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Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001 were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.

Heart failure (HF) is a chronic disorder that decreases heart function and causes a person to be less tolerant to exercise, have a lower quality of life, and prone to death. Novel therapeutic strategies are still needed despite improvements in HF management. Sotagliflozin is a promising medication for the treatment of HF, which is a dual sodium-glucose cotransporter 1 as well as 2 (SGLT1 and SGLT2) inhibitor. The purpose of this in-depth study is to assess sotagliflozin's effectiveness and safety in the treatment of HF. The effects of sotagliflozin on different facets of HF pathophysiology, such as blood flow, myocardial remodeling, and neurohormonal stimulation, are discussed in preclinical and clinical investigations. Sotagliflozin has been shown to be effective in lowering the risk of HF hospitalization and heart attack in patients with HF with either type 2 diabetic mellitus (T2DM) and chronic kidney disease (CKD), according to numerous randomized trials, including the most recent SOLOIST-WHF or SCORED trials. Sotagliflozin's simultaneous inhibition of SGLT1 along with SGLT2 creates a special pharmacological profile that addresses both the metabolic as well as non-metabolic problems seen in HF. This review provides a comprehensive summary of various aspects related to sotagliflozin and heart failure, including the pathophysiology in heart failure, US-FDA approved treatment for HF, mechanism of action, pharmacokinetic, pharmacodynamics data of sotagliflozin, reported adverse drug reactions (ADRs), and ongoing clinical trials.

Objective: Sotagliflozin is a dual sodium-glucose co-transporter-1 and 2 (SGLT1/2) inhibitor with selectivity towards SGLT2. Previous studies showed that SGLT2 inhibitors can improve cardiac function and reduce myocardial infarction size in animal models of myocardial infarction (MI). However, it remains unknown whether the dual inhibition of SGLT1/2 by sotagliflozin has beneficial effects in this context. In this study, we investigated the potential cardioprotective effects of sotagliflozin in an animal model of MI. Methods: Sprague Dawley (SD) rats underwent left anterior descending coronary artery ligation or sham ligation then were randomly assigned to receive either sotagliflozin (10 mg/kg) or vehicle via intraperitoneal injection. Fourteen days post-MI, we assessed cardiac function using echocardiography and evaluated histological and molecular markers of cardiac remodeling and inflammation in the left ventricle. Results: Our findings indicate that sotagliflozin treatment resulted in improved cardiac function and reduced infarct size compared with the vehicle-treated group. Additionally, sotagliflozin improved cardiac remodeling as shown by the decreased cardiac hypertrophy and cardiac apoptosis in the post-MI heart. Mechanistically, an apparent reduction in the cardiac inflammatory response in sotagliflozin-treated hearts was observed in the post-MI rats. Conclusion: Overall, our results suggest that sotagliflozin may have cardioprotective effects against myocardial infarction.

Aim: To provide a pooled effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF: ≥50%) or/and mildly reduced EF (HFmrEF: 41–49%) regardless of baseline diabetes. Methods: We systemically searched PubMed/MEDLINE, Embase, Web of Science databases and clinical trial registries using appropriate keywords till August 28, 2022, to identify randomized controlled trials (RCTs) or post-hoc analysis of RCTs, reporting cardiovascular death (CVD) and/or urgent visits/hospitalization for heart failure(HHF) in patients with HFmrEF/HFpEF receiving SGLTi vs. placebo. Hazard ratios (HR) with 95% confidence intervals (CI) for outcomes were pooled together using generic inverse variance method with fixed-effects model. Results: We identified six RCTs, pooling data retrieved from 15,769 patients with HFmrEF/HFpEF. Pooled analysis showed that compared to placebo, SGLT2i use was significantly associated with improved CVD/HHF outcomes in HFmrEF/HFpEF (pooled HR 0.80, 95% CI: 0.74, 0.86, p

Cystic fibrosis (CF) is a lethal autosomal-recessive inherited disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the present work, we derived human proximal lung organoids (HLOs) from patient-derived pluripotent stem cells (PSCs) carrying disease-causing CFTR mutations. We evaluated the forskolin (Fsk)-stimulated swellings of these HLOs in the presence of CFTR modulators (VX-770 and/or VX-809) and demonstrated that HLOs respond to CFTR modulators in a mutation-dependent manner. Using this assay, we examined the effects of the sodium-dependent glucose cotransporter 1/2 (SGLT1/2) inhibitor drugs phlorizin and sotagliflozin on the basis of our findings that SGLT1 expression is upregulated in CF HLOs and airway epithelial cells compared with their wild-type counterparts. Unexpectedly, both drugs promoted dF/dF HLO swelling. These results reveal SGLTs, especially SGLT1, as potential therapeutic targets for treating CF lung diseases and demonstrate the use of PSC-derived HLOs as a preclinical tool in CF drug development.

