What are the findings on the carcinogenicity of Ozempic (semaglutide)?

From the Guidelines

Current evidence suggests that Ozempic (semaglutide) does not significantly increase cancer risk in humans, although long-term studies are still ongoing to fully evaluate carcinogenicity risks. Studies on Ozempic and carcinogenicity have shown mixed results, with preclinical animal studies finding thyroid C-cell tumors in rodents, but this effect appears to be rodent-specific and has not been observed in humans 1. The FDA requires a boxed warning about medullary thyroid carcinoma risk, but this is based on animal data rather than human evidence. Clinical trials of Ozempic have not demonstrated an increased cancer risk in humans, and the mechanism behind the rodent findings involves GLP-1 receptors on thyroid C-cells that, when continuously stimulated, can lead to tumor development in these species 1. Humans have fewer GLP-1 receptors on thyroid cells, which may explain the species difference.

Some key considerations for the use of Ozempic include:

• Patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 should avoid Ozempic 1
• Continued monitoring is recommended as the medication is relatively new to market
• Ozempic has demonstrated cardiovascular safety in a dedicated cardiovascular outcome trial 1
• The medication may cause gastrointestinal side effects, pancreatitis, and other potential safety concerns, and patients should be counseled on these risks 1

Overall, the current evidence suggests that Ozempic can be a safe and effective treatment option for patients with type 2 diabetes, although careful consideration of the potential risks and benefits is necessary.

From the FDA Drug Label

In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma exposures [see Nonclinical Toxicology (13. 1)]. It is unknown whether OZEMPIC causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans.

The FDA drug label indicates that ozempic (semaglutide) has been associated with an increased incidence of thyroid C-cell tumors in rodents, but it is unknown whether this risk applies to humans. There have been postmarketing reports of medullary thyroid carcinoma (MTC) in patients treated with another GLP-1 receptor agonist, liraglutide, but the data are insufficient to establish a causal relationship.

• Key points:
  • Increased incidence of thyroid C-cell tumors in rodents
  • Unknown risk in humans
  • Postmarketing reports of MTC with liraglutide
  • Insufficient data to establish causal relationship 2, 2, 2

From the Research

Ozempic and Carcinogenicity Studies

• There are no direct studies on Ozempic (semaglutide) and carcinogenicity in the provided evidence.
• However, studies have investigated the safety and efficacy of semaglutide in patients with type 2 diabetes, which may provide some insights into its potential effects on cancer risk 3, 4, 5.
• A meta-analysis of the SUSTAIN and PIONEER trials found that semaglutide had a good safety profile in general, but increased the risk of deep vein thrombosis and diarrhea 4.
• Another study found that semaglutide was associated with a beneficial effect on body weight and systolic blood pressure, but also increased the incidence of nausea, vomiting, and diarrhea 5.
• A study on the efficacy and safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in patients with type 2 diabetes found that semaglutide 2.0 mg was superior to 1.0 mg in reducing HbA1c, with additional bodyweight loss and a similar safety profile 3.
• There is no evidence to suggest that semaglutide increases the risk of cancer, but further studies are needed to fully assess its safety profile 4, 5.

Limitations of Current Studies

• The current studies on semaglutide have focused on its efficacy and safety in patients with type 2 diabetes, rather than its potential effects on cancer risk 3, 4, 5.
• More research is needed to fully understand the potential effects of semaglutide on cancer risk and to determine its safety profile in different patient populations 4, 5.
• The studies on semaglutide have been sponsored by Novo Nordisk, the manufacturer of the drug, which may introduce bias into the results 3.