LAUSR

Case reports and a pharmacovigilance analysis have linked glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with anaphylactic reactions, but real-world evidence for this possible association is lacking. Using databases from the United Kingdom (Clinical Practice Research Datalink) and United States (Medicare, Optum, MarketScan), we used a new-user, active comparator design where initiators of GLP-1 RAs were compared with two different active comparators (initiators of dipeptidyl peptidase-4 [DPP-4] inhibitors and initiators of sodium-glucose cotransporter-2 [SGLT-2] inhibitors) between 2007 and 2019. Propensity score fine stratification weighted Cox proportional hazards models were fit to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of anaphylactic reaction. Database-specific HRs were pooled using random-effects models. Compared with DPP-4 inhibitors (n=1,641,520), GLP-1 RAs (n=324,098) generated a modest increase in the HR for anaphylactic reaction with a wide CI (36.9 vs. 32.1 per 100,000, respectively; HR: 1.15, 95% CI: 0.94, 1.42). Compared with SGLT2 inhibitors (n=366,067), GLP-1 RAs (n=259,929) were associated with a 38% increased risk of anaphylactic reaction (40.7 vs. 29.4 per 100,000, respectively; HR: 1.38, 95% CI: 1.02, 1.87). In this large multi-site population-based cohort study, GLP-1 RAs were associated with a modest increased risk of anaphylactic reaction when compared with DPP-4 inhibitors and SGLT-2 inhibitors.