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Nutr Metab Cardiovasc Dis. 2018 Jun;28(6):533-542. doi: 10.1016/j.numecd.2018.02.014. Epub 2018 Mar 1.

Pharmacovigilance of sodium-glucose co-transporter-2 inhibitors: What a clinician should know on disproportionality analysis of spontaneous reporting systems.

Author information

1
Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
2
Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. Electronic address: elisabetta.poluzzi@unibo.it.
3
University of Bordeaux, U657, 33000, Bordeaux, France; INSERM U657, 33000, Bordeaux, France; CIC Bordeaux CICI1401, 33000, Bordeaux, France.
4
Unit of Metabolic Diseases & Clinical Dietetics, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
5
Department of Public Health and Community Medicine, University of Verona, Verona, Italy.

Abstract

Sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) have consistently demonstrated a clinically significant reduction of cardiovascular mortality. However, their safety in clinical practice is still incompletely characterized, and post-marketing monitoring is required considering the expected increase in clinical use. Different analyses of international spontaneous reporting systems, known as disproportionality analyses (DAs), have highlighted the occurrence of ketoacidosis, amputations, acute renal failure and skin toxicity. In this viewpoint, we critically appraise these pharmacovigilance data on SGLT2-Is, with the aim of supporting clinicians in proper interpretation of these studies, and discussing their risk-benefit profile. To this aim, we offer a broad perspective on basic technical aspects subtending DAs of spontaneous reporting databases (describing peculiarities of the Food and Drug Administration Adverse Event Reporting System), their common and evolving uses, key pitfalls in presenting study results (in terms of "risk" or "association") and relevant strategies to account for major confounders. This will also facilitate reviewers and editors in proper evaluation of DAs, and prompt pharmacovigilance experts in converging towards a set of minimum requirements in standardization of design, performance and reporting of DAs. A consensus on quality assessment of DAs will finally establish their transferability to clinical practice. It is anticipated that DAs cannot be used per se as a standalone approach to assess a drug-related risk and cannot replace clinical judgment in the individual patient.

KEYWORDS:

Disproportionality; FAERS; Pharmacovigilance; Signal; Sodium-glucose co-transporter-2 inhibitors

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