Despite the risk of atherosclerosis has progressively declined over the past few decades, subjects with type 2 diabetes mellitus (T2DM) continue to experience substantial excess of atherosclerotic cardiovascular disease (ASCVD)-related events. Therefore, there is urgent need to treat ASCVD disease in T2DM earlier, more intensively, and with greater precision. Many factors concur to increase the risk of atherosclerosis, and multifactorial intervention remains the basis for effective prevention or reduction of atherosclerotic events. The role of anti-hyperglycemic medications in reducing the risk of ASCVD in subjects with T2DM has evolved over the past few years. Multiple cardiovascular outcome trials (CVOTs) with new and emerging glucose-lowering agents, namely SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1-RA), have demonstrated significant reductions of major cardiovascular events and additional benefits. This robust evidence has changed the landscape for managing people with T2DM. In addition to glycemic and ancillary extra-glycemic properties, SGLT2i and GLP1-RA might exert favorable effects on subclinical and clinical atherosclerosis. Therefore, the objective of this review is to discuss the available evidence supporting anti-atherosclerotic properties of SGLT2i and GLP1-RA, with a quick nod to sotagliflozin and tirzepatide., Competing Interests: Declaration of competing interest Angela Dardano (AD) reported no duality of interest. Cristina Bianchi (CB) reported consulting fees and grants from Lilly, Novo Nordisk, Merck Sharp & Dohme Corp. Monia Garofolo (MG) reported consulting fees from Novo Nordisk, Eli Lilly, Merck Sharp & Dohme Corp. and Bayer Inc. Stefano Del Prato (SDP) has served as president of EASD/European Foundation for the Study of Diabetes (EFSD) (2020–2022); has received research grants to the institution from AstraZeneca and Boehringer Ingelheim; has served as advisor for Abbott, Amarin Corporation, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., EvaPharma, Jiangsu Hengrui Pharmaceuticals Co., Menarini International, Merck Sharpe & Dohme, Novartis Pharmaceutical Co., Novo Nordisk, Sanofi and Sun Pharmaceuticals; and has received fees for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Laboratori Guidotti, Menarini International, Merck Sharpe & Dohme, and Novo Nordisk. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Approximately 25% of patients admitted to hospitals for worsening heart failure (WHF) are readmitted within 30 days., Objectives: The authors conducted a post hoc analysis of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post-WHF) trial to evaluate the efficacy of sotagliflozin versus placebo to decrease mortality and HF-related events among patients who began study treatment on or before discharge from their index hospitalization., Methods: The main endpoint of interest was cardiovascular death or HF-related event (HF hospitalization or urgent care visit) occurring within 90 and 30 days after discharge for the index WHF hospitalization. Treatment comparisons were by proportional hazards models, generating HRs, 95% CIs, and P values., Results: Of 1,222 randomized patients, 596 received study drug on or before their date of discharge. Sotagliflozin reduced the main endpoint at 90 days after discharge (HR: 0.54 [95% CI: 0.35-0.82]; P = 0.004) and at 30 days (HR: 0.49 [95% CI: 0.27-0.91]; P = 0.023) and all-cause mortality at 90 days (HR: 0.39 [95% CI: 0.17-0.88]; P = 0.024). In subgroup analyses, sotagliflozin reduced the 90-day main endpoint regardless of sex, age, estimated glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, left ventricular ejection fraction, or mineralocorticoid receptor agonist use. Sotagliflozin was well-tolerated but with slightly higher rates of diarrhea and volume-related events than placebo., Conclusions: Starting sotagliflozin before discharge in patients with type 2 diabetes hospitalized for WHF significantly decreased cardiovascular deaths and HF events through 30 and 90 days after discharge, emphasizing the importance of beginning sodium glucose cotransporter treatment before discharge., Competing Interests: Funding Support and Author Disclosures This study was supported by Sanofi and Lexicon Pharmaceuticals. Dr Pitt has received consulting fees from Lexicon, Bayer, AstraZeneca, Boehringer Ingelheim, Merck, and Phasebio; has received consulting fees and/or stock options from Viror, KBP Biosciences, Cereno Scientific, Tricida, SCPharmaceuticals, SQinnovatiions, G-3 Pharmaceuticals, Protonintel, and Brainstorm medical; holds U.S. Patent 9931412 on site specific delivery of eplerenone to the myocardium; and U.S. Patent pending 63/045,783 on histone-modulating agents for the protection and treatment of organ damage. Dr Bhatt is the Chair of SOLOIST with research funding paid by Lexicon to Brigham and Women’s Hospital; he is on the Advisory Board for AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; is on the Board of Directors for AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; is Inaugural Chair for the American Heart Association Quality Oversight Committee; is a consultant for Broadview Ventures; is on the Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; is on the RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; is on the AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned it to Lexicon; neither he nor Brigham and Women’s Hospital receive any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); is site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; is a trustee for the American College of Cardiology; and has done unfunded research for FlowCo and Takeda. Dr Szarek has received salary support from CPC, a nonprofit academic research organization affiliated with the University of Colorado, that receives research grant/consulting funding from Abbott, Agios, Alexion Pharma, Alnylam, Amgen, Angionetics, ARCA Biopharma, Array, AstraZeneca, Atentiv, Audentes, Bayer, Better Therapeutics, Brigham and Women’s Hospital, Bristol-Myers Squibb, Cardiol Therapeutics, CellResearch, Cook Medical, Cook, CSL Behring, Eidos Therapeutics, EP Trading Co, Esperion Therapeutics, Everly Health, Faraday, Fortress Biotech, HDL Therapeutics, Heartflow, Hummingbird Bioscience, Insmed, Janssen, Kowa Research, Lexicon, Merck, MedPace, Medtronic, Moderna, Novate Medical, NovoNordisk, Pfizer, PhaseBio, PPD Development, Prairie Education and Research, Prothena Biosciences, Regeneron, Regio Biosciences, Sanifit Therapeutics, Sanofi, Smith and Nephew, Stealth BioTherapeutics, University of Colorado, University of Pittsburgh, Worldwide Clinical Trials, Wraser, and the Yale Cardiovascular Research Group; has received fees for performing analyses, steering committee fees, and travel support from Sanofi and Regeneron; has received consulting fees from CiVi, Esperion, and Amarin; has received Data Safety and Monitoring Board membership fees from Resverlogix and Janssen; and is a member of the JACC editorial board. Dr Cannon has received research grants from Amgen, Better Therapeutics, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Merck, Novo Nordisk, Pfizer; consulting fees from Aegerion/Amryt, Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, Lexicon, Merck, Pfizer, Rhoshan, and Sanofi; and service on the Data and Safety Monitoring Boards for the Veteran’s Administration, Applied Therapeutics, and NovoNordisk. Dr Leiter has received research funding from, has provided CME on behalf of, and/or has acted an adviser to AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Lexicon, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Servier. Dr McGuire has received honoraria for trial leadership from Lexicon, Sanofi, Boehringer Ingelheim, Merck & Co, Pfizer, AstraZeneca, Novo Nordisk, Esperion, Lilly USA, CSL Behring; and has received honoraria for consultancy from Lilly USA, Boehringer Ingelheim, Novo Nordisk, CSL Behring, Bayer, GlaxoSmithKline, and Lexicon. Dr Lewis has received consultant fees from Sanofi. Dr Riddle has received honoraria for consulting from Adocia, Anji, Xeris, DalCor, and Theracos. Dr Voors has received consultancy and speaker fees and research support from AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, BMS, Cyrokinetics, Merck, Myokardia, Novartis, NooNordisk, and Roche diagnostics. Dr Metra has received personal fees from Actelion, Amgen, Livanova, and Vifor pharma as a member of Executive or Data Monitoring Committees of sponsored clinical trials; from AstraZeneca, Bayer, Boheringer Ingelhelm, Edwards Lifesciences, Novartis for participation in advisory boards and/or speeches at sponsored meetings. Dr Lund has received support from the Karolinska Institutet, the Swedish Research Council [grant 523-2014-2336], and the Swedish Heart Lung Foundation [grants 20150557, 20190310] and grants from AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, Novartis, and MSD; consulting honoraria from Vifor, AstraZeneca, Bayer, Pharmacosmos, MSD, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, Servier, Edwards Lifesciences, and Alleviant; and speaker honoraria from Abbott, OrionPharma, MedScape, Radcliffe, AstraZeneca, Novartis, Boehringer Ingelheim, and Bayer; and has patents with AnaCardio and stock ownership in AnaCardio. Dr Komajda has received honoraria from Servier, Novartis, Boehringer Ingelheim, AstraZeneca, Bayer, and Sanofi as adviser/member of clinical trials committees. Dr Testani has received grants and/or personal fees from 3ive labs, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, AstraZeneca, Novartis, Cardionomic, MagentaMed, Reprieve Inc, FIRE1, W. L. Gore & Associates, Sanofi, Sequana Medical, Otsuka, Abbott, Merck, Windtree Therapeutics, Lexicon pharmaceuticals, Precardia, Relypsa, Regeneron, BD, Edwards Lifesciences, and Lilly; and has a patent treatment of diuretic resistance issued to Yale and Corvidia Therapeutics Inc, a patent methods for measuring Renalase issued to Yale, and a patent treatment of diuretic resistance pending with Reprieve Inc. Dr