The retrospective cohort analysis used data from the TriNetX Dataset and examined the outcomes of over 2.3 million adults diagnosed with T2DM between January 2019 and December 2022. All participants had an estimated glomerular filtration rate of at least 60 mL/min/1.73 m², ensuring the inclusion of patients with preserved kidney function.
To assess the GI outcomes, this research applied a new-user, active-comparator design. The patients prescribed dipeptidyl peptidase-4 inhibitors (DPP4i) were designated as the control group. After propensity score matching based on baseline characteristics such as age, sex, and comorbidities, 2 balanced cohorts were created, each consisting of 127,216 patients, where one group on GLP1-RA therapy and the other on DPP4i.
The average patient age was approximately 60 years, with 55% male and 63% identifying as White. Over a four-year follow-up, Cox proportional hazards regression models revealed notable GI benefits among GLP1-RA users.
Specifically, GLP1-RA treatment lowered the risk of acute pancreatitis (HR: 0.90, CI: 0.83–0.97), liver failure (HR: 0.81, CI: 0.75–0.88), peritonitis (HR: 0.85, CI: 0.76–0.94), peptic ulcer (HR: 0.89, CI: 0.84–0.94), and GI bleeding (HR: 0.95, CI: 0.92–0.98). These reductions, while varied in magnitude, consistently favored GLP1-RA over DPP4i across different statistical models, which strengthened the confidence in these findings.
The results highlight that beyond their well-documented ability to lower cardiovascular risk and slow kidney disease progression, GLP1-RAs may offer a new dimension of protection for patients with T2DM by reducing serious GI complications. This could prove particularly valuable in guiding personalized treatment choices, especially for patients at heightened risk of gastrointestinal disease. GLP1-RA therapy appears to deliver meaningful GI protection when compared to DPP4 inhibitors.
Overall, these findings suggest that GI outcomes should be considered along with cardiovascular and renal factors when tailoring treatment strategies for type 2 diabetes. With T2DM patients often facing multiple health risks simultaneously, this study reinforces GLP1-RA’s growing reputation as a comprehensive therapeutic option, potentially reshaping how clinicians weigh treatment choices in routine practice.
Source:
Hsu, J.-H., Bai, H.-F., Chen, M.-T., Fang, Y.-W., Wang, J.-T., Liu, C.-Y., & Tsai, M.-H. (2025). Glucagon-like peptide-1 receptor agonists lead to gastrointestinal benefits in patients with type 2 diabetes: A real-world study. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 31, e946935. https://doi.org/10.12659/MSM.946935
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