PCSK9 Inhibitors Associated Hyperglycemic Disorders: A Real World, Pharmacovigilance Study
2Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel, Israel
3Pharmacology Unit, Department of Medical and Surgical Sciences,, Alma Mater Studiorum, University of Bologna, Bologna, Italy, Italy
4Division of Endocrinology & Metabolism, The Chaim Sheba Medical Center, Tel-Hashomer, Israel, Israel
5Department of Epidemiology and Preventive Medicine, School of Public Health, Tel-Aviv University, Tel-Aviv, Israel, Israel
6Unit for Cardiovascular Epidemiology,, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel HaShomer, Israel., Israel
7Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA, USA
8Leviev Heart Center, Sheba Medical Center, Tel HaShomer, Israel., Israel
Background: Initial genetic and biological studies indicated an association between proprotein-convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and hyperglycemic disorders. However, subsequent clinical trials yielded inconsistent results, and real-world data are scant.
Purpose: We sought to assess the association of PCSK9i and hyperglycemic events in a real-world setting, using the FDA adverse event reporting system (FAERS).
Methods: The FAERS database (2015-2020) was retrospectively queried to assess reporting of PCSK9i-associated hyperglycemic events. Disproportionality analyses were performed using an adjusted odds ratio (adj.ROR), and the lower bound of the information component (IC) 95% credibility interval (IC025>0 is deemed significant).
Results: The full database included 7,295,624 eligible patients, among them 71,748 reports of evolocumab and 15,976 of alirocumab. Compared to the full database, treatment with evolocumab, but not alirocumab, was associated with increased reporting of hyperglycemic events (n=1,587[2.21%], adj.ROR=1.24 [1.15-1.32], IC025=0.20; n=254[1.59%], adj.ROR=0.73 [0.60-0.88], IC025=-0.38, respectively). Hyperglycemic events were primarily mild hyperglycemic disorders (n=1,262[1.76%], adj.ROR=1.56 [1.42-1.71], IC025=0.58), whereas diabetes was not over-reported (n=325[0.45%], adj.ROR=0.73 [0.63-0.86], IC025=-0.82). Hyperglycemic events were over-reported with evolocumab versus ezetimibe (adj.ROR=1.81 [1.06−3.07]), albeit were less frequently reported versus statins (adj.ROR=0.44 [0.40−0.49]). Most of the hyperglycemic events occurred during the first six months of treatment and were reversible.
Conclusion: In a real-world setting, evolocumab (but not alirocumab) was consistently associated with mild hyperglycemic disorders, but not diabetes. Although initial monitoring is warranted, the favorable glycemic safety profile compared to statins supports their essential role in the management of lipid disorders. Potential different effects of evolocumab and alirocumab on glucose metabolism should be further evaluated prospectively.
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