Ponikowski has received consultancy fees and speaker honoraria from Boehringer Ingelheim, AstraZeneca, Vifor Pharma, Amgen, Servier, Novartis, Bayer, MSD, Pfizer, Impulse Dynamics, Renal Guard Solutions, BMS, AbbottVascular, and the Radcliffe Group. Dr Lopes has received research grants or contracts from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi-Aventis; funding for educational activities or lectures from Pfizer, Daiichi Sankyo, and Novo Nordisk; and funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Novo Nordisk. Dr Ezekowitz has received research support for trial leadership from Bayer, Merck & Co, Novo Nordisk, Cytokinetics, Applied Therapeutics, American Regent; and honoraria for consultancy from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Otsuka, Bayer, and Novartis. Dr Davies and Mr Sun are employed by and may have stock or stock options in Lexicon Pharmaceuticals, Inc. Dr Verma has received research and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, CMS, HLS, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, and Sanofi; and is the President of the Canadian Medical and Surgical Knowledge Translation Research Group and holds the Tier 1 Canada Research Chair in Cardiovascular Surgery. Dr Kosiborod has received research grants from AstraZeneca and Boehringer Ingelheim; served as a consultant or advisory board member for Alnylam, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Sanofi, Vifor Pharma; has received other research support from AstraZeneca; and honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr Steg has received research grants from Amarin, Bayer, Sanofi, and Servier; speaker or consultant fees from Amarin, Amgen, AstraZeneca, Bayer, Bristol-Myers-Squibb, Janssen, Kowa, Idorsia, Lexicon, Merck, Novartis, Novo-Nordisk, PhaseBio, Pfizer, Regeneron, Sanofi, Servier; and is a Senior Associate Editor of Circulation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To provide a pooled effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF: ≥50%) or/and mildly reduced EF (HFmrEF: 41-49%) regardless of baseline diabetes., Methods: We systemically searched PubMed/MEDLINE, Embase, Web of Science databases and clinical trial registries using appropriate keywords till August 28, 2022, to identify randomized controlled trials (RCTs) or post-hoc analysis of RCTs, reporting cardiovascular death (CVD) and/or urgent visits/hospitalization for heart failure(HHF) in patients with HFmrEF/HFpEF receiving SGLTi vs. placebo. Hazard ratios (HR) with 95% confidence intervals (CI) for outcomes were pooled together using generic inverse variance method with fixed-effects model., Results: We identified six RCTs, pooling data retrieved from 15,769 patients with HFmrEF/HFpEF. Pooled analysis showed that compared to placebo, SGLT2i use was significantly associated with improved CVD/HHF outcomes in HFmrEF/HFpEF (pooled HR 0.80, 95% CI: 0.74, 0.86, p < 0.001, I 2  = 0%). When separately analyzed, benefits of SGLT2i remained significant across HFpEF (N = 8891, HR 0.79, 95% CI: 0.71, 0.87, p < 0.001, I 2  = 0%) and HFmrEF (N = 4555, HR 0.77, 95% CI: 0.67, 0.89, p < 0.001, I 2  = 40%). Consistent benefits were observed also in HFmrEF/HFpEF subgroup without baseline diabetes (N = 6507, HR 0.80, 95% CI: 0.70, 0.91, p < 0.001, I 2  = 0%). Sensitivity analysis including the DELIVER and EMPEROR-Preserved trials found a trend towards significant beneficial effects on CV deaths with no heterogeneity (HR 0.90, 95% CI: 0.79, 1.02, p = 0.08, I 2  = 0%)., Conclusions: This meta-analysis established the place of SGLT2i as a foundational therapy among patients with HF with preserved and mildly reduced EF regardless of diabetes., (Copyright © 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Aims: Sodium-glucose co-transporter inhibitors (SGLT2i) are emerging as a new treatment for heart failure (HF) after demonstrating favorable clinical outcomes in several randomized controlled trials (RCTs). In this meta-analysis, we assessed the safety of SGLT2i in the trials that prespecified heart failure in their inclusion criteria., Materials and Methods: We searched the databases for RCTs comparing SGLT2i to placebo in heart failure patients. The primary outcome was the incidence of serious adverse events (SAEs). A sensitivity analysis according to the class of HF was also performed., Results: The incidence of SAEs was significantly lower in the SGLT2i group (OR, 0.85; 95% CI, 0.77-0.92; P, 0.0002) and SAEs remained significantly lower after performing the sensitivity analysis (OR, 0.82; 95% CI, 0.75-0.89; P, <0.00001). Genital infections, urinary tract infections (UTIs), and hypotension were significantly higher in the SGLT2i group., Conclusions: SGLT2i remain a safe option for patients with HF with a lower incidence of SAEs. However, since they increase the risk of genital infection, UTIs and hypotension, the risks vs benefits in each patient should be weighed when making a prescribing decision., (Copyright © 2022 Elsevier B.V. All rights reserved.)