Context SGLT2is are first-line antidiabetic agents with demonstrated cardiovascular benefits. Prior meta-analyses have examined adverse events (AEs) associated with these drugs in general, but such knowledge needs to be updated with the results of more recent trials. In addition, the occurrence of various AEs with different underlying diseases is unknown. Objective This meta-analysis aimed to investigate the occurrence of various AEs associated with sodium–glucose cotransporter 2 inhibitors (SGLT2is) and to examine the level of risk of AEs in patients with different underlying diseases. Methods We conducted a quantitative meta-analysis of randomized controlled trials (RCTs) retrieved from the MEDLINE and EMBASE databases and the Cochrane library on January 31, 2021. Outcomes of interest included 4 overall safety outcomes (AEs) and 12 specified safety outcomes. Further analyses were performed on various subgroups, which were defined based on the status of diabetes mellitus (DM), atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease, and congestive heart failure, and by the dosage of SGLT2i (high dose vs low dose). Results Our analysis included 10 eligible studies with a total of 71 553 participants. The meta-analysis showed that SGLT2i led to increased risks of genital infection (risk ratio [RR] 3.56, 95% CI 2.84-4.46), urinary tract infection (RR 1.06, 95% CI 1.00-1.12), diabetic ketoacidosis (RR 2.23, 95% CI 1.36-3.63), and volume depletion (RR 1.14, 95% CI 1.06-1.23). However, the use of SGLT2i was associated with reduced risks of any serious AE (RR 0.92, 95% CI 0.90-0.94), acute kidney injury (AKI) (RR 0.84, 95% CI 0.77-0.91), and hyperkalemia (RR 0.84, 95% CI 0.72–0.99). Within the different subgroups, the risk of amputation was higher in patients with ASCVD than in those without (RR 1.44 vs 0.96, P = .066). Conclusion The use of SGLT2is is generally safe. SGLT2is may be associated with increased risks of genital infection but are protective against AKI. Of note, the risk of amputation was higher in patients with ASCVD. The key to the safe use of SGLT2is lies in the identification of high-risk populations and close surveillance of patients after treatment.

Background: Symptoms of heart failure with preserved left ventricular systolic function are common among patients undergoing peritoneal dialysis (PD). Epicardial fat (EpF) is an ectopic fat depot with possible paracrine or mechanical effects on myocardial function. The aim of our current study is to assess the association between EpF and Left ventricular diastolic dysfunction (LVDD) in patients undergoing PD and to clarify the relationships among EpF, inflammation, and LVDD in this population. Methods: This was a cross-sectional study of 149 patients with preserved left ventricular systolic function who were undergoing PD. LVDD was diagnosed (according to the European Society of Cardiology guidelines) and EpF thickness measured by echocardiography. The patients without LVDD were used as controls. The serum inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) was measured. The location and amount of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Results: Subjects with LVDD had higher levels of hsCRP, more visceral and peritoneal fat, and thicker EpF (all p < 0.001) than controls. Visceral adipose tissue, hsCRP, and EpF all correlated significantly (p < 0.05) with LVDD. Multivariate regression analysis rendered the relationship between visceral adipose tissue and LVDD insignificant, whereas EpF was the most powerful determinant of LVDD (odds ratio = 2.41, 95% confidence interval = 1.43–4.08, p < 0.01). EpF thickness also correlated significantly with the ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e’; r = 0.27, p < 0.01). Conclusion: EpF thickness is significantly independently associated with LVDD in patients undergoing PD and may be involved in its pathogenesis.

Background: Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain. Methods and Results: This meta‐analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta‐analysis. High‐ and low‐dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High‐dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low‐dose regimens, with both doses having similar bleeding risks. Conclusions: In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban. Registration: URL: www.crd.york.ac.uk/prospero/ . Unique identifier: CRD42022329557.