{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T01:46:15Z","timestamp":1794361575714,"version":"4.9.0"},"reference-count":40,"publisher":"BMJ","license":[{"start":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ"],"accepted":{"date-parts":[[2022,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To emulate the GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) trial using real world data before its publication. GRADE directly compared second line glucose lowering drugs for their ability to lower glycated hemoglobin A\n                      <jats:sub>1c<\/jats:sub>\n                      (HbA\n                      <jats:sub>1c<\/jats:sub>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Observational study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>OptumLabs\u00ae Data Warehouse (OLDW), a nationwide claims database in the US, 25 January 2010 to 30 June 2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>\n                      Adults with type 2 diabetes and HbA\n                      <jats:sub>1c<\/jats:sub>\n                      6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>\n                      The primary outcome was time to HbA\n                      <jats:sub>1c<\/jats:sub>\n                      \u22657.0%. Secondary outcomes were time to HbA\n                      <jats:sub>1c<\/jats:sub>\n                      &gt;7.5%, incident microvascular complications, incident macrovascular complications, adverse events, all cause hospital admissions, and all cause mortality. Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      8252 people were identified (19.7% of adults starting the study drugs in OLDW) who met eligibility criteria for the GRADE trial (glimepiride arm=4318, liraglutide arm=690, sitagliptin arm=2993, glargine arm=251). The glargine arm was excluded from analyses owing to small sample size. Median times to HbA\n                      <jats:sub>1c<\/jats:sub>\n                      \u22657.0% were 442 days (95% confidence interval 394 to 480 days) for glimepiride, 764 (741 to not calculable) days for liraglutide, and 427 (380 to 483) days for sitagliptin. Liraglutide was associated with lower risk of reaching HbA\n                      <jats:sub>1c<\/jats:sub>\n                      \u22657.0% compared with glimepiride (hazard ratio 0.57, 95% confidence interval 0.43 to 0.75) and sitagliptin (0.55, 0.41 to 0.73). Results were consistent for the secondary outcome of time to HbA\n                      <jats:sub>1c<\/jats:sub>\n                      &gt;7.5%. No significant differences were observed among treatment groups for the remaining secondary outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this emulation of the GRADE trial, liraglutide was statistically significantly more effective at maintaining glycemic control than glimepiride or sitagliptin when added to metformin monotherapy. Generating timely evidence on medical treatments using real world data as a complement to prospective trials is of value.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmj-2022-070717","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T06:55:37Z","timestamp":1664780137000},"page":"e070717","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Emulating the GRADE trial using real world data: retrospective comparative effectiveness study"],"prefix":"10.1136","volume":"379","author":[{"given":"Yihong","family":"Deng","sequence":"first","affiliation":[{"name":"Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA"},{"name":"OptumLabs, Eden Prairie, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C","family":"Polley","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D","family":"Wallach","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanket S","family":"Dhruva","sequence":"additional","affiliation":[{"name":"Section of Cardiology, San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA"},{"name":"Department of Medicine, UCSF School of Medicine, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeph","family":"Herrin","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT, USA"},{"name":"Flying Buttress Associates, Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Quinto","sequence":"additional","affiliation":[{"name":"Office of Medical Policy, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Springs, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charu","family":"Gandotra","sequence":"additional","affiliation":[{"name":"Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Springs, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Crown","sequence":"additional","affiliation":[{"name":"Florence Heller Graduate School, Brandeis University, Waltham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Noseworthy","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxi","family":"Yao","sequence":"additional","affiliation":[{"name":"Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA"},{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D","family":"Lyon","sequence":"additional","affiliation":[{"name":"Department of Urology, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilay D","family":"Shah","sequence":"additional","affiliation":[{"name":"Delta Air Lines, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph S","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA"},{"name":"Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2289-3183","authenticated-orcid":false,"given":"Rozalina G","family":"McCoy","sequence":"additional","affiliation":[{"name":"Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA"},{"name":"Division of Community Internal Medicine, Geriatrics, and Palliative Care, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"key":"2025110101580813000_379.oct03_5.e070717.1","unstructured":"CDC. National Diabetes Statistics Report Atlanta, Georgia, U.S.A.: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2021 (updated 29 December 2021; cited 26 July 2022]. https:\/\/www.cdc.gov\/diabetes\/data\/statistics-report\/."},{"key":"2025110101580813000_379.oct03_5.e070717.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.107843"},{"key":"2025110101580813000_379.oct03_5.e070717.3","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d6898"},{"key":"2025110101580813000_379.oct03_5.e070717.4","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l5887"},{"key":"2025110101580813000_379.oct03_5.e070717.5","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-S006"},{"key":"2025110101580813000_379.oct03_5.e070717.6","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-008-0554-8"},{"key":"2025110101580813000_379.oct03_5.e070717.7","first-page":"B21","article-title":"Long-term results of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients","volume":"23","author":"Shichiri","year":"2000","journal-title":"Diabetes Care"},{"key":"2025110101580813000_379.oct03_5.e070717.8","doi-asserted-by":"publisher","DOI":"10.1001\/jama.281.21.2005"},{"key":"2025110101580813000_379.oct03_5.e070717.9","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.321.7258.405"},{"key":"2025110101580813000_379.oct03_5.e070717.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0806470"},{"key":"2025110101580813000_379.oct03_5.e070717.11","unstructured":"NICE. National Institute for Health and Care Excellence Pathways: Managing Blood Glucose in Adults with Type 2 Diabetes: National Institute for Health and Care Excellence; 2019 (updated 26 March 2019; cited 23 April 2019). https:\/\/pathways.nice.org.uk\/pathways\/type-2-diabetes-in-adults."},{"key":"2025110101580813000_379.oct03_5.e070717.12","doi-asserted-by":"publisher","DOI":"10.4158\/CS-2018-0535"},{"key":"2025110101580813000_379.oct03_5.e070717.13","doi-asserted-by":"publisher","DOI":"10.7326\/M17-1362"},{"key":"2025110101580813000_379.oct03_5.e070717.14","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-S009"},{"key":"2025110101580813000_379.oct03_5.e070717.15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa2032271"},{"key":"2025110101580813000_379.oct03_5.e070717.16","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0356"},{"key":"2025110101580813000_379.oct03_5.e070717.17","unstructured":"ClinicalTrials.gov. A Comparative Effectiveness Study of Major Glycemia-lowering Medications for Treatment of Type 2 Diabetes (GRADE). ClinicalTrials.gov Identifier: NCT01794143: U.S. National Library of Medicine. National Institutes of Health. Department of Health and Human Services; 2021 (updated 30 June 2021; cited 7 September 2021). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01794143"},{"key":"2025110101580813000_379.oct03_5.e070717.18","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.30587"},{"key":"2025110101580813000_379.oct03_5.e070717.19","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-0901"},{"key":"2025110101580813000_379.oct03_5.e070717.20","doi-asserted-by":"publisher","DOI":"10.1377\/hlthaff.2014.0038"},{"key":"2025110101580813000_379.oct03_5.e070717.21","unstructured":"OptumLabs. OptumLabs and OptumLabs Data Warehouse (OLDW) Descriptions and Citation. Cambridge, MA: May 2019. 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