biostudies-literatureKnowler WCNIDDK NIH HHSNIA NIH HHSNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute on Aging1668-1675https://www.ebi.ac.uk/biostudies/studies/S-EPMC12451852biostudies-literatureUnknown48(10)The Diabetes Prevention Program (DPP) was a 3-year randomized clinical trial (RCT) with evaluation of lifestyle and metformin interventions compared with placebo for diabetes prevention in high-risk adults. Both interventions significantly reduced diabetes incidence, prompting the long-term Diabetes Prevention Program Outcomes Study (DPPOS) to assess the progression of diabetes and its complications over 22 years. During follow-up, departures from the original metformin or placebo assignment occurred primarily because of development of diabetes that, by protocol, was managed by clinicians outside the study, after participants developed diabetes with HbA1c ≥7.0%. Diabetes development led to changes in metformin treatment and addition of other glucose-lowering therapies. Using statistical meDiabetes careAnalysis of Long-term Follow-up of a Randomized Clinical Trial With Departures From Assigned Treatments: Estimation of Metformin Effects on Diabetes and Its Complications in the Diabetes Prevention Program Outcomes Study.PMC12451852U01 DK048404, U01 DK048387, U01 DK048407U01 DK048349, U01 DK048381, U01 DK048468U01 DK048407U01 DK048434, U01 DK048485, U01 DK048375U01 DK048349U01 DK048404U01 DK048406U01 DK048443U01 DK048411, U01 DK048406U01 DK048400U01 DK048489U01 DK048514, U01 DK048437, U01 DK048413U01 DK048468U01 DK048485U01 DK048387U01 DK048380U01 DK048381U01 DK048489, U01 DK048339, U01 DK0483775 U19 AG078558U01 DK048380, U01 DK048397, U01 DK048412U01 DK048437U01 DK048514U19 AG078558U01 DK048339U01 DK048377U01 DK048443, and U01 DK048400U01 DK048411U01 DK048412U01 DK048434U01 DK048413U01 DK048375U01 DK048397Caro JFLaferrere BTestaverde LHorse EHill Golden SKellum TSmith CFBoggs GJohnson MKBrancati FLPercy CAEnote ASmith CMKavena KShu SLeon LSewenemewa 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DEndres RKuo SWhittington TLee CPowell DMarcovina SPitts TPrice DWChu KKriska AAndon NRowse DHagamen SEastman RPolczynski EWernimont CArky RAMcPherson DHazuda HPAllen AO'Leary DSmith KGMichaels SNeira NWilson CReamer SGrimes KLActon KJLenz DSmith KAGibbs PRautaharju PHilbrich RLambert LBrown ASpandorfer JBenz WHadden AUtsey ERainville RBarber RSansoucy JBrown ERautaharju FNash PVDabelea DPassaro MThomas CCBondi KHensley SBudget MGarg RBouffard ALowe ARutledge LMKVan Wye GEHGillis BClark JMPark JIgnaut JMLuchsinger JAXapthalamous KHerman WHBoyle PJMorris LHStimpson CChavez MManly JPi-Sunyer FXStephens SDoughty MSBrandle MO'Neal KTseng BIsaac JVargo PSpellman JGonzales YMiddelbeek RJWWilliamson DQuitingon MWilliamson PCrandall JPBaker-Ladao NKBlodi BRaymond APEFrieson SLBavido-Arrage CIngraham LEAkbar KMcKitrick CKriska AMStich TKing CViolino EKennedy BMGadde KMBucca BGarimella PFoulkes MMorgan TAroda VWaters DBennett PHCampbell CJoseph HDias LMather KJJanicek RfalseAnalysis of Long-term Follow-up of a Randomized Clinical Trial With Departures From Assigned Treatments: Estimation of Metformin Effects on Diabetes and Its Complications in the Diabetes Prevention Program Outcomes Study.The Diabetes Prevention Program (DPP) was a 3-year randomized clinical trial (RCT) with evaluation of lifestyle and metformin interventions compared with placebo for diabetes prevention in high-risk adults. Both interventions significantly reduced diabetes incidence, prompting the long-term Diabetes Prevention Program Outcomes Study (DPPOS) to assess the progression of diabetes and its complications over 22 years. During follow-up, departures from the original metformin or placebo assignment occurred primarily because of development of diabetes that, by protocol, was managed by clinicians outside the study, after participants developed diabetes with HbA1c ≥7.0%. Diabetes development led to changes in metformin treatment and addition of other glucose-lowering therapies. Using statistical me2025-01-01T00:00:00Z2025 Oct2026-04-30T03:20:43.007Z2026-04-30T03:12:08.556ZS-EPMC124518524085717510.2337/dci25-0032