{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:44:53Z","timestamp":1792291493134,"version":"4.4.0"},"reference-count":48,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Intern Med"],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:sec id=\"ab-ioi230100-4\"><jats:title>Importance<\/jats:title><jats:p>Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi230100-5\"><jats:title>Objective<\/jats:title><jats:p>To investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D).<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi230100-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi230100-7\"><jats:title>Exposures<\/jats:title><jats:p>Receiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi230100-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi230100-9\"><jats:title>Results<\/jats:title><jats:p>In total, 80\u202f178 patients (mean [SD] age, 58.5 [11.9] years; 43\u202f007 [53.6%] male) were followed up for 219\u202f941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi230100-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>The results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamainternmed.2023.8029","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T16:01:51Z","timestamp":1707753711000},"page":"375","source":"Crossref","is-referenced-by-count":96,"title":["Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease"],"prefix":"10.1001","volume":"184","author":[{"given":"Heejoon","family":"Jang","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hyeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sae Kyung","family":"Joo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Kyung","family":"Koo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woojoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"4","key":"ioi230100r1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention.","volume":"18","author":"Huang","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"12","key":"ioi230100r2","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1001\/jama.2020.2298","article-title":"Nonalcoholic steatohepatitis: a review.","volume":"323","author":"Sheka","year":"2020","journal-title":"JAMA"},{"issue":"9","key":"ioi230100r3","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1111\/liv.v39.9","article-title":"Nonalcoholic steatohepatitis is associated with a higher risk of advanced colorectal neoplasm.","volume":"39","author":"Cho","year":"2019","journal-title":"Liver Int"},{"issue":"9","key":"ioi230100r4","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/s41575-021-00448-y","article-title":"The complex link between NAFLD and type 2 diabetes mellitus\u2014mechanisms and treatments.","volume":"18","author":"Targher","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"4","key":"ioi230100r5","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.jhep.2019.06.021","article-title":"The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis.","volume":"71","author":"Younossi","year":"2019","journal-title":"J Hepatol"},{"issue":"9","key":"ioi230100r6","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/S2468-1253(23)00157-7","article-title":"Type 2 diabetes, hepatic decompensation, and hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: an individual participant-level data meta-analysis.","volume":"8","author":"Huang","year":"2023","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"1","key":"ioi230100r7","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.dld.2020.08.021","article-title":"Antidiabetic drugs and non-alcoholic fatty liver disease: a systematic review, meta-analysis and evidence map.","volume":"53","author":"Kumar","year":"2021","journal-title":"Dig Liver Dis"},{"key":"ioi230100r8","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102292","article-title":"Metabolic dysfunction-associated steatotic liver disease increases the risk of incident cardiovascular disease: a nationwide cohort study.","author":"Moon","year":"2023","journal-title":"eClinicalMedicine"},{"issue":"12","key":"ioi230100r9","doi-asserted-by":"publisher","first-page":"6163","DOI":"10.7314\/APJCP.2012.13.12.6163","article-title":"A comparison of the cancer incidence rates between the national cancer registry and insurance claims data in Korea.","volume":"13","author":"Seo","year":"2012","journal-title":"Asian Pac J Cancer Prev"},{"key":"ioi230100r10","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1471-230X-6-33","article-title":"The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population.","volume":"6","author":"Bedogni","year":"2006","journal-title":"BMC Gastroenterol"},{"issue":"1","key":"ioi230100r11","first-page":"30","article-title":"Medication adherence: the elephant in the room.","volume":"43","author":"Kim","year":"2018","journal-title":"US Pharm"},{"issue":"1","key":"ioi230100r12","doi-asserted-by":"publisher","first-page":"13","DOI":"10.24304\/kjcp.2022.32.1.13","article-title":"Use of SGLT2 inhibitor\/metformin fixed dose combination in Korea.","volume":"32","author":"Choi","year":"2022","journal-title":"Korean J Clin Pharm"},{"key":"ioi230100r13","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jclinepi.2016.04.014","article-title":"Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses.","volume":"79","author":"Hern\u00e1n","year":"2016","journal-title":"J Clin Epidemiol"},{"issue":"38","key":"ioi230100r14","doi-asserted-by":"publisher","first-page":"4574","DOI":"10.2174\/1381612825666190117102111","article-title":"Diagnosis of non-alcoholic