GLP-1 receptor agonists and cardiovascular events in metabolically healthy or unhealthy obesity

Aims: The associations of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and outcomes among patients with obesity according to the presence of cardiovascular risk factors (metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUHO)) remain unclear. We examined the associations of GLP-1RAs with mortality and adverse cardiovascular events in patients with MHO and MUHO. Methods: The TriNetX network was utilized to select a cohort of patients with MHO or MUHO, and use or non-use of GLP-1RAs with propensity score matching (1:1). Cardiovascular events were identified during follow-up. Results: A total of 2 983 151 patients with obesity (512 434 with MHO and 2 470 717 with MUHO) were included in the study. Among these, 416 713 (13.9%) were GLP-1RA users. After propensity score matching, GLP-1RA use in MUHO was associated with a significantly lower risk of mortality (HR 0.580 [95% CI, 0.566-0.595]), ischemic stroke (HR 0.921 [0.890-0.953]), AF (HR 0.913 [0.888-0.938]) and hospitalization for HF (HR 0.925 [0.900-0.949]) during follow-up compared with non-use of GLP-1RA. Patients with MHO had a markedly lower risk of clinical events than those with MUHO. A trend towards a lower risk of cardiovascular events associated with GLP-1RA was seen among patients with MHO. There was no statistical interaction in the risk of cardiovascular outcomes with GLP-1RA use for MHO and MUHO patients. Conclusions: The use of GLP-1RAs was associated with lower rates of cardiovascular events than no use in patients with MUHO. Similar but non-statistically significant trends were seen in patients with MHO.