Meta-analysis of the effect of metformin on the regression of different types of prediabetes mellitus

Meta-analysis of the effect of metformin on the regression of different types of prediabetes mellitus | 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 Meta-analysis of the effect of metformin on the regression of different types of prediabetes mellitus 夏 钱, 必应 王, Xiaohong Yang, Bo Qian, Yali Hu, Qun Zhang, Junjun Guo, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6620890/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 OBJECTIVE To investigate the differences in the efficacy of metformin interventions for progression to type 2 diabetes in people with different subtypes of prediabetes (impaired fasting glucose, impaired glucose tolerance, mixed). MATERIALS AND METHODS Following the PRISMA guidelines, ten Chinese and English databases including PubMed and Cochrane were systematically searched (up to May 2025), and 18 randomized controlled trials were included in a meta-analysis using randomized/fixed-effects models to assess the effect of metformin versus lifestyle/placebo interventions on the incidence of type 2 diabetes, and to calculate the risk ratios (RR) and their 95% confidence intervals (CI), and subgroup analyses were performed based on prediabetes subtype and length of intervention. All statistical analyses were performed using Review Manager 5.4 software. RESULTS Eighteen RCTs were included and found a 35% lower risk of T2DM onset in the metformin group compared with the control group, compared with lifestyle change/placebo (RR = 0.65, 95% CI [0.55, 0.77], P < 0.00001), but there was moderate heterogeneity. Subgroup analysis of participants with different subtypes of prediabetes showed a 62% risk reduction (RR = 0.38, 95% CI [0.38, 0.61], P < 0.0001) for the IFG subtype with the best effect, and a 42% risk reduction (RR = 0.58, 95% CI [0.43, 0.79], P < 0.0004) for the IGT subtype; Mixed risk reduction was 23% (RR = 0.77, 95% CI [0.70, 0.86], P < 0.00001). In addition, intervention duration ≤ 24 months had a more significant effect on the IGT subtype (RR = 0.22, P < 0.0001); a higher proportion of the glycemic inverse metformin group returned to normoglycemia than the control group (RR = 1.80, 95% CI [1.39, 2.34], P < 0.0001). CONCLUSION Metformin can effectively delay the progression of prediabetes to type 2 diabetes, and the intervention effect on IFG subtypes was significantly better than that of IGT and mixed types, which may be related to the mechanism of drug targeting hepatic gluconeogenesis. It is recommended that combined metformin treatment be prioritized for the IFG population. prediabetes type 2 diabetes metformin meta-analysis 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-6620890","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":457128306,"identity":"2f5af5c5-2185-45d1-adc6-1e1ef962a89a","order_by":0,"name":"夏 钱","email":"","orcid":"","institution":"Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"夏","middleName":"","lastName":"钱","suffix":""},{"id":457128307,"identity":"93c3d22b-3b71-4e30-a239-44be57c80aff","order_by":1,"name":"必应 王","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYBACNmbmAwc+VDAwG4B4PMRo4WdvS3w44wwpWiR7zhgb87YxMBCvxeBGjpk077w6dnOJBMYHb9sY5M0Ja0krk5y7jY3ZckYCs+HcNgbDnQ0EtSRvk3i7jYfZ4EYCmzTQhQkGBwhqSTCT4J0jAdLC/psoLZI9R4wNeRsMwLYwE6UFEsjHEpgNzjxslpxzTsJwAyEtkKisqUs2OJ588MObMht5grbAQDIDA2MDkJYgUj0Q2BGvdBSMglEwCkYcAABTZj750kGWRQAAAABJRU5ErkJggg==","orcid":"","institution":"Key Laboratory of Precise Prevention and Control of Major Chronic Diseases","correspondingAuthor":true,"prefix":"","firstName":"必应","middleName":"","lastName":"王","suffix":""},{"id":457128308,"identity":"5d16fa9c-a69c-434b-b5ba-ae538d52f149","order_by":2,"name":"Xiaohong Yang","email":"","orcid":"","institution":"Huzhou 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Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Qun","middleName":"","lastName":"Zhang","suffix":""},{"id":457128312,"identity":"786261b8-2dcf-4914-9c9c-a0f6d265c4b7","order_by":6,"name":"Junjun Guo","email":"","orcid":"","institution":"Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Junjun","middleName":"","lastName":"Guo","suffix":""},{"id":457128313,"identity":"bab64fc4-288b-4b23-9f14-6dec84ae09b2","order_by":7,"name":"Guanzhen