Hot GLP-1 drugs have been warned by EMA for safety risks. What did they say and what is the basis? Can we still lose weight lying down?
This week, a report from Reuters has cast a shadow over GLP-1 drugs, suggesting that the weight-loss miracle drug may lead to thyroid cancer, dampening the hot GLP-1 market with a cold shower from the EMA (European Medicines Agency).
Beauty lovers who have been hoping to "lose weight while lying down" with weight-loss drugs are now worried.
Why did EMA issue this article and what is the basis?
This article originated from a drug safety risk advisory issued by the EMA in May. The EMA has raised a safety signal for thyroid cancer for products targeting GLP-1, which is used for diabetes and obesity. This is one way of monitoring potential adverse events of approved drugs.
It is worth noting that this risk is not targeted at Novo Nordisk's semaglutide alone, but rather a large class of GLP-1 drugs, including Dulaglutide, Exenatide, Insulin Degludec+Liraglutide, Liraglutide, Lixisenatide, Insulin Glargine+Lixisenatide, and Semaglutide. Novo Nordisk, Lilly, AstraZeneca, and Sanofi are required to provide additional risk information by July 26.
Through AI research, a study published in Diabetes Care this year, titled "GLP-1 Receptor Agonists and the Risk of Thyroid Cancer," is related to the EMA's theme.
The researchers of this study conducted a retrospective case-control analysis of relevant cases using the French National Health Insurance System (SNDS) database, including type 2 diabetes patients who received second-line anti-diabetic drug treatment between 2006 and 2018. All cases of thyroid cancer were determined through hospital discharge diagnosis and medical procedures between 2014 and 2018. The use of GLP-1 receptor agonists (GLP-1 RA) was measured within the first 6 years and considered as cumulative use based on defined daily doses (≤1 year, 1-3 years, >3 years).
A total of 2562 cases of thyroid cancer and 45184 control cases were identified. The use of GLP-1 RA drugs for 1-3 years was associated with an increased risk of all thyroid cancer (adjusted hazard ratio [HR] 1.58, 95% CI 1.27-1.95) and medullary thyroid cancer (adjusted HR 1.78, 95% CI 1.04-3.05), with a greater risk for women than men.
Therefore, the study concluded that the use of GLP-1 drugs, especially after 1-3 years of treatment, increases the risk of all thyroid cancer and medullary thyroid cancer.
However, this is not the first time that the EMA has requested information on GLP-1 drugs. The risk of thyroid cancer, in particular, has even been observed in animal experiments with GLP-1.
The popular drug semaglutide has a black box warning for thyroid cancer in its drug label
The popular weight loss drug semaglutide has a black box warning for the risk of thyroid cancer in its drug label.
In short, although thyroid cancer risk has been found in rodents, the risk is low in primates because C cells are not expressed. In rodents, semaglutide can cause dose-dependent and treatment-time-dependent thyroid C cell tumors, which are clinically relevant. It is currently unclear whether WEGOVY and RYBELSUS (semaglutide brand names) will cause thyroid C cell tumors in humans, including medullary thyroid cancer (MTC), because the human relevance of semaglutide-induced thyroid C cell tumors in rodents has not been established.
WEGOVY and RYBELSUS are contraindicated in patients with a personal or family history of MTC and in patients with multiple endocrine neoplasia type 2 (MEN 2). Patients should be informed that the use of RYBELSUS may increase the risk of MTC and be advised of the symptoms of thyroid tumors (such as neck lumps, difficulty swallowing, difficulty breathing, and persistent hoarseness). The value of regular monitoring of serum calcitonin or the use of thyroid ultrasound for early detection of MTC in patients treated with WEGOVY and RYBELSUS is uncertain.
Doctors will prompt thyroid examination before use, GLP-1 market will not be affected
Looking back at the EMA's risk warning, it actually confirms the potential strong market demand for GLP-1 from the side. Especially because of the strong demand for weight loss, the population who come into contact with GLP-1 drugs has increased significantly, and potential thyroid risk patients are also increasing rapidly.
From the experience of domestic users, even if they skip the doctor's choice and use online shopping, doctors usually recommend that patients go to the hospital for thyroid-related examinations first. If there are relevant risks, doctors will not recommend use.
On the other hand, semaglutide has now covered more than 15 different diseases in clinical trials. This means that with the growth of GLP-1 indications approved, there is a trend of long-term use, especially for people with relatively low BMI index in weight loss indications, the potential impact of side effects will be far greater than its benefits.
After all, curing diseases - high-quality survival - high-quality life are different levels of demand, and the tolerance for side effects decreases in turn. This will inevitably put higher demands on data research on the safety risks of use.
In addition, for large companies, GLP-1 may be beneficial to increasing potential lifespan, but this type of clinical trial itself requires a lot of funding support. For such clinical trials, if successful, it will mean a very considerable long-term moat for the company, but at the same time, it means that any safety issues are very important, after all, any other possible side effects will lead to endpoint failure.
Therefore, everyone should not be scared by this EMA drug safety information update. But does this also mean that the healthy weight loss method of controlling the mouth and moving the legs should not be abandoned by everyone?
