Weight Loss Drugs Linked to Lower Risk of Peptic Ulcer Disease in Adults with Diabetes

GLP1 Receptor Agonists were Associated with Fewer Ulcer Diagnoses in Large U.S. Study

Boston, MA — Medications widely prescribed for type 2 diabetes and weight management may offer an unexpected benefit for the gut. A large nationwide study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) found that people with type 2 diabetes who used GLP1 drugs were significantly less likely to develop peptic ulcer disease than those who did not use these medications.

The findings, published in Clinical Gastroenterology and Hepatology, draw on electronic health records (EHR) from more than 66,000 adults enrolled in the National Institutes of Health’s All of Us Research Program, one of the most diverse biomedical datasets in the United States.

“Peptic ulcer disease remains a significant cause of illness and hospitalization, particularly among people with type 2 diabetes, yet largescale clinical studies examining how newer diabetes medications affect ulcer risk have been lacking,” said Trisha Pasricha, MD, MPH, a gastroenterologist at BIDMC. “Our study was designed to address that gap and to better understand whether GLP1 receptor agonists are associated with meaningful differences in ulcer risk in this population.”

Peptic ulcers—painful open sores that form in the lining of the stomach or upper intestine—can cause persistent abdominal pain and nausea. Worldwide, an estimated four million people each year experience ulcer-related complications, including gastrointestinal bleeding and perforation. People with type 2 diabetes face a higher risk of peptic ulcer disease, a vulnerability thought to reflect chronic inflammation, metabolic stress, and frequent exposure to ulcer-promoting medications such as nonsteroidal anti-inflammatory drugs (NSAIDs).

Given this heightened vulnerability, Pasricha and colleagues examined whether GLP1 medications—first approved for diabetes care two decades ago and now much more widely prescribed—were associated with differences in peptic ulcer risk.

Overall, use of GLP1 drugs was linked with 44 percent lower odds of receiving a peptic ulcer diagnosis; that is, across the full population of people with diabetes who participated in the study, those using GLP1s were less likely to be diagnosed with peptic ulcer disease than those who were not, even after accounting for age, sex, body mass index, medication use, and other clinical factors.

In a focused analysis, Pasricha and colleagues examined participants who had stopped metformin, the standard first line treatment for type 2 diabetes, and then began either a GLP1 drug or insulin. In this head-to-head comparison, patients who switched to a GLP1 medication had a 56 percent lower risk of developing peptic ulcer disease than those who switched to insulin.

“Although these medications are not prescribed with ulcer prevention in mind, there is growing evidence that GLP1 receptor agonists may have broader biological effects, including anti-inflammatory properties and roles in gastrointestinal mucosal protection,” said senior author Pasricha, who is also an assistant professor of medicine at Harvard Medical School. “Those effects may help explain why we observed different ulcer risks compared with insulin.”

Importantly, the investigators observed that medications well known to increase ulcer risk—such as NSAIDs, steroid drugs, and blood thinners—were associated with higher risk as expected, lending credibility to the study’s methods. Together, these findings highlighted the use of GLP1s’ link with lower ulcer risk.

While GLP1 receptor agonists are best known for lowering blood sugar, driving weight loss, and reducing cardiovascular risk, an ever-growing body of research suggests these drugs also quiet inflammation and strengthen tissue repair in the gastrointestinal tract. More research will be needed to determine whether these effects actually help the stomach and small intestine better withstand injury—particularly in people with diabetes, who may already have impaired defenses.

Co-authors included Philippa Seika, Jocelyn Chang, Su Min Hong, Sarah Ballou, Vikram Rangan, Chethan Ramprasad, Johanna Iturrino, Judy Nee, and Subhash Kulkarni of BIDMC; Christian Denecke of Charité Universitätsmedizin; and, Anthony Lembo of Cleveland Clinic. 

This work was funded by the American Gastroenterological Research Foundation’s Research Scholar Award (AGA2022-13-03, Trisha Pasricha); the National Institute on Aging (grants R01AG66768 and R21AG0721070); the Diacomp Foundation (Pilot award Augusta University); a Pilot grant from the Harvard Digestive Disease Core to Subhash Kulkarni; and the Walter Benjamin Fellowship (528835020) from the Deutsche Forschungsgemeinschaft to Philippa Seika. The authors disclose no conflicts of interest.