Could GLP1-based medications reduce the risk of peptic ulcer disease?

GLP-1 medications were first developed to treat type 2 diabetes, and subsequently for weight management. In more recent years, a host of other benefits have emerged for some of these medications, including cardiovascular protection, diabetes prevention, treatment of MASH (‘fatty liver’), heart failure with preserved ejection fraction (HFpEF), sleep apnea, and knee osteoarthritis in people with obesity (check out our 2025 Obesity Canada Pharmacotherapy Guidelines for details on these – disclosure, I am the lead author).

I was fascinated by a recent hypothesis-generating study which suggested yet another potential benefit to GLP1 medications, that being a lower risk for peptic ulcer disease (stomach ulcers) .

This retrospective cohort study analyzed an American NIH database of over 66,000 adults with type 2 diabetes, looking at the odds of being diagnosed with peptic ulcer disease (PUD) after being prescribed GLP1 medications compared to people not prescribed GLP1s, adjusting for use of other medications such as insulin, anti inflammatory medications (NSAIDs), steroids, and proton pump inhibitors. They found that people prescribed GLP1s had a 44% lower risk of being diagnosed with PUD compared to people not prescribed GLP1s. Over a median follow-up of almost 5 years, people prescribed a switch to GLP1 as a second-line treatment for their type 2 diabetes had a 56% lower risk of PUD compared to those prescribed a switch to insulin.

As this was a retrospective cohort study and not a proper clinical trial, we have to take the results with a big grain of salt. People prescribed GLP1 were younger, with higher BMI, better baseline diabetes control, and a lower burden of other medical conditions than those prescribed insulin. Though the authors did adjust for these potential confounders in their analysis, they also correctly note that there could be other unmeasured differences between groups (eg dietary habits, adherence to medication) that could have influenced the results. The study did not account for H pylori infection as data were not available for this, which is a major risk factor for PUD.

How could GLP1 medications reduce peptic ulcer risk? GLP1 medications have been shown to decrease systemic inflammation and oxidative stress. GLP1s may increase local blood flow to the stomach lining, promoting tissue repair and making the lining of the stomach more resilient against ulcer development. This may seem counterintuitive as GLP1s also slow stomach emptying, thus prolonging exposure of the stomach lining to stomach acid, but perhaps the other mechanisms may outweigh this. GLP1s may also change the gut bacteria in favor of more ulcer-protective bacteria.

BOTTOM LINE: This retrospective observational study suggests that GLP1 use may be associated with a lower risk of developing peptic ulcer disease. Proper prospective randomized clinical trials are needed to explore this fascinating possibility.

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