Evaluate Side Effects of Sglt-2 Inhibitors in Extreme Elderly Outpatients: Real-world Evidence From a Low- and Middle-income Country

Evaluate Side Effects of Sglt-2 Inhibitors in Extreme Elderly Outpatients: Real-world Evidence From a Low- and Middle-income Country | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluate Side Effects of Sglt-2 Inhibitors in Extreme Elderly Outpatients: Real-world Evidence From a Low- and Middle-income Country Van Hoang, Danh Nguyen Hien Duong, Quoc Thang Le, Thi Viet Nga Nguyen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9142235/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Very elderly patients are increasingly represented in clinical practice but remain underrepresented in randomized trials evaluating sodium–glucose cotransporter-2 inhibitors (SGLT2i). Although these agents have demonstrated substantial cardiovascular and renal benefits in heart failure (HF) and type 2 diabetes mellitus (T2DM), concerns regarding safety and tolerability. Evidence is particularly limited in low- and middle-income countries (LMICs), where socioeconomic and healthcare factors may influence treatment persistence. This study aimed to evaluate the safety profile, adverse events, and treatment discontinuation of SGLT2 inhibitors in very elderly outpatients. Methods: We conducted a retrospective observational study at the outpatient clinics of Hanoi Heart Hospital, Vietnam, between May 2023 and July 2024. Patients aged ≥ 85 years with HF or T2DM receiving SGLT2 inhibitors were included. Baseline demographic, clinical, laboratory, and medication data were collected. The primary outcome was severe adverse events leading to permanent discontinuation of SGLT2 inhibitor therapy. Secondary outcomes included non-severe adverse events, hospital readmission within one year, and mortality. Clinical outcomes were analyzed descriptively and stratified by age group (< 90 vs ≥ 90 years). Results A total of 316 patients were included (mean age 87.98 ± 3.09 years; 57.6% female). Heart failure was present in 94.0% of the cohort, with a median left ventricular ejection fraction of 50% (IQR 40–62). Major comorbidities included ischemic heart disease (70.9%), hypertension (62.3%), diabetes mellitus (43.4%), and chronic kidney disease (34.8%). Over one year of follow-up, SGLT2 inhibitor therapy was discontinued in 34.2% of patients. The most common causes of discontinuation were economic constraints (21.9%), acute kidney injury (11.4%), and death (12.4%). Notably, patients aged ≥ 90 years experienced substantially higher discontinuation due to acute kidney injury (25.0%) and death (33.3%) compared with those aged < 90 years. The one-year readmission rate was 11.7%, and overall mortality was 4.1%. Conclusions In this real-world cohort of very elderly outpatients, SGLT2 inhibitors demonstrated an acceptable safety profile but were associated with a relatively high treatment discontinuation rate. Clinical adverse events, particularly acute kidney injury, were more frequent among patients aged ≥ 90 years, while economic factors substantially influenced treatment persistence. These findings highlight the importance of individualized risk assessment, close monitoring, and consideration of socioeconomic barriers when prescribing SGLT2 inhibitors in very elderly populations in LMIC settings. Clinical trial registration Not applicable. Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9142235","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":617037919,"identity":"0cf1691d-834e-4230-a954-cd19193fa060","order_by":0,"name":"Van Hoang","email":"","orcid":"","institution":"Ha Noi Heart Hospital","correspondingAuthor":false,"prefix":"","firstName":"Van","middleName":"","lastName":"Hoang","suffix":""},{"id":617037920,"identity":"2cd55cc1-aec4-4d92-ab47-7e9defdbd60c","order_by":1,"name":"Danh Nguyen Hien Duong","email":"","orcid":"","institution":"VinUniversity","correspondingAuthor":false,"prefix":"","firstName":"Danh","middleName":"Nguyen Hien","lastName":"Duong","suffix":""},{"id":617037923,"identity":"467da254-53bf-48d4-8455-4d17d9acd1af","order_by":2,"name":"Quoc Thang Le","email":"","orcid":"","institution":"VinUniversity","correspondingAuthor":false,"prefix":"","firstName":"Quoc","middleName":"Thang","lastName":"Le","suffix":""},{"id":617037924,"identity":"29e1286d-87f6-4e78-8862-17741a85b4e7","order_by":3,"name":"Thi Viet Nga Nguyen","email":"","orcid":"","institution":"Ha Noi Heart Hospital","correspondingAuthor":false,"prefix":"","firstName":"Thi","middleName":"Viet Nga","lastName":"Nguyen","suffix":""},{"id":617037926,"identity":"8882c8da-563f-433f-bb4b-0917140e241f","order_by":4,"name":"Thanh Hoa Tran","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYLACxgYGBgMJIOMDgwSDAUgkAY9qHhBxEKqFcUYCqVqYeYBKDQi5yV768LPHH3fY5ZlLNx/8bPvDItqc/ezBBw8YDufhtIUvzdzg4JnkYss5x5KlcxIkcnf25CUbJDAcLsaphYfBTOJgG3Pihhs5BmAtGw7kmEkkMKQlNuDUwv4NqKUepMX4twVIy/k3hLTwgGw5DNJiJs0A0nIDbIsNbi1neMokzrYdB2pJS7PsSQNpeWNskGCAWwt7D/s2icq2aqCW5MM3ftjUAR2WY/jwR4UETi24AMHYGQWjYBSMglGADwAA+uBaw8OPzJsAAAAASUVORK5CYII=","orcid":"","institution":"Ha Noi Heart Hospital","correspondingAuthor":true,"prefix":"","firstName":"Thanh","middleName":"Hoa","lastName":"Tran","suffix":""}],"badges":[],"createdAt":"2026-03-16 23:23:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9142235/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9142235/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109296617,"identity":"60039394-f2ca-46d6-9e7b-dfd3ac570262","added_by":"auto","created_at":"2026-05-15 08:48:34","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":532260,"visible":true,"origin":"","legend":"","description":"","filename":"EVALUATESIDEEFFECTSOFSGLT2iINEXTREMEELDERLYOUTPATIENTSREALWORLDEVIDENCEFROMALMIC.