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A Scandinavian cohort study suggested a popular class of diabetes drug did not put patients at an elevated risk for thyroid cancer, a longtime lingering concern with this drug class.

Compared with DPP-4 inhibitors, patients who were newly prescribed a GLP-1 receptor agonist did not have a significantly higher risk of developing thyroid cancer over an average 4-year follow-up (HR 0.93, 95% CI 0.66-1.31), Björn Pasternak, MD, PhD, of the Karolinska Institutet in Stockholm, and colleagues reported in .

Only 76 of the 145,410 patients who used a GLP-1 agent developed thyroid cancer (incidence rate 1.33 events per 10,000 person-years), while 184 of 291,667 of new DPP-4 users did (IR 1.46 events per 10,000 person-years).

"The safety data reported here may help inform decision making when treatment with GLP-1 receptor agonists are considered," Pasternak told MedPage Today.

"Concerns about thyroid cancer with GLP-1 receptor agonists have lingered ever since the preclinical development of these drugs, when experimental studies showed increased rates of a certain type of thyroid tumor in rodents," he explained. "Although the relevance of this to humans is not known, subsequent reports based on different sources of data in humans collectively point to the possibility that there might be an increased risk."

He added that prior studies haven't been conclusive because of data and methodology limitations, leading this potential drug safety concern to be surrounded by uncertainty.

Pasternak pointed out that his study supports the into the matter that concluded that available evidence did not support a causal link between GLP-1 agonists and thyroid cancer. This review included semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), and exenatide (Byetta, Bydureon).

While the FDA hasn't done its own investigation of this issue, the label of most approved GLP-1 receptor agonists carry a boxed warning about the risk for thyroid C-cell tumors and advise against use in patients with a personal or family history of medullary thyroid carcinoma or in those with multiple endocrine neoplasia syndrome type 2.

"Given that thyroid cancer is mentioned in the product label as a potential adverse event, spontaneous reporting may have been driven by physician and public awareness," the researchers noted.

Patients from Denmark, Norway, and Sweden were represented in the analysis. All included patients were between the ages of 18 to 84 newly initiating a GLP-1 receptor agonist or DPP-4 inhibitor. Prior thyroid cancer and genetic syndromes linked with thyroid cancer were two of the exclusion criteria.

The most commonly prescribed GLP-1 agent was liraglutide (57.3%), followed by semaglutide (32.9%), dulaglutide (4.9%), exenatide (4.1%), and the now-discontinued lixisenatide (0.9%).

Researchers found GLP-1s remained clear of a thyroid-cancer link when they looked more closely at different subtypes of thyroid cancer:

• Papillary: HR 0.92 (95% CI 0.61-1.39)
• Follicular: HR 0.99 (95% CI 0.47-2.08)
• Medullary: HR 1.19 (95% CI 0.37-3.86)
• Other: HR 1.51 (95% CI 0.44-5.20)

However, they noted there was only a small number of these thyroid cancer subtypes and the estimates for subtypes other than papillary were "imprecise." Because of the small sample sizes, they also couldn't assess subgroups of patients, like those with prior cancers or those with conditions putting them at elevated thyroid cancer risk, like multiple endocrine neoplasia syndrome type 2.

"We cannot rule out that the risk of certain subtypes of thyroid cancer is increased in smaller patient groups that we could not study here," noted co-author Peter Ueda, MD, PhD, also of the Karolinska Institutet, in a statement.

The researchers also compared GLP-1 users' thyroid cancer risk against users of another new and popular class of diabetes agents -- SGLT2 inhibitors, such as dapagliflozin (Farxiga), canagliflozin (Invokana), empagliflozin (Jardiance), or ertugliflozin (Steglatro). When compared with the SGLT2 class, GLP-1 users still didn't have an elevated thyroid cancer risk (HR 1.16, 95% CI 0.65-2.05).

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