Glucagon-like peptide-1 (GLP-1) receptor agonists constitute a major group of drugs used to treat patients with type 2 diabetes. These drugs lower blood sugar levels and reduce body weight. However, whether these drugs cause life threatening allergies like anaphylactic reactions remains unclear. This is particularly concerning since the risk of allergic reactions is higher among patients with diabetes than in the general population. The current study will use the United Kingdom Clinical Practice Research Datalink to investigate whether the use of GLP-1 receptor agonists, compared with other antidiabetic drugs, increases the risk of anaphylactic reactions. This will provide much needed information regarding this possible association to patients and prescribers.
There is conflicting evidence in the literature regarding the association of GLP-1 receptor agonists and the risk of anaphylactic reactions. Indeed, GLP-1 receptor agonists are potentially immunogenic as they are protein-based molecules. Importantly, two of the approved GLP-1 receptor agonists, exenatide and lixisenatide, are structurally similar to exendin-4, an animal derived protein (hereafter called animal-based GLP-1 receptor agonists), while four other approved drugs of this class, liraglutide, dulaglutide, albiglutide, and semaglutide, are structurally similar to the human GLP-1 molecule (hereafter called human-based GLP-1 receptor agonists). To date, while several case reports of GLP-1 receptor agonist-associated anaphylactic reactions have been published in the literature, no observational study has been conducted to determine the association between GLP-1 receptor agonist use and anaphylactic reactions. Thus, this study will use the Clinical Practice Research Datalink to assemble a cohort of patients, at least 40 years of age, newly-treated with antidiabetic drugs between January 1, 2007 and January 31, 2019. Time-dependent Cox proportional hazards models will be used to estimate hazard ratios with 95% confidence intervals of anaphylactic reactions associated with animal-based or human-based GLP-1 receptor agonists compared with second- to third-line antidiabetic drugs. Secondary analyses will assess whether there is a duration-response relationship, and whether the risk varies by history of previous allergic conditions.
Health Outcomes to be Measured:
Anaphylactic reactions (Read codes and SNOMED-CT concept IDs outlined in Appendix 1).
HES Admitted Patient Care;ONS Death Registration Data