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Meta-Analysis
. 2024 Apr;11(2):637-648.
doi: 10.1002/ehf2.14633. Epub 2023 Dec 20.

Safety of sodium-glucose cotransporter 2 inhibitors drugs among heart failure patients: a systematic review and meta-analysis

Hamidreza Soleimani  1   2   3 , Behrad Saeedian  4 , Yeganeh Pasebani  5 , Nastaran Babajani  4 , Amirreza Pashapour Yeganeh  4 , Pegah Bahirai  6 , Hossein Navid  1   2 , Ahmad Amin  5 , Marc D Samsky  7 , Micheal G Nanna  7 , Kaveh Hosseini  1   2
Affiliations
Meta-Analysis

Safety of sodium-glucose cotransporter 2 inhibitors drugs among heart failure patients: a systematic review and meta-analysis

Hamidreza Soleimani et al. ESC Heart Fail. 2024 Apr.

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce morbidity and mortality for heart failure (HF) patients and are recommended as cornerstones for their medical therapy. Utilization in clinical practice remains low for multiple reasons, one of which may be adverse events. We investigated the incidence of these events to see if they are associated with SGLT2i use. A systematic search was performed in databases, including PubMed, Embase, Cochrane Library, Clinicaltrials.gov, and WHO's International Clinical Trials Registry Platform. Relevant randomized controlled trial studies assessing the safety outcomes of SGLT2i in HF patients were included in this study. We conducted the common-effect meta-analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of safety outcomes in SGLT2i compared with placebo. Eighteen studies were included in the meta-analysis composed of 12 925 HF patients taking an SGLT2i and 12 747 taking a placebo. The meta-analysis indicated that the all-cause mortality and serious adverse events (SAEs) were lower in the SGLT2i group (RR, 0.91; 95% CI, 0.85-0.97; P = 0.005, I2 = 0%; and RR, 0.92; 95% CI, 0.90-0.95; P < 0.001, I2 = 43%, respectively). Volume depletion and genitourinary infections were more prevalent in the SGLT2i group (RR, 1.17; 95% CI, 1.06-1.28; P = 0.001, I2 = 0%; and RR, 1.27; 95% CI, 1.13-1.43; P < 0.001, I2 = 17%, respectively). Our meta-analysis demonstrated that using SGLT2is in HF patients was correlated with reduced mortality and SAEs, with a more prominent effect in HF with reduced ejection fraction patients and those taking dapagliflozin.

Keywords: Heart failure; Meta‐analysis; SGLT2i; Safety outcomes; Sodium–glucose cotransporter‐2 inhibitors; Systematic review.

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Conflict of interest statement

Dr M.G.N. reports funding from the American College of Cardiology (George F and Ann Harris Bellows Foundation), the Patient‐Centered Outcomes Research Institute, and the National Institute on Aging/National Institutes of Health (GEMSSTAR award: R03AG074067); and consulting from HeartFlow, Inc. Other authors had nothing to disclose.

Figures

Central Illustration 1
Central Illustration 1
Graphical summary of the results.
Figure 1
Figure 1
PRISMA flow diagram of the included studies; search updated as of 1 March 2023.
Figure 2
Figure 2
Death events in groups of sodium–glucose cotransporter‐2 inhibitor (SGLT2i) recipients vs. placebo recipients in subgroups of different SGLT2i types. CI, confidence interval; RR, relative risk.
Figure 3
Figure 3
Death events in groups of sodium–glucose cotransporter‐2 inhibitor (SGLT2i) recipients vs. placebo recipients in subgroups of heart failure types. CI, confidence interval; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; RR, relative risk.
Figure 4
Figure 4
Serious adverse events in groups of sodium–glucose cotransporter‐2 inhibitor (SGLT2i) recipients vs. placebo recipients in subgroups of different SGLT2i types. CI, confidence interval; RR, relative risk.
Figure 5
Figure 5
Serious adverse events in groups of sodium–glucose cotransporter‐2 inhibitor (SGLT2i) recipients vs. placebo recipients in subgroups of heart failure types. CI, confidence interval; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; RR, relative risk.
See this image and copyright information in PMC

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