Vitamin D Supplementation Improves Glycemic Control, Inflammation, and Lipid Profile in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Vitamin D Supplementation Improves Glycemic Control, Inflammation, and Lipid Profile in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials | 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 Systematic Review Vitamin D Supplementation Improves Glycemic Control, Inflammation, and Lipid Profile in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Madhubala M, Harish AU This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9394957/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: Vitamin D deficiency has been increasingly associated with the pathogenesis of type 2 diabetes mellitus (T2DM), influencing insulin resistance, β-cell function, inflammation, and cardiovascular risk. However, evidence from randomized controlled trials (RCTs) remains inconsistent. Objective: To systematically evaluate the effect of vitamin D supplementation on glycemic control, insulin resistance, inflammatory markers, and lipid profile in individuals with T2DM. Methods: A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA 2020 guidelines. PubMed, Scopus, and Embase were searched from 2010 to 2026. Eighteen RCTs involving approximately 2,000 participants were included. A random-effects model (DerSimonian–Laird) was used to calculate pooled mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Subgroup analyses were performed based on geographic region, study population, and sample size. Sensitivity analysis using a leave-one-out approach and GRADE assessment were conducted to evaluate robustness and certainty of evidence. Results: Vitamin D supplementation significantly improved multiple metabolic outcomes, including HbA1c (MD = −0.42%, 95% CI: −0.32 to −0.16; I² = 27%), fasting blood glucose (MD = −9.5 mg/dL; I² = 16%), and HOMA-IR (MD = −0.98; I² = 60%). Significant reductions were also observed in C-reactive protein (MD = −0.46 mg/L; I² = 30%), low-density lipoprotein cholesterol (MD = −5.85 mg/dL; I² = 22%), and triglycerides (MD = −6.51 mg/dL; I² = 0%). Subgroup analysis demonstrated greater effects in Asian populations. Sensitivity analysis confirmed the stability of results, and GRADE assessment indicated moderate to high certainty of evidence. Conclusion: Vitamin D supplementation is associated with modest but significant improvements in glycemic control, inflammation, and lipid parameters in individuals with T2DM. These findings support its role as a potential adjunct in metabolic management, particularly among vitamin D–deficient populations. Applied Biochemistry Vitamin D Type 2 Diabetes Mellitus HbA1c Insulin Resistance Meta-analysis Inflammation Lipid Profile Full Text Additional Declarations The authors declare no competing interests. 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-9394957","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":621714465,"identity":"7315f2e5-3a1c-4568-9449-26073e890b00","order_by":0,"name":"Madhubala M","email":"data:image/png;base64,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","orcid":"","institution":"All india instituite of medical sciences ,New Delhi","correspondingAuthor":true,"prefix":"","firstName":"Madhubala","middleName":"","lastName":"M","suffix":""},{"id":621714466,"identity":"e5c52c17-180c-4bb5-b574-836e14e43da7","order_by":1,"name":"Harish AU","email":"","orcid":"","institution":"SKIMS ,Soura","correspondingAuthor":false,"prefix":"","firstName":"Harish","middleName":"","lastName":"AU","suffix":""}],"badges":[],"createdAt":"2026-04-12 14:30:36","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9394957/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9394957/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106960344,"identity":"00527235-a8a9-400f-8e9c-c0ebd5b173da","added_by":"auto","created_at":"2026-04-15 09:20:21","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":456479,"visible":true,"origin":"","legend":"","description":"","filename":"systematicreviewrctSTUDY.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9394957/v1_covered_fe5949d6-8934-45f7-9666-2778ccfacdd3.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eVitamin D Supplementation Improves Glycemic Control, Inflammation, and Lipid Profile in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Vitamin D, Type 2 Diabetes Mellitus, HbA1c, Insulin Resistance, Meta-analysis, Inflammation, Lipid Profile","lastPublishedDoi":"10.21203/rs.3.rs-9394957/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9394957/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003cbr\u003e\nVitamin D deficiency has been increasingly associated with the pathogenesis of type 2 diabetes mellitus (T2DM), influencing insulin resistance, β-cell function, inflammation, and cardiovascular risk. However, evidence from randomized controlled trials (RCTs) remains inconsistent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e\u003cbr\u003e\nTo systematically evaluate the effect of vitamin D supplementation on glycemic control, insulin resistance, inflammatory markers, and lipid profile in individuals with T2DM.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003cbr\u003e\nA systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA 2020 guidelines. PubMed, Scopus, and Embase were searched from 2010 to 2026. Eighteen RCTs involving approximately 2,000 participants were included. A random-effects model (DerSimonian–Laird) was used to calculate pooled mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Subgroup analyses were performed based on geographic region, study population, and sample size. Sensitivity analysis using a leave-one-out approach and GRADE assessment were conducted to evaluate robustness and certainty of evidence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003cbr\u003e\nVitamin D supplementation significantly improved multiple metabolic outcomes, including HbA1c (MD = −0.42%, 95% CI: −0.32 to −0.16; I² = 27%), fasting blood glucose (MD = −9.5 mg/dL; I² = 16%), and HOMA-IR (MD = −0.98; I² = 60%). Significant reductions were also observed in C-reactive protein (MD = −0.46 mg/L; I² = 30%), low-density lipoprotein cholesterol (MD = −5.85 mg/dL; I² = 22%), and triglycerides (MD = −6.51 mg/dL; I² = 0%). Subgroup analysis demonstrated greater effects in Asian populations. Sensitivity analysis confirmed the stability of results, and GRADE assessment indicated moderate to high certainty of evidence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003cbr\u003e\nVitamin D supplementation is \u003cstrong\u003eassociated with modest but significant improvements\u003c/strong\u003e in glycemic control, inflammation, and lipid parameters in individuals with T2DM. These findings support its role as a potential adjunct in metabolic management, particularly among vitamin D–deficient populations.\u003c/p\u003e","manuscriptTitle":"Vitamin D Supplementation Improves Glycemic Control, Inflammation, and Lipid Profile in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-14 08:35:26","doi":"10.21203/rs.3.rs-9394957/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":"966ea96c-fa18-4a98-a3a3-51e3d09550dd","owner":[],"postedDate":"April 14th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":66159564,"name":"Applied Biochemistry"}],"tags":[],"updatedAt":"2026-04-14T08:35:26+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-14 08:35:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9394957","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9394957","identity":"rs-9394957","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}