Current and emerging medications for the management of obesity in adults

To the Editor: We congratulate Walmsley and Sumithran1 for their excellent review on medications for the management of obesity in adults. We also wish to highlight a safety signal for thyroid cancer with glucagon‐like peptide 1 (GLP‐1) receptor agonists, which is a relevant issue to prescribers given the widespread use of these agents for obesity.

Preclinical studies in rodents demonstrated that all GLP‐1 receptor agonists caused thyroid C cell tumours. However, the relevance to humans was unclear, as these did not occur in toxicology studies in monkeys.2 Given the rarity of medullary thyroid cancer (MTC), which has an estimated incidence of 0.2 cases per 100000 patient‐years,2 there were insufficient events to detect a signal in a meta‐analysis of clinical trials investigating the GLP‐1 receptor agonist semaglutide.3 Pharmacovigilance activities on the incidence of MTC are ongoing.2

The United States Food and Drug Administration added a boxed warning about this risk for semaglutide, dulaglutide and liraglutide. It recommends against their use in patients with personal or family history of MTC, including multiple endocrine neoplasia syndrome type 2 (MEN2). By contrast, the Therapeutic Goods Administration (TGA) does not have this contraindication in the product information.

A recent French study has raised concerns about this safety signal.4 This population‐based case‐controlled study assessed the association between GLP‐1 receptor agonist use and thyroid cancer in individuals with diabetes. They found that the use of GLP‐1 receptor agonists was associated with an increased risk of both medullary and papillary thyroid cancer after adjustment for covariates.

As stated in an accompanying editorial,5 it is possible that GLP‐1 receptor agonists cause a moderate increase in the risk of thyroid cancer, or this could reflect detection bias. Regardless, a potential increase in risk needs to be weighed against the larger reduction in absolute risk of cardiovascular events with GLP‐1 receptor agonists for people with diabetes.

Pending further studies on this issue, we recommend prescribers consider the risks and benefits of GLP‐1 receptor agonists for obesity. Cardiovascular outcomes trials in populations without diabetes are ongoing. In our view, it would be prudent to avoid GLP‐1 receptor agonists in patients with a personal or family history of MTC or MEN2. The product information should be updated to reflect this risk. Any thyroid cancer suspected of being related to GLP‐1 receptor agonists should be reported to the TGA.