Several years after initiating treatment, GLP-1 receptor agonist users didn’t have a pancreatic cancer safety signal, a historical cohort study reported.
Compared with basal insulin users, those on a GLP-1 receptor agonist didn’t have a significantly different risk for developing pancreatic cancer in the 5 to 7 years that followed (HR 0.50, 95% CI 0.15-1.71), found Rachel Dankner, MD, MPH, of Sheba Medical Center in Ramat, Israel, and colleagues.
This model was adjusted for variables that included age, sex, ethnic background, sociodemographic status, baseline body mass index (BMI), smoking history, history of pancreatitis, other glucose-lowering medications treatment history, and length of diabetes, they pointed out in JAMA Network Open.
Findings were similar when Dankner’s group separated out new users of basal insulin and compared them with new initiators of GLP-1 receptor agonists (HR 0.52, 95%CI 0.19-1.41). Likewise, there was still no pancreatic safety signal when the model compared basal insulin users with GLP-1 users who were previously on basal insulin (HR 0.75, 95% CI 0.37-1.53).
“I was relieved to find out that no association was found between GLP-1 receptor agonist medications and pancreatic cancer incidence,” Dankner told MedPage Today. “This finding was consistent, no matter which analytical approach we took, which made me more certain that these findings are not spurious, and we accounted for important confounding factors such as history of pancreatitis, smoking habits, and BMI.”
“I hope this study will reduce doctors’ concerns when prescribing GLP-1 receptor agonist glucose-lowering medications to their patients,” she added. “It is important for the treating physician to know they are not causing harm when prescribing these medications.”
A few years after the first GLP-1s hit the market, the FDA released a warning after a 2013 case-control study linked this medication class with pancreatitis and pancreatic duct metaplasia. Since then, there has been a mixed bag of research surrounding pancreatic safety associated with this popular medication class. Pancreatitis is listed as a potential warning on GLP-1 labels, but risk for pancreatic cancer is not.
For this population-based cohort study, the researchers looked at Israeli adult patients between the ages of 21 to 89 (average age 60) with type 2 diabetes insured by Clalit Healthcare Services. Follow-up of these patients started in 2009 when the first GLP-1 receptor agonist became available in Israel.
Of the 543,595 patients in the cohort, 37% had overweight, 42% had obesity, 35.8% had a history of smoking, and 59% were of low socioeconomic status. Only 6.1% of the cohort had ever used a GLP-1 receptor agonist. These patients tended to be younger and were more likely to have obesity than basal insulin users.
During follow-up, 3.3% of GLP-1 users and 3.5% of basal insulin users experienced pancreatitis. Overall, the crude rate of pancreatic cancer cases was similar between GLP-1 users and nonusers, though basal insulin users had a slightly higher rate compared with non-insulin users. The researchers suggested this was likely due to basal insulin users being older and having a longer duration of diabetes.
While this study only looked at the association between GLP-1 receptor agonists and pancreatic cancer among a population with type 2 diabetes, Dankner said she expects the findings to also apply to a population with obesity — an indication that has shot this class of medication to popularity in recent years.
“The lack of an association in our study was independent of patient’s BMI,” she said. “It leads me to assume that GLP-1 receptor agonists may be safe in respect to pancreatic cancer risk, not only when given as a glucose lowering medication to diabetic patients, but also as a weight reduction medication to obese patients, who are often times the same patient population.”
One limitation of the study was its observational design, though Dankner said her group’s “analytical approach practically emulated a randomized clinical trial.” She added that they also only looked at pancreatic cancer risk through 7 years of follow-up and that “pancreatic cancer’s latency period may be longer than that.”
Dankner and co-authors reported no disclosures.
JAMA Network Open
Source Reference: Dankner R, et al “Glucagon-like peptide-1 receptor agonists and pancreatic cancer risk in patients with type 2 diabetes” JAMA Netw Open 2023; DOI: 10.1001/jamanetworkopen.2023.50408.