biostudies-literatureFelton JLLeona M. and Harry B. Helmsley Charitable TrustNIDDK NIH HHSNIAID NIH HHSMedical Research CouncilJuvenile Diabetes Research Foundation US Department of Veteran Affairs The Ball Brothers Foundation George and Frances Ball Foundation Doris Duke Charitable Foundation John Templeton FoundationDiabetes UKAmerican Diabetes AssociationNovo Nordisk FondenU.S. Department of Health &amp; Human Services | National Institutes of Health130https://www.ebi.ac.uk/biostudies/studies/S-EPMC10550983biostudies-literatureUnknown3(1)<h4>Background</h4>Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification.<h4>Methods</h4>To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument.<h4>Results</h4>We identify and summarize 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss at disease onset. Seventeen interventions, mostly immunotherapies, show benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employ precision analyses to assess features linked to treatment response. Age, beta cell function measures, and immune phenotypes are most frequently tested. However, analyses are typically not prespecified, with inconsistent methods of reporting, and tend to report positive findings.<h4>Conclusions</h4>While the quality of prevention and intervention trials is overall high, the low quality of precision analyses makes it difficult to draw meaningful conclusions that inform clinical practice. To facilitate precision medicine approaches to T1D prevention, considerations for future precision studies include the incorporation of uniform outcome measures, reproducible biomarkers, and prespecified, fully powered precision analyses into future trial design.Communications medicineDisease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review.PMC10550983R01 AI141952R01 DK12184316/0005529MC_UU_00014/4Merino JTaylor RNolan JJAuh SFernandez-Balsells MMSarkar SEckel RHHabibi NGaillard RThuesen ACBKoivula RWJain RPowe CEUrazbayeva MGottlieb PAHannah WEvans-Molina CPankow JSNakabuye MSemnani-Azad ZYoung KMathieu CTye SCTuomi TMassey RZhu YYu GLoos RJFGillard PMclennan NMLong SASelvin EBodhini DSevilla-Gonzalez MSherifali DPratley REJacobsen LMPazmino SADA/EASD PMDIKettunen JLTClark ALPilla SJMekonnen EGGriffin KRedman LMGingras VStefan NSemple RKMonaco GSFRich SSSweeting ARaghavan SFrancis ECGomez MFSteenackers NSvalastoga PLim LLSaint-Martin COram RChen MMannisto JMEBeltrand JSims EKJones AGDeutsch AJBoyle KHood KKWagner RIsmail HMGoodarzi MOYamamoto JMSaeed ZMost JLiu KRooney MRSpeake CVesco KKSherr JLJosefson JLPerez DAukrust ILeung GKWVatier CMorieri MLDennis JMMorton RWMurphy RGitelman SEKreienkamp RJPhilipson LHHaider EOwen KRPerng WWong JJMiller RGHansen TDickens LTZhang YPolak MZhou SJRedondo MJProvenzano MFlorez JCAmouyal CScholtens DMRied-Larsen MGriffin KJMolnes JSteck AKSheu WHBenham JLMa RCWGitelman SIkle JMLibman IMSanthakumar VWhite SLZhang CDiMeglio LARay DNjolstad PRGrieger JAHughes AHivert MFVilsboll TCorcoy RReynolds RMAndersen MKFelton JLHattersley ATHarris-Kawano ABrown RJFranks PWTosur MDudenhoffer-Pfeifer MPrystupa KMeigs JBHoag Bde Franco EPetrie JRGreeley SAWGruber CKahkoska ARClemmensen CCheng FCostacou TColclough KChivers SCUkke GGFlanagan SEWallace ASChikowore TMotala AAOzanne SEWang CCde Souza RPatel KAOzkan BHuang CFawcett AJLaffel LMWentworth JMOnengut-Gumuscu SDabelea DAhmad ALeong AGloyn ALFitipaldi HMohan VAiken COram RAMathioudakis NTobias DKBonham MPJohnson RKNaylor RNStoy JMisra SLim SSPollin TIUdler MSMcGovern ADawed AYSchon MMixter EKanbour SBillings LKHirsch IBPearson ERMaloney KATakele WWLowe WLPathirana MCromer SJTam CHGuasch-Ferre MVan der Schueren BPop-Busui RDuan DPomares-Millan HFitzpatrick SLKwak SHQuinteros AStanislawski MAfalseDisease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review.<h4>Background</h4>Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification.<h4>Methods</h4>To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument.<h4>Results</h4>We identify and summarize 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss at disease onset. Seventeen interventions, mostly immunotherapies, show benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employ precision analyses to assess features linked to treatment response. Age, beta cell function measures, and immune phenotypes are most frequently tested. However, analyses are typically not prespecified, with inconsistent methods of reporting, and tend to report positive findings.<h4>Conclusions</h4>While the quality of prevention and intervention trials is overall high, the low quality of precision analyses makes it difficult to draw meaningful conclusions that inform clinical practice. To facilitate precision medicine approaches to T1D prevention, considerations for future precision studies include the incorporation of uniform outcome measures, reproducible biomarkers, and prespecified, fully powered precision analyses into future trial design.2023-01-01T00:00:00Z2023 Oct2025-04-22T06:54:15.487Z2025-02-19T01:37:25.811ZS-EPMC105509833779416910.1038/s43856-023-00357-y