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Comparative Study
. 2021 Feb 11;20(1):39.
doi: 10.1186/s12933-021-01243-4.

SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system

Benedetta Maria Bonora  1 , Emanuel Raschi  2 , Angelo Avogaro  1 , Gian Paolo Fadini  3
Affiliations
Comparative Study

SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system

Benedetta Maria Bonora et al. Cardiovasc Diabetol. .

Abstract

Background: Sodium glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of heart failure and new data show they can prevent atrial fibrillation (AF). We examined the association between SGLT2i and AF in the Food and Drug Administration adverse event reporting system (FAERS).

Methods: We mined the FAERS from 2014q1 to 2019q4 to compare AF reporting for SGLT-2 i versus reports for other glucose lowering medications (ATC10 class). Several exclusions were sequentially applied for: concomitant medications; diabetes, cardiovascular or renal disease indication; reports for competing adverse events (genitourinary tract infections, ketoacidosis, Fournier's gangrene, amputation). We provide descriptive statistics and calculated proportional reporting ratios (PRR).

Results: There were 62,098 adverse event reports for SGLT2i and 642,031 reports for other ATC10 drugs. The reporting of AF was significantly lower with SGLT2i than with other ATC10 drugs (4.8 versus 8.7/1000; p < 0.001) with a PRR of 0.55 (0.49-0.62). Results did not change substantially after excluding reports listing insulin (PRR 0.49) or anti-arrhythmics (PRR 0.59) as suspect or concomitant drugs, excluding reports with indications for cardiovascular disease (PRR 0.49) or renal disease (PRR 0.55), and those filed for competing adverse events (PRR 0.63). Results were always statistically significant whether the diabetes indication was specified. Negative and positive controls confirmed internal validity of the database.

Conclusions: In a large pharmacovigilance database, AF was robustly and consistently reported more frequently for diabetes medications other than SGLT2i. This finding complements available evidence from trials supporting a protective role of SGLT2i against the occurrence of AF.

Keywords: Clinical practice; Complications; Epidemiology; Observational; Pharmacovigilance; Type 2 diabetes.

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Conflict of interest statement

BMB received lecture or advisory board fees from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Mundipharma, Novartis, Novo Nordisk, and Sanofi. AA received research grants, lecture or advisory board fees from: Merck Sharp & Dome, AstraZeneca, Novartis, Boehringer-Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Lilly, Servier, and Takeda. GPF received grants, honoraria or lecture fees from Abbott, Astrazeneca, Boehringer, Lilly, Novo Nordisk, Sanofi. ER has no competing interests.

Figures

Fig. 1
Fig. 1
Study flow chart. A series of interconnected analyses is reported, with progressive exclusions. FAERS, FDA adverse event reporting system. SGLT2i, sodium glucose cotransporter-2 inhibitors. ATC anatomical therapeutic classification, AE adverse event, CVD cardiovascular disease, RD renal disease, GUTI genito-urinary tract infections, DKA diabetic ketoacidosis, FG Fournier’s gangrene. Numbers are referred to the total number or reports in each analysis (*with the diabetes indication)
Fig. 2
Fig. 2
Case demographics. Key characteristics of the AF reports are shown: age category (a), sex (b), drug role (c), reporting source (d). SGLT2i, sodium glucose cotransporter-2 inhibitors. ATC anatomic therapeutic classification, HCP health care professional. Numbers inscribed within stacked bars are percentages
Fig. 3
Fig. 3
Disproportionality analysis. The Forest plot shows proportional reporting ratios (PRR) with 95% confidence intervals (CI) for atrial fibrillation (AF) in reports for sodium glucose cotransporter-2 inhibitors (SGLT2i) versus control drugs. A PRR < 1.0 indicates a disproportional lower rate of AF among reports for SGLT2i. ATC anatomic therapeutic classification, AE adverse event, CVD cardiovascular disease, RD renal disease
See this image and copyright information in PMC

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