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9142235/v1_covered_f5007972-6987-4df1-9416-ccc673321f8c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eEvaluate Side Effects of Sglt-2 Inhibitors in Extreme Elderly Outpatients: Real-world Evidence From a Low- and Middle-income Country\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9142235/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9142235/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eVery elderly patients are increasingly represented in clinical practice but remain underrepresented in randomized trials evaluating sodium\u0026ndash;glucose cotransporter-2 inhibitors (SGLT2i). Although these agents have demonstrated substantial cardiovascular and renal benefits in heart failure (HF) and type 2 diabetes mellitus (T2DM), concerns regarding safety and tolerability. Evidence is particularly limited in low- and middle-income countries (LMICs), where socioeconomic and healthcare factors may influence treatment persistence. This study aimed to evaluate the safety profile, adverse events, and treatment discontinuation of SGLT2 inhibitors in very elderly outpatients.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective observational study at the outpatient clinics of Hanoi Heart Hospital, Vietnam, between May 2023 and July 2024. Patients aged\u0026thinsp;\u0026ge;\u0026thinsp;85 years with HF or T2DM receiving SGLT2 inhibitors were included. Baseline demographic, clinical, laboratory, and medication data were collected. The primary outcome was severe adverse events leading to permanent discontinuation of SGLT2 inhibitor therapy. Secondary outcomes included non-severe adverse events, hospital readmission within one year, and mortality. Clinical outcomes were analyzed descriptively and stratified by age group (\u0026lt;\u0026thinsp;90 vs\u0026thinsp;\u0026ge;\u0026thinsp;90 years).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 316 patients were included (mean age 87.98\u0026thinsp;\u0026plusmn;\u0026thinsp;3.09 years; 57.6% female). Heart failure was present in 94.0% of the cohort, with a median left ventricular ejection fraction of 50% (IQR 40\u0026ndash;62). Major comorbidities included ischemic heart disease (70.9%), hypertension (62.3%), diabetes mellitus (43.4%), and chronic kidney disease (34.8%). Over one year of follow-up, SGLT2 inhibitor therapy was discontinued in 34.2% of patients. The most common causes of discontinuation were economic constraints (21.9%), acute kidney injury (11.4%), and death (12.4%). Notably, patients aged\u0026thinsp;\u0026ge;\u0026thinsp;90 years experienced substantially higher discontinuation due to acute kidney injury (25.0%) and death (33.3%) compared with those aged\u0026thinsp;\u0026lt;\u0026thinsp;90 years. The one-year readmission rate was 11.7%, and overall mortality was 4.1%.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn this real-world cohort of very elderly outpatients, SGLT2 inhibitors demonstrated an acceptable safety profile but were associated with a relatively high treatment discontinuation rate. Clinical adverse events, particularly acute kidney injury, were more frequent among patients aged\u0026thinsp;\u0026ge;\u0026thinsp;90 years, while economic factors substantially influenced treatment persistence. These findings highlight the importance of individualized risk assessment, close monitoring, and consideration of socioeconomic barriers when prescribing SGLT2 inhibitors in very elderly populations in LMIC settings.\u003c/p\u003e\u003ch2\u003eClinical trial registration\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e","manuscriptTitle":"Evaluate Side Effects of Sglt-2 Inhibitors in Extreme Elderly Outpatients: Real-world Evidence From a Low- and Middle-income Country","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-09 20:43:12","doi":"10.21203/rs.3.rs-9142235/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"82995180-f627-477c-83b4-0627da689519","owner":[],"postedDate":"April 9th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-15T07:09:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-13T01:57:28+00:00","index":47,"fulltext":""},{"type":"reviewerAgreed","content":"159639585657481366384449007507000829431","date":"2026-05-04T06:28:43+00:00","index":46,"fulltext":""},{"type":"reviewerAgreed","content":"105920259839252010129083612864963164389","date":"2026-05-04T00:00:17+00:00","index":45,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-03T03:59:20+00:00","index":43,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T07:25:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-09 20:43:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9142235","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9142235","identity":"rs-9142235","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}