Introduction and Objective: To assess if glucagon-like peptide-1 receptor agonist (GLP-1 RA) compared with sodium-glucose cotransporter 2 inhibitors (SGLT-2i), is associated with an increased risk of motility-related gastrointestinal (GI) adverse events.Methods: From two US commercial healthcare databases, we used 1-1 propensity score matching on >150 potential confounders to identify a cohort of adults with type 2 diabetes who initiated GLP-1 RA or SGLT-2i between Oct/2016-Aug/2024. The primary outcome was a composite of severe constipation, gastroparesis, and bowel obstruction. We calculated incidence rates and the hazard ratio (HR) with 95% confidence interval (CI) for the primary composite outcome.Results: Among 313,342 matched pairs of GLP-1 RA and SGLT-2i initiators (mean age 60 years; 45% female), followed on treatment for a median of 6.5 months, incidence rates of the composite outcome were 10.2 among GLP-1 RA versus 7.5 among SGLT-2i initiators per 100 person-years. The rate was significantly higher among GLP-1 RA versus SGLT-2i initiators (HR 1.37, 95% CI 1.30 to 1.45) for the composite event and for each of its individual components.Conclusion: We observed an increased risk of motility-related GI events associated with GLP-1 RA compared to SGLT-2i. These findings inform the risk benefit assessment by clinicians before initiating these treatments.
W. Alkabbani: None. S. Crisafulli: None. J.M. Paik: None. A. Tavakkoli: Consultant; Vertex Pharmaceuticals Incorporated, AltrixBio. K. Bykov: None. R. Glynn: Research Support; Amarin Corporation, Kowa Company, Ltd, Novartis Pharmaceuticals Corporation. D.J. Wexler: Other Relationship; Novo Nordisk. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate.
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