GLP-1RA users face no elevated risk of pancreatic cancer

Among individuals with type 2 diabetes, the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) does not contribute to increased pancreatic cancer risk, according to a study.

In a historical cohort of adults with type 2 diabetes, GLP-1RA users were not at higher risk of pancreatic cancer risk in the 5–7 years following treatment initiation as compared with basal insulin users (adjusted hazard ratio [HR], 0.50, 95 percent confidence interval [CI], 0.15–1.71). [JAMA Netw Open  2024;7:e2350408]

The finding held true in both “new-user” (initiating either GLP-1RA or basal insulin) and “prevalent new-user” (switching from basal insulin to GLP-1RA) analyses. The respective adjusted HRs for pancreatic cancer among GLP-1RA users vs basal insulin users were 0.52 (95% CI, 0.19-1.41) and 0.75 (95% CI, 0.37-1.53) over the 5th to 7th year of follow-up.

Concerns regarding the potential pancreatic risks of GLP-1RAs were spurred by previous research suggesting an association with pancreatitis and pancreatic cancer. This prompted a Food and Drug Administration (FDA) warning on pancreatic safety and recommendation that patients and healthcare professionals report adverse events involving incretin mimetics to the FDA MedWatch program. [Gastroenterology 2011;141:150-156; JAMA Intern Med 2013;173:534-539; https://www.fda.gov/Drugs/DrugSafety/ucm343187.htm]

The evidence regarding GLP-1RA’s safety for the pancreas has been mixed. For example, multiple meta-analyses showed that GLP-1RA was associated with neither acute pancreatitis nor with pancreatic cancer. A pharmacovigilance study of the FDA FAERS data, on the other hand, reported an almost 10 times greater risk of pancreatic cancer with GLP-1RA treatment than with other glucose-lowering medications. [Diabetes Obes Metab 2017;19:906-908; Lancet Diabetes Endocrinol 2018;6:105-113; Lancet Diabetes Endocrinol 2019;7:776-785; Front Pharmacol 2022;13:925377]

Meanwhile, the present study used data from the Clalit Healthcare Services and included 543,595 adults (mean age 59.9 years, 51 percent women) with incident diabetes. Clalit database, according to the investigators, is of high quality and has been the source of many research reports, assuring the validity of the present study’s findings. [Am J Epidemiol 2019;188:1794-1800; Cancer Epidemiol 2018;57:104-109; J Clin Endocrinol Metab 2013;98:2160-2167; N Engl J Med 2021;384:1412-1423]

“Our analysis was adjusted for potentially important factors associated with risk for pancreatic cancer, such as smoking, obesity, and history of pancreatitis before GLP-1RA or basal insulin treatment,” they added.

All the participants in the study were followed up over a 9-year period (mean 6.1 years), with 3,290,439 person-years with diabetes accrued. During this period, 1,665 participants received pancreatic cancer diagnoses. In total, 33,377 patients (6.1 percent) used GLP-1RA and 106,849 (19.7 percent) used basal insulin. Most of the participants had overweight (37 percent with body mass index [BMI] 25–29.9 kg/m²) or obesity (42 percent with BMI ≥30 kg/m²), and were of low socio-economic status (59.0 percent). About one-third of the cohort had a history of smoking (35.8 percent).

While the study provides evidence on the safety profile of GLP-1RAs in terms of pancreatic cancer risk for up to 7 years, ongoing monitoring beyond this period is still warranted, the investigators said.