fatty liver disease (NAFLD): current concepts.","volume":"24","author":"Papatheodoridi","year":"2018","journal-title":"Curr Pharm Des"},{"issue":"3","key":"ioi230100r15","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3350\/cmh.2021.0178","article-title":"KASL clinical practice guidelines: management of nonalcoholic fatty liver disease.","volume":"27","author":"Kang","year":"2021","journal-title":"Clin Mol Hepatol"},{"key":"ioi230100r16","doi-asserted-by":"publisher","first-page":"S103","DOI":"10.3350\/cmh.2022.0336","article-title":"Screening strategy for non-alcoholic fatty liver disease.","volume":"29","author":"Zhang","year":"2023","journal-title":"Clin Mol Hepatol"},{"issue":"28","key":"ioi230100r17","doi-asserted-by":"publisher","first-page":"3661","DOI":"10.1002\/sim.v34.28","article-title":"Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies.","volume":"34","author":"Austin","year":"2015","journal-title":"Stat Med"},{"issue":"3","key":"ioi230100r18","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1111\/biom.2000.56.issue-3","article-title":"Correcting for noncompliance and dependent censoring in an AIDS clinical trial with inverse probability of censoring weighted (IPCW) log-rank tests.","volume":"56","author":"Robins","year":"2000","journal-title":"Biometrics"},{"issue":"446","key":"ioi230100r19","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1080\/01621459.1999.10474144","article-title":"A proportional hazards model for the subdistribution of a competing risk.","volume":"94","author":"Fine","year":"1999","journal-title":"J Am Stat Assoc"},{"key":"ioi230100r20","doi-asserted-by":"publisher","first-page":"203","DOI":"10.2147\/CLEP","article-title":"Comparison of Charlson comorbidity index with SAPS and APACHE scores for prediction of mortality following intensive care.","volume":"3","author":"Christensen","year":"2011","journal-title":"Clin Epidemiol"},{"issue":"3","key":"ioi230100r21","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/81.3.515","article-title":"Proportional hazards tests and diagnostics based on weighted residuals.","volume":"81","author":"Grambsch","year":"1994","journal-title":"Biometrika"},{"issue":"4","key":"ioi230100r22","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1002\/hep.30626","article-title":"Sex differences in nonalcoholic fatty liver disease: state of the art and identification of research gaps.","volume":"70","author":"Lonardo","year":"2019","journal-title":"Hepatology"},{"issue":"3","key":"ioi230100r23","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1002\/bimj.v62.3","article-title":"Time-dependent mediators in survival analysis: modeling direct and indirect effects with the additive hazards model.","volume":"62","author":"Aalen","year":"2020","journal-title":"Biom J"},{"issue":"10","key":"ioi230100r24","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.2337\/dc17-0518","article-title":"Comparison of ipragliflozin and pioglitazone effects on nonalcoholic fatty liver disease in patients with type 2 diabetes: a randomized, 24-week, open-label, active-controlled trial.","volume":"40","author":"Ito","year":"2017","journal-title":"Diabetes Care"},{"issue":"3","key":"ioi230100r25","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s40265-019-1057-0","article-title":"Emerging role of SGLT-2 inhibitors for the treatment of obesity.","volume":"79","author":"Pereira","year":"2019","journal-title":"Drugs"},{"issue":"1","key":"ioi230100r26","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s12325-018-0824-8","article-title":"Body weight considerations in the management of type 2 diabetes.","volume":"36","author":"Apovian","year":"2019","journal-title":"Adv Ther"},{"issue":"1","key":"ioi230100r27","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13098-023-01085-y","article-title":"Effects of SGLT-2 inhibitors on adipose tissue distribution in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.","volume":"15","author":"Wang","year":"2023","journal-title":"Diabetol Metab Syndr"},{"issue":"5","key":"ioi230100r28","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.123130","article-title":"SGLT2 inhibition reprograms systemic metabolism via FGF21-dependent and -independent mechanisms.","volume":"4","author":"Osataphan","year":"2019","journal-title":"JCI Insight"},{"issue":"3","key":"ioi230100r29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151511","article-title":"Ipragliflozin improves hepatic steatosis in obese mice and liver dysfunction in type 2 diabetic patients irrespective of body weight reduction.","volume":"11","author":"Komiya","year":"2016","journal-title":"PLoS One"},{"issue":"12","key":"ioi230100r30","doi-asserted-by":"publisher","first-page":"5175","DOI":"10.1172\/JCI76388","article-title":"Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia.","volume":"124","author":"Cotter","year":"2014","journal-title":"J Clin Invest"},{"issue":"5","key":"ioi230100r31","doi-asserted-by":"publisher","first-page":"305","DOI":"10.7326\/M15-1774","article-title":"Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial.","volume":"165","author":"Cusi","year":"2016","journal-title":"Ann Intern Med"},{"issue":"11","key":"ioi230100r32","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.1111\/liv.v41.11","article-title":"PPAR-?