{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Automated"},"PMID":{"@attributes":{"Version":"1"},"@text":"41977354"},"DateCompleted":{"Year":"2026","Month":"04","Day":"14"},"DateRevised":{"Year":"2026","Month":"04","Day":"14"},"Article":{"@attributes":{"PubModel":"Electronic"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Electronic"},"@text":"1422-0067"},"JournalIssue":{"@attributes":{"CitedMedium":"Internet"},"Volume":"27","Issue":"7","PubDate":{"Year":"2026","Month":"Mar","Day":"31"}},"Title":"International journal of molecular sciences","ISOAbbreviation":"Int J Mol Sci"},"ArticleTitle":"Impact of SGLT2 Inhibitors on Mortality Across Different Populations: A Systematic Review and Meta-Analysis.","ELocationID":[{"@attributes":{"EIdType":"pii","ValidYN":"Y"},"@text":"3168"},{"@attributes":{"EIdType":"doi","ValidYN":"Y"},"@text":"10.3390\/ijms27073168"}],"Abstract":{"AbstractText":["Sodium-glucose cotransporter-2 (SGLT2) inhibitors offer glucose-lowering, cardio-protective and reno-protective properties. Mortality rates constitute a central endpoint for understanding the overall clinical value of SGLT2 inhibitors. This systematic review and meta-analysis aims to compare mortality outcomes associated with SGLT2 inhibitors across different populations. A systematic search was performed in four databases-PubMed, Scopus, Web of Science (WOS) and Cochrane CENTRAL-in March 2025. We strictly included randomized controlled trials (RCTs) that compared patients who received SGLT2is to control patients regarding mortality outcomes. All-cause mortality up to one year, all-cause mortality more than one year, cardiovascular mortality, renal mortality and in-hospital mortality were the extracted outcomes. Finally, RevMan (5.4) was adopted for meta-analysis, and OpenMeta analyst software was adopted for meta-regression. Fifty clinical trials met the eligibility criteria of the current systematic review and meta-analysis. SGLT2 inhibitors significantly reduced all-cause mortality in studies with follow-up of up to one year (RR = 0.89, 95% CI [0.80-0.99], <i>p<\/i> = 0.03). This early survival benefit was primarily driven by the subgroup of patients treated during acute cardiac decompensation (RR = 0.76, 95% CI [0.60-0.97], <i>p<\/i> = 0.03). Furthermore, long-term follow-up beyond one year showed a significant reduction in all-cause mortality (RR = 0.89, 95% CI [0.85-0.94], <i>p<\/i> &lt; 0.0001), particularly among patients with chronic heart failure, chronic kidney disease (CKD), and diabetes mellitus (DM) with established cardiovascular disease (CVD) (following sensitivity analyses). Cardiovascular mortality was also significantly reduced overall (RR = 0.88, 95% CI [0.84-0.94], <i>p<\/i> &lt; 0.0001), with the greatest benefit observed in chronic heart failure and CKD subgroups. SGLT2 inhibitors as a class provide a consistent and significant reduction in all-cause mortality across both short-term (up to one year) and long-term follow-up. The early survival benefit is particularly evident when initiated during acute cardiac decompensation, while the long-term benefit extends to chronic heart failure, CKD, and high-risk DM. Future well-designed trials are needed to address the impact of less-explored SGLT2 inhibitors and understudied populations."]},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Movila","ForeName":"Dana Emilia","Initials":"DE","AffiliationInfo":[{"Affiliation":"University Clinic of Internal Medicine and Ambulatory Care, Prevention and Cardiovascular Recovery, Department VI-Cardiology, \"Victor Babes\" University of Medicine and Pharmacy, 300041 Timisoara, Romania."},{"Affiliation":"Research Centre of Timisoara Institute of Cardiovascular Diseases, \"Victor Babes\" University of Medicine and Pharmacy, 300041 Timisoara, Romania."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Motofelea","ForeName":"Alexandru Catalin","Initials":"AC","Identifier":[{"@attributes":{"Source":"ORCID"},"@text":"0000-0003-4297-077X"}],"AffiliationInfo":[{"Affiliation":"Centre for Molecular Research in Nephrology and Vascular Disease\/MOL-NEPHRO-VASC, \"Victor Babes\" University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Dragan","ForeName":"Simona Ruxanda","Initials":"SR","Identifier":[{"@attributes":{"Source":"ORCID"},"@text":"0000-0002-3892-0211"}],"AffiliationInfo":[{"Affiliation":"University Clinic of Internal Medicine and Ambulatory Care, Prevention and Cardiovascular Recovery, Department VI-Cardiology, \"Victor Babes\" University of Medicine and Pharmacy, 300041 Timisoara, Romania."