{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:52:22Z","timestamp":1787025142916,"version":"build-2736575974"},"reference-count":39,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"PROTON","award":["NNF14OC0013659"],"award-info":[{"award-number":["NNF14OC0013659"]}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Renin\u2013angiotensin system (RAS) inhibitors decrease the urinary albumin to creatinine ratio (UACR) but are ineffective in up to 40% of patients. We hypothesized that rotation through different drug classes overcomes RAS inhibitor resistance and tested this in a randomized crossover trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>We assigned 26 adults with type 1 diabetes and 37 with type 2 diabetes and UACR between 30 and 500 mg\/g and estimated glomerular filtration rate &amp;gt;45 mL\/min\/1.73 m2 to 4-week treatment periods with telmisartan 80 mg, empagliflozin 10 mg, linagliptin 5 mg, and baricitinib 2 mg in random order, separated by 4-week washout periods. Each participant was then re-exposed for 4 weeks to the drug that induced that individual