-induced changes in visceral fat and adiponectin levels are associated with improvement of steatohepatitis in patients with NASH.","volume":"41","author":"Gastaldelli","year":"2021","journal-title":"Liver Int"},{"key":"ioi230100r33","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154780","article-title":"Thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, sulfonylureas, and hepatocellular carcinoma risk: a meta-analysis.","volume":"120","author":"Arvind","year":"2021","journal-title":"Metabolism"},{"key":"ioi230100r34","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1182037","article-title":"New anti-diabetic agents for the treatment of non-alcoholic fatty liver disease: a systematic review and network meta-analysis of randomized controlled trials.","volume":"14","author":"Kongmalai","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"7","key":"ioi230100r35","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2022.101970","article-title":"Effect of novel glucose lowering agents on non-alcoholic fatty liver disease: a systematic review and meta-analysis.","volume":"46","author":"Zafar","year":"2022","journal-title":"Clin Res Hepatol Gastroenterol"},{"issue":"1","key":"ioi230100r36","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12933-020-0990-2","article-title":"Favorable pleiotropic effects of sodium glucose cotransporter 2 inhibitors: head-to-head comparisons with dipeptidyl peptidase-4 inhibitors in type 2 diabetes patients.","volume":"19","author":"Shao","year":"2020","journal-title":"Cardiovasc Diabetol"},{"issue":"4","key":"ioi230100r37","doi-asserted-by":"publisher","first-page":"461","DOI":"10.4093\/dmj.2021.0156","article-title":"2021 Clinical practice guidelines for diabetes mellitus of the Korean Diabetes Association.","volume":"45","author":"Hur","year":"2021","journal-title":"Diabetes Metab J"},{"issue":"4","key":"ioi230100r39","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.v33.4","article-title":"Occurrence over time and regression of nonalcoholic fatty liver disease in type 2 diabetes.","volume":"33","author":"Giorda","year":"2017","journal-title":"Diabetes Metab Res Rev"},{"key":"ioi230100r40","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.638615","article-title":"The repeatedly elevated fatty liver index is associated with increased mortality: a population-based cohort study.","volume":"12","author":"Lee","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"7","key":"ioi230100r41","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1007\/s10654-022-00868-3","article-title":"Lifestyle and metabolic factors for nonalcoholic fatty liver disease: Mendelian randomization study.","volume":"37","author":"Yuan","year":"2022","journal-title":"Eur J Epidemiol"},{"issue":"2","key":"ioi230100r42","doi-asserted-by":"publisher","first-page":"263","DOI":"10.2463\/mrms.mp.2021-0168","article-title":"The accuracy and clinical relevance of the multi-echo Dixon technique for evaluating changes to hepatic steatosis in patients with non-alcoholic fatty liver disease treated with formulated food.","volume":"22","author":"Yang","year":"2023","journal-title":"Magn Reson Med Sci"},{"issue":"1","key":"ioi230100r43","doi-asserted-by":"publisher","first-page":"82","DOI":"10.15386\/cjmed-544","article-title":"Prevalence and predictors of non-alcoholic fatty liver disease as defined by the fatty liver index in a type 2 diabetes population.","volume":"89","author":"Silaghi","year":"2016","journal-title":"Clujul Med"},{"key":"ioi230100r44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.09.036","article-title":"Longitudinal changes in fatty liver index are associated with risk of hepatocellular carcinoma: A nationwide cohort study in Korea.","author":"Kang","year":"2023","journal-title":"J Hepatol"},{"issue":"6","key":"ioi230100r45","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1016\/j.jhep.2015.11.004","article-title":"EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease.","volume":"64","author":"European Association for the Study of the Liver (EASL)","year":"2016","journal-title":"J Hepatol"},{"issue":"5","key":"ioi230100r46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100322","article-title":"Non-alcoholic fatty liver disease: a patient guideline.","volume":"3","author":"Francque","year":"2021","journal-title":"JHEP Rep"},{"issue":"6","key":"ioi230100r47","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1007\/s12072-020-10094-2","article-title":"The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.","volume":"14","author":"Eslam","year":"2020","journal-title":"Hepatol Int"},{"key":"ioi230100r48","doi-asserted-by":"publisher","first-page":"S140","DOI":"10.2337\/dc23-S009","article-title":"9. Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2023.","volume":"46","author":"ElSayed","year":"2023","journal-title":"Diabetes Care"},{"key":"ioi230100r38","doi-asserted-by":"crossref","DOI":"10.20517\/mtod.2021.08","volume-title":"The Fatty Liver Index (FLI) 15 Years Later: A Reappraisal","author":"Lonardo","year":"2021"}],"container-title":["JAMA Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamainternalmedicine\/articlepdf\/2814646\/jamainternal_jang_2024_oi_230100_1711137728.84293.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T15:02:29Z","timestamp":1711983749000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamainternalmedicine\/fullarticle\/2814646"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,1]]},"references-count":48,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamainternmed.2023.8029","relation":{},"ISSN":["2168-6106"],"issn-type":[{"value":"2168-6106","type":"print"}],"subject":[],"published":{"date-parts":[[2024,4,1]]}}}