TOPLINE:

In patients with type 2 diabetes (T2D), the use of GLP-1 receptor agonists (RAs) is not associated with an increased risk for most serious gastrointestinal (GI) or hepatobiliary outcomes over 5 years, except for gastroparesis and intussusception. GLP-1 RA use is also associated with lower risks for several GI cancers compared with other oral antidiabetic medications.

METHODOLOGY:

• GLP-1 RAs can cause mild GI symptoms (eg, nausea and vomiting) and have been linked to severe toxicities, yet data on pancreatitis and cancer remain conflicting. Most prior studies were small or short-term or focused on select agents.
• In this retrospective cohort study, researchers analyzed electronic health records of adults with T2D treated across the United States between January 2010 and March 2020.
• Patients receiving GLP-1 RAs (exenatide, lixisenatide, semaglutide, dulaglutide, or liraglutide) were propensity score-matched to patients treated with other oral antidiabetic agents (eg, empagliflozin, metformin, and sitagliptin).
• Primary outcomes included GI and hepatobiliary adverse events (eg, cholecystitis, pancreatitis, gastroparesis, and bowel obstruction) and GI cancers, which were assessed over 5 years of follow-up.

TAKEAWAY:

• Researchers included 230,415 GLP-1 RA users (mean age, 57.2 years; 54.3% women) and an equal number of matched patients taking other oral antidiabetic medications (mean age, 56.9 years; 54.3% women).
• GLP-1 RA use was associated with higher risks for gastroparesis (hazard ratio [HR], 1.591; P < .001) and intussusception (HR, 1.383; P = .025) than the use of other oral antidiabetic medications.
• GLP-1 RA users had approximately 15%-26% lower risks for cholangitis, bowel obstruction, ileus, volvulus, chronic pancreatitis, and endoscopic retrograde cholangiopancreatography than those using other oral antidiabetic medications (P < .05 for all), with no significant differences for acute pancreatitis, cholecystitis, or cholecystectomy.
• Risks for pancreatic, gastric, esophageal, and colorectal cancers were approximately 10%-26% lower among GLP-1 RA users (P < .05 for all), with no significant differences for biliary cancer or hepatocellular carcinoma.

IN PRACTICE:

“In patients with preexisting GI conditions — such as gastroparesis and intussusception — clinicians may consider preferring traditional oral anti-[diabetes mellitus] medications. And for patients at risk for cholangitis, bowel obstruction, ileus, volvulus, chronic pancreatitis, common GI malignancies, GLP-1 RA may still be a safe choice for its safety profile observed in this study,” the authors wrote.

SOURCE:

This study was led by Chengu Niu, MD, Rochester General Hospital in Rochester, New York. It was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The results showed associations not causation. The 5-year follow-up may not have captured long-term cancer risks. Socioeconomic status and access to healthcare may have influenced treatment choices. Treatment duration, adherence, and medication switching were not assessed.

DISCLOSURES:

This study received no specific funding. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.