Jia","email":"","orcid":"","institution":"Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Guanzhen","middleName":"","lastName":"Jia","suffix":""}],"badges":[],"createdAt":"2025-05-08 12:53:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6620890/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6620890/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82907075,"identity":"1c1d9a35-f330-4424-8450-960cf88b659c","added_by":"auto","created_at":"2025-05-16 14:31:24","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":792222,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6620890/v1_covered_6d6955fa-d89f-441c-af97-f5e5dcb185c2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Meta-analysis of the effect of metformin on the regression of different types of prediabetes mellitus","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":"prediabetes, type 2 diabetes, metformin, meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-6620890/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6620890/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eOBJECTIVE\u003c/h2\u003e \u003cp\u003eTo investigate the differences in the efficacy of metformin interventions for progression to type 2 diabetes in people with different subtypes of prediabetes (impaired fasting glucose, impaired glucose tolerance, mixed).\u003c/p\u003e\u003ch2\u003eMATERIALS AND METHODS\u003c/h2\u003e \u003cp\u003eFollowing the PRISMA guidelines, ten Chinese and English databases including PubMed and Cochrane were systematically searched (up to May 2025), and 18 randomized controlled trials were included in a meta-analysis using randomized/fixed-effects models to assess the effect of metformin versus lifestyle/placebo interventions on the incidence of type 2 diabetes, and to calculate the risk ratios (RR) and their 95% confidence intervals (CI), and subgroup analyses were performed based on prediabetes subtype and length of intervention. All statistical analyses were performed using Review Manager 5.4 software.\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003eEighteen RCTs were included and found a 35% lower risk of T2DM onset in the metformin group compared with the control group, compared with lifestyle change/placebo (RR\u0026thinsp;=\u0026thinsp;0.65, 95% CI [0.55, 0.77], P\u0026thinsp;\u0026lt;\u0026thinsp;0.00001), but there was moderate heterogeneity. Subgroup analysis of participants with different subtypes of prediabetes showed a 62% risk reduction (RR\u0026thinsp;=\u0026thinsp;0.38, 95% CI [0.38, 0.61], P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) for the IFG subtype with the best effect, and a 42% risk reduction (RR\u0026thinsp;=\u0026thinsp;0.58, 95% CI [0.43, 0.79], P\u0026thinsp;\u0026lt;\u0026thinsp;0.0004) for the IGT subtype; Mixed risk reduction was 23% (RR\u0026thinsp;=\u0026thinsp;0.77, 95% CI [0.70, 0.86], P\u0026thinsp;\u0026lt;\u0026thinsp;0.00001). In addition, intervention duration\u0026thinsp;\u0026le;\u0026thinsp;24 months had a more significant effect on the IGT subtype (RR\u0026thinsp;=\u0026thinsp;0.22, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001); a higher proportion of the glycemic inverse metformin group returned to normoglycemia than the control group (RR\u0026thinsp;=\u0026thinsp;1.80, 95% CI [1.39, 2.34], P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e\u003ch2\u003eCONCLUSION\u003c/h2\u003e \u003cp\u003eMetformin can effectively delay the progression of prediabetes to type 2 diabetes, and the intervention effect on IFG subtypes was significantly better than that of IGT and mixed types, which may be related to the mechanism of drug targeting hepatic gluconeogenesis. It is recommended that combined metformin treatment be prioritized for the IFG population.\u003c/p\u003e","manuscriptTitle":"Meta-analysis of the effect of metformin on the regression of different types of prediabetes mellitus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-16 10:03:37","doi":"10.21203/rs.3.rs-6620890/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":"87e0f144-c9b3-4091-a868-01b02b4f3878","owner":[],"postedDate":"May 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-18T11:30:30+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-16 10:03:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6620890","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6620890","identity":"rs-6620890","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}