},{"Affiliation":"Research Centre of Timisoara Institute of Cardiovascular Diseases, \"Victor Babes\" University of Medicine and Pharmacy, 300041 Timisoara, Romania."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Schiller","ForeName":"Adalbert","Initials":"A","AffiliationInfo":[{"Affiliation":"Centre for Molecular Research in Nephrology and Vascular Disease\/MOL-NEPHRO-VASC, \"Victor Babes\" University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Ionac","ForeName":"Adina","Initials":"A","AffiliationInfo":[{"Affiliation":"Department of Cardiology, \"Victor Babes\" University of Medicine and Pharmacy, 300041 Timisoara, Romania."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Motofelea","ForeName":"Nadica","Initials":"N","Identifier":[{"@attributes":{"Source":"ORCID"},"@text":"0009-0007-7597-823X"}],"AffiliationInfo":[{"Affiliation":"Department of Obstetrics and Gynecology, \"Victor Babes\" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Caruntu","ForeName":"Florina","Initials":"F","AffiliationInfo":[{"Affiliation":"First Department of Internal Medicine, Medical Semiology II, \"Victor Babes\" University of Medicine and Pharmacy, 300041 Timisoara, Romania."},{"Affiliation":"Multidisciplinary Heart Research Center, \"Victor Babes\" University of Medicine and Pharmacy, 300041 Timisoara, Romania."}]}]},"Language":["eng"],"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D016428"},"@text":"Journal Article"},{"@attributes":{"UI":"D000078182"},"@text":"Systematic Review"},{"@attributes":{"UI":"D017418"},"@text":"Meta-Analysis"},{"@attributes":{"UI":"D016454"},"@text":"Review"}]},"ArticleDate":[{"@attributes":{"DateType":"Electronic"},"Year":"2026","Month":"03","Day":"31"}]},"MedlineJournalInfo":{"Country":"Switzerland","MedlineTA":"Int J Mol Sci","NlmUniqueID":"101092791","ISSNLinking":"1422-0067"},"ChemicalList":{"Chemical":[{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D000077203"},"@text":"Sodium-Glucose Transporter 2 Inhibitors"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D006801","MajorTopicYN":"N"},"@text":"Humans"}},{"DescriptorName":{"@attributes":{"UI":"D000077203","MajorTopicYN":"Y"},"@text":"Sodium-Glucose Transporter 2 Inhibitors"},"QualifierName":[{"@attributes":{"UI":"Q000627","MajorTopicYN":"N"},"@text":"therapeutic use"}]},{"DescriptorName":{"@attributes":{"UI":"D003924","MajorTopicYN":"Y"},"@text":"Diabetes Mellitus, Type 2"},"QualifierName":[{"@attributes":{"UI":"Q000188","MajorTopicYN":"N"},"@text":"drug therapy"},{"@attributes":{"UI":"Q000401","MajorTopicYN":"N"},"@text":"mortality"}]},{"DescriptorName":{"@attributes":{"UI":"D002318","MajorTopicYN":"N"},"@text":"Cardiovascular Diseases"},"QualifierName":[{"@attributes":{"UI":"Q000401","MajorTopicYN":"N"},"@text":"mortality"},{"@attributes":{"UI":"Q000188","MajorTopicYN":"N"},"@text":"drug therapy"}]},{"DescriptorName":{"@attributes":{"UI":"D016032","MajorTopicYN":"N"},"@text":"Randomized Controlled Trials as Topic"}}]},"KeywordList":[{"@attributes":{"Owner":"NOTNLM"},"Keyword":[{"@attributes":{"MajorTopicYN":"N"},"@text":"SGLT2 inhibitor"},{"@attributes":{"MajorTopicYN":"N"},"@text":"all-cause mortality"},{"@attributes":{"MajorTopicYN":"N"},"@text":"cardiovascular mortality"},{"@attributes":{"MajorTopicYN":"N"},"@text":"death"}]}]},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"received"},"Year":"2026","Month":"2","Day":"5"},{"@attributes":{"PubStatus":"revised"},"Year":"2026","Month":"3","Day":"15"},{"@attributes":{"PubStatus":"accepted"},"Year":"2026","Month":"3","Day":"20"},{"@attributes":{"PubStatus":"medline"},"Year":"2026","Month":"4","Day":"14","Hour":"6","Minute":"32"},{"@attributes":{"PubStatus":"pubmed"},"Year":"2026","Month":"4","Day":"14","Hour":"6","Minute":"31"},{"@attributes":{"PubStatus":"entrez"},"Year":"2026","Month":"4","Day":"14","Hour":"1","Minute":"8"}]},"PublicationStatus":"epublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"41977354"},{"@attributes":{"IdType":"doi"},"@text":"10.3390\/ijms27073168"},{"@attributes":{"IdType":"pii"},"@text":"ijms27073168"}]}}}}