The following interview was conducted with Elisabetta Patorno, MD, corresponding author of the study published in Annals of Internal Medicine
Your study found higher GI adverse event rates in patients using insulin or recent opioids, though comparative treatment effects remained similar. Should gastroenterologists implement different monitoring or counseling protocols for these high-risk patients when consulted about GLP-1 RA/tirzepatide initiation?
Dr. Patorno: Our findings suggest heightened awareness rather than avoidance. The GI adverse events were more frequent among individuals using insulin or recent opioids, but importantly, the comparative risks between GLP-1 receptor agonists and tirzepatide were largely consistent across groups. When consulted on these high-risk patients, gastroenterologists should consider three practical approaches: First, provide anticipatory guidance about common GI effects, particularly for those already prone to delayed motility—for example, from opioid use. Second, consider a slower titration schedule and reinforce non-pharmacologic strategies such as hydration and smaller, low-fat meals. Third, encourage early follow-up to reassess tolerance. Overall, these findings point to the value of individualized monitoring rather than wholesale changes in prescribing or referral practices.
Your study excluded patients with prior gastroparesis, severe constipation, or biliary disease. When gastroenterologists are asked to risk-stratify patients with resolved or well-controlled GI conditions being considered for these medications, what guidance would you offer? Does your SGLT-2 inhibitor comparison (showing increased GI motility risks with all GLP-1 RAs/tirzepatide) suggest these should be preferred alternatives for such patients?
Dr. Patorno: Because we excluded individuals with history of gastroparesis, severe constipation, or biliary disease, caution is needed in extrapolating our results to these populations. For patients with previously resolved or well-controlled conditions, use of GLP-1 receptor agonists or tirzepatide may still be appropriate, though clinicians should conduct careful risk–benefit assessment and close observation for symptom recurrence, particularly early in treatment. Our comparative analyses do suggest that gastrointestinal motility-related events were more frequent with all GLP-1–based therapies than with SGLT-2 inhibitors. This could mean that, for patients with ongoing or unstable motility disorders, an SGLT-2 inhibitor might be a reasonable alternative, depending on their overall metabolic and cardiorenal profile. Ultimately, treatment decisions should remain individualized and collaborative, integrating the perspectives of gastroenterologists, endocrinologists, and other clinicians involved in the care process.
