The effects of glucagon-like peptide 1 agonists on immune checkpoint inhibitor-associated cardiotoxicity

BackgroundImmune checkpoint inhibitors (ICIs) have improved the survival outcomes of cancer but are also associated with major adverse cardiovascular events (MACE). Glucagon-like peptide 1 agonists (GLP1a) have been shown to reduce MACE in the non-cancer population; however, there is no data testing whether GLP1a reduces the risk for MACE associated with ICIs.MethodsWe conducted a retrospective, propensity score-matched cohort study using the TriNetX Analytics Network database, which contains de-identified data from over 120 participating healthcare institutions. We included all adult cancer patients with type 2 diabetes mellitus (T2DM) who were treated with an ICI. We matched patients on a GLP1a with patients on non-GLP1a diabetes medications, respectively. We excluded patients with a history of MACE to focus on the role of GLP1a in the primary prevention of MACE. The primary efficacy outcome was MACE, defined as a composite of heart failure, myocardial infarction, and myocarditis and individual components of MACE. The safety outcomes included all-cause mortality and adverse events of special interest that have been associated with the use of GLP1a.ResultsWe matched 392 patients on a GLP1a with patients on non-GLP1a diabetes medications. The most common indication for an ICI was lung cancer (24%) and the most commonly used ICI was pembrolizumab (51%). In Cox proportional hazards analyses, GLP1a were associated with a lower risk of MACE (Hazard ratio (HR), 0.33 [95% CI: 0.18-0.63]) and heart failure (HR, 0.38 [95% CI: 0.18-0.79]). Patients on a GLP1a also had a lower rate of all-cause mortality than those on a non-GLP1a (HR, 0.49 [95% CI: 0.36-0.66]) without an increase in safety events. Table: 1891P Outcomes Hazard ratio (95% CI) Efficacy outcomes MACE 0.33 (0.18-0.63) Heart failure 0.38 (0.18-0.79) Myocardial infarction 0.20 (0.07-0.58) Myocarditis 0.47 (0.04-5.20) Safety outcomes All-cause mortality 0.49 (0.36-0.66) Pancreatitis 1.06 (0.36-3.17) Biliary disease 0.34 (0.15-0.77) Bowel obstruction 0.48 (0.21-1.08) Gastroparesis 1.39 (0.23-8.34) ConclusionsThe use of GLP1a was associated with a reduction in MACE, heart failure, and all-cause mortality among cancer patients receiving ICIs without an increase in adverse events.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureT.G.N. Neilan: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Genentech, Roivant, Roche, Sanofi, Race Oncology, C4 Therapeutics, CardiolRx, and CRC Oncology; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Abbott, and AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: National Institutes of Health/NHLBI. All other authors have declared no conflicts of interest.