Counterfeit semaglutide: the danger of illegal injections

Two hospital admissions caused by counterfeit disposable pens

The case studies described by doctors at the Albert Schweitzer Hospital and Deventer Hospital in the NTvG provide a good insight into what can go wrong.

A 55-year-old man with no relevant medical history woke up during the night feeling nauseous, sweaty and unwell. He collapsed on his way to the toilet and was found in a comatose state by his wife. The ambulance crew recorded a blood glucose level of 1.7 mmol/l, which is well below normal. On arrival at A&E, it was found that he also had a body temperature of 32.2 °C and a low potassium level. He had been using semaglutide for six months to treat obesity, initially on prescription from a treatment clinic, and later via a cheaper online supplier. At one point, that supplier sent him a different type of pen, with an English-language label and a patient information leaflet stating that the dosage could be increased progressively.

A 47-year-old woman with no relevant medical history was also found comatose during the night, this time by her son. Her blood glucose level was even lower, at 1.1 mmol/l, with a temperature of 34.0 °C and an obstructed airway. She had been using semaglutide for a month to lose weight, obtained through an acquaintance because her GP saw no medical indication to prescribe it. She was in possession of two unauthorised pens, one labelled in German and one in Bulgarian, and had injected an unknown quantity from both the evening before her admission.

In both patients, laboratory tests using a specialised technique (LC-MS/MS) ultimately confirmed insulin intoxication. In the man, the synthetic insulin glulisine was detected. In the woman’s case, the pen with Bulgarian labelling contained a mixture of insulin glulisine, insulin aspart and human insulin, whilst the pen with German labelling was found to contain semaglutide. Both patients recovered following treatment, although the woman reported still experiencing concentration problems a month later.

Why is this so dangerous? The science behind the risk

To understand why this result was so unexpected, it helps to know the difference between semaglutide and insulin.

Semaglutide belongs to the class of GLP-1 receptor agonists, medicines derived from the body’s own hormone, GLP-1. This hormone stimulates the production of insulin in the pancreas, but only when blood sugar levels are already elevated. As soon as blood sugar levels fall, this additional stimulation ceases automatically. In addition, GLP-1 reduces feelings of hunger and slows down gastric emptying, which contributes to a feeling of fullness.

Insulin and sulphonylureas work in fundamentally different ways. They lower blood sugar levels regardless of how much glucose is present in the blood. If the dose is too high, blood sugar levels continue to fall, even to dangerously low levels, resulting in severe hypoglycaemia. This explains why insulin intoxication can lead to coma, hypothermia and impaired potassium balance, whereas semaglutide does not, on its own, cause these effects.

Clinical trials of semaglutide as monotherapy therefore show no increased risk of severe hypoglycaemia. To date, such episodes of hypoglycaemia have only been reported in people with type 2 diabetes mellitus, and particularly when semaglutide is used in combination with insulin. In a person without diabetes who develops severe hypoglycaemia following an injection purchased as “semaglutide”, adulteration with insulin is therefore the most logical explanation, rather than a reaction to the drug itself.

How do counterfeit medicines end up in people’s hands?

The number of people using GLP-1 receptor agonists in the Netherlands has risen sharply in recent years, partly due to the increased focus on these medicines for weight management. However, semaglutide is only authorised and reimbursed in the Netherlands for type 2 diabetes mellitus, subject to certain conditions. For weight loss without that indication, the medicine is not readily available through the standard healthcare system.

This combination – limited legal availability coupled with high demand – makes the market attractive to illegal sellers. They offer what they claim to be semaglutide without a prescription, without a medical assessment and often at a lower price than at an authorised treatment clinic.

Standard Dutch pharmacies check medicines in accordance with the European “Falsified Medicines Directive”. Each pack is given a unique code by the manufacturer and is sealed, and a pharmacist is obliged to check these two features before dispensing a medicine. Anyone who buys medication outside this system, such as via a website or a private seller, misses out on this check entirely. There is then no guarantee whatsoever that the contents of the pack match the label.