatography with tandem mass spectrometry (LC-MS/MS) can distinguish them from the endogenous hormone. The methods described in the work of the Tevis group allow identification of analogues and their metabolites in urine and blood.
Human recombinant insulin is more difficult because it is identical to one's own. Indirect approaches are used here: endogenous insulin is released together with C-peptide in equal amounts, while exogenous insulin is released without it. Disproportionately high insulin on the background of low C-peptide in the blood is used in clinical medicine as a sign of external insulin administration.
In addition, sample samples are stored and can be reanalyzed with new methods for ten years after collection. So the absence of a positive result today does not guarantee that the violation will not be detected later.
Typical mistakes and responsibility of the athlete
The World Anti-Doping Code is based on the principle of strict liability: an athlete is responsible for any prohibited substance found in his sample, regardless of intent. This has several practical implications for insulin.
The first common mistake is that an athlete with diabetes does not issue a TUE on time, thinking that "diabetes is obvious." Even with an undisputed diagnosis, the lack of permission at the time of testing creates a legal problem. The second is changing the insulin drug without updating the information in the documents, which can complicate the review.
The third mistake concerns healthy athletes who consider insulin "undetectable." As we have seen, analogs are detected by direct methods, and samples are stored for years. In addition to anti-doping sanctions, such an athlete risks his life due to severe hypoglycemia, especially during intense training.
Finally, it is worth remembering about the investigation without a positive sample. Possessing prohibited substances without medical justification, transferring them to others or attempting to use them are also anti-doping rule violations. Team personnel, doctors and trainers bear separate responsibility.
Editorial conclusions
Insulins and insulin mimetics are permanently banned by WADA under Section S4 "Hormonal and Metabolic Modulators". The ban applies both at competitions and outside them.
Athletes with diabetes may legally use insulin with a therapeutic use permit; the procedure is clearly described in the International TUE Standard and the WADA Guidelines for Physicians.
Synthetic analogues of insulin are detected by direct mass spectrometry methods, and sample samples can be reanalyzed for years. The idea that insulin is "undetectable" is a dangerous myth, as is the idea that it is safe.
We also recommend reading our materials "Why Insulin is Used in Sports: Expectations and Reality", "Contraindications to Insulin" and "Insulin and the Heart: Risks for the Cardiovascular System".
List of used literature
- World Anti-Doping Agency. Prohibited List. Montreal: WADA; Ñинна ÑедакÑÑÑ.
- World Anti-Doping Agency. International Standard for Therapeutic Use Exemptions (ISTUE). Montreal: WADA; Ñинна ÑедакÑÑÑ.
- World Anti-Doping Agency. TUE Physician Guidelines: Diabetes Mellitus. Montreal: WADA.
- World Anti-Doping Agency. World Anti-Doping Code 2021. Montreal: WADA; 2021.
- Thevis M, Thomas A, Schänzer W. Insulin. Handb Exp Pharmacol. 2010;(195):209â226.
- Sonksen P. Insulin, growth hormone and sport. J Endocrinol. 2001;170(1):13â25.
- Anderson LJ, Tamayose JM, Garcia JM. Use of growth hormone, IGF-I, and insulin for anabolic purpose: pharmacological basis, methods of detection, and adverse effects. Mol Cell Endocrinol. 2018;464:65â74.
