GLP-1 based therapies increase severe GI motility adverse events by 37% compared to SGLT-2 inhibitors

The increasing use of glucagon-like peptide-1 (GLP-1) based therapies for type-2 diabetes and weight management has raised questions about their full safety profile. While known to affect gastrointestinal motility (e.g., delayed gastric emptying), robust evidence on their association with severe motility-related adverse events, such as gastroparesis or intestinal obstruction, has been limited. Understanding these specific risks is crucial for clinicians to conduct comprehensive risk-benefit assessments and for patient counseling, especially given the widespread adoption of these powerful metabolic agents.

This new-user active-comparative cohort study analyzed two de-identified US commercial healthcare databases. Researchers identified adults with type-2 diabetes who initiated either GLP-1 based therapies (GLP-1 receptor agonists or tirzepatide) or sodium-glucose co-transporter 2 inhibitors (SGLT-2i), excluding those with prior major gastrointestinal conditions. The study involved 313,342 matched pairs after propensity score matching. The primary endpoint was a composite of severe constipation, gastroparesis, and gastrointestinal obstruction, with incidence rates and hazard ratios (HRs) estimated.

Among 313,342 matched pairs (mean age 60 years; 45% female) followed for a median of 5.2 months, the incidence rate of the composite outcome was 1.02 per 100 person-years for GLP-1 based therapies versus 0.75 per 100 person-years for SGLT-2i initiators. This translated to a rate difference of 0.27 per 100 person-years. The risk was significantly higher among GLP-1 based therapies initiators: > Initiators of GLP-1 based therapies faced a 37% higher risk (HR 1.37, 95% CI 1.30, 1.45) of severe gastrointestinal motility adverse events compared to SGLT-2i users. This increased risk was consistent across all individual components of the composite outcome. Importantly, this relative risk remained consistent across subgroups stratified by specific GLP-1 based therapy agent, age, sex, BMI, frailty level, diabetes severity, and opioid use, indicating broad applicability of the finding.