Gastrointestinal effects compared across GLP-1 drugs in real-world study

Dulaglutide, semaglutide, and tirzepatide have similar gastrointestinal safety profiles, a matched cohort analysis found.

The study used a U.S. insurance database to make pairwise comparisons of three groups: patients with type 2 diabetes who initiated dulaglutide, subcutaneous semaglutide, or tirzepatide in 2019 to 2024. The primary outcome was a composite of acute pancreatitis, biliary disease, bowel obstruction, gastroparesis, and severe constipation. Patients were matched one-to-one based on propensity score. Results were published by Annals of Internal Medicine on Nov. 4.

Between the 65,238 matched pairs in the semaglutide versus dulaglutide cohort, the 20,893 in the tirzepatide versus dulaglutide cohort, and the 46,620 in the tirzepatide versus semaglutide cohort, there were no significant differences on the composite outcome (hazard ratios [HRs], 0.96 [95% CI, 0.87 to 1.06], 0.96 [95% CI, 0.77 to 1.20], and 1.07 [95% CI, 0.90 to 1.26], respectively). The findings were consistent when the outcomes were considered individually and in subgroup and sensitivity analyses. However, in a sensitivity analysis that used sodium-glucose cotransporter-2 inhibitors as the comparator, gastrointestinal adverse events were higher with semaglutide (HR, 1.22; 95% CI, 1.09 to 1.37), tirzepatide (HR, 1.53; 95% CI, 1.21 to 1.93), and dulaglutide (HR, 1.36; 95% CI, 1.21 to 1.53),

“Overall, the results of this study align with evidence from head-to-head [randomized controlled trials], which showed similar gastrointestinal safety profiles for the 3 medications,” said the study authors. “Our study complements existing information by providing meaningful real-world evidence on the risk for severe gastrointestinal events in users of [glucagon-like peptide-1 receptor agonists] or tirzepatide in routine clinical practice.”

Limitations of the study include the possibility of residual confounding by glycemic control and body mass index.