From the Guidelines
There are no confirmed case studies definitively linking GLP-1 medications to cancer development, and patients taking these medications should continue their prescribed regimen and discuss any concerns with their healthcare provider rather than discontinuing treatment based on unconfirmed cancer risks. While some early concerns were raised about potential associations between GLP-1 medications (such as semaglutide/Ozempic/Wegovy, liraglutide/Victoza/Saxenda, tirzepatide/Mounjaro/Zepbound, and dulaglutide/Trulicity) and specific cancers like medullary thyroid cancer or pancreatic cancer, large clinical trials and post-marketing surveillance have not established a causal relationship 1. The initial concerns stemmed from animal studies showing thyroid C-cell tumors in rodents, but human physiology differs significantly from these models.
Some key points to consider when evaluating the safety of GLP-1 medications include:
- The FDA includes warnings about medullary thyroid carcinoma in the prescribing information for these medications, and they are contraindicated in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 1.
- Long-term safety studies are ongoing, as these medications have only been widely used for a relatively short time.
- GLP-1 receptor agonists have high glucose-lowering efficacy, but with variation within the drug class, and evidence suggests that the effect may be greatest for semaglutide once weekly, followed by dulaglutide and liraglutide 1.
- All GLP-1 receptor agonists have minimal risk for hypoglycemia, but may increase the hypoglycemic potential of insulin and sulfonylureas when combined with those medications 1.
In terms of specific cancer risks, the current evidence does not support a causal relationship between GLP-1 medications and cancer development. However, it is essential to continue monitoring the safety of these medications and to discuss any concerns with healthcare providers. The benefits of GLP-1 medications in improving glycemic control and reducing cardiovascular risk shouldn't be overlooked, and patients should not discontinue treatment based on unconfirmed cancer risks.
From the FDA Drug Label
In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure [see Nonclinical Toxicology (13. 1)]. Glucagon-like peptide-1 (GLP-1) receptor agonists have induced thyroid C-cell adenomas and carcinomas in mice and rats at clinically relevant exposures. One case of MTC was reported in a patient treated with TRULICITY in a clinical trial. An additional case of C-cell hyperplasia with elevated calcitonin levels following treatment was reported in the cardiovascular outcomes trial (REWIND) 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. Neoplasms: Medullary thyroid carcinoma
The case studies of cancers associated with Glucagon-like peptide-1 (GLP-1) receptor agonist medications include:
- Medullary thyroid carcinoma (MTC): One case of MTC was reported in a patient treated with dulaglutide in a clinical trial, and cases of MTC have been reported in patients treated with liraglutide in the postmarketing period.
- Thyroid C-cell tumors: Dulaglutide has been shown to cause an increase in the incidence of thyroid C-cell tumors in male and female rats.
- C-cell hyperplasia: An additional case of C-cell hyperplasia with elevated calcitonin levels following treatment was reported in the cardiovascular outcomes trial (REWIND). 2 3 3
From the Research
Cancers Associated with GLP-1 Receptor Agonist Medications
- Pancreatic cancer: Current studies do not prove an increased risk of pancreatic cancer, but more trials are needed to address concerns about safety 4
- Thyroid cancer: Research has confirmed that GLP-1 RAs do not increase the risk of thyroid cancer, but more trials are needed to address concerns about safety 4
- Colorectal cancer: It is assumed that GLP-1 receptor agonists may increase the risk for colorectal cancer due to their effect on the Wnt/β-catenin pathway, which is associated with tumorigenesis in the colon 5
- Neoplasms: The risk of neoplasms is generally low across the GLP-1 RAs investigated 6
Case Studies of Cancers
- A narrative review comparing the safety and tolerability of three QW GLP-1 RAs (dulaglutide, exenatide extended-release, and semaglutide) found that the risk of pancreatitis, neoplasms, and gallbladder events was generally low across the GLP-1 RAs investigated 6
- The SUSTAIN 6 trial reported significantly more diabetic retinopathy complications (DRC) events in patients treated with QW semaglutide (3.0%) compared with placebo (1.8%) 6
GLP-1 Receptor Agonist Medications and Cancer Risk
- GLP-1 RAs have been associated with an increased risk of certain cancers, but the evidence is limited and more research is needed to fully understand the relationship between GLP-1 RAs and cancer risk 4, 5, 6
- The safety profiles of different GLP-1 RAs vary, and each medication should be considered individually when assessing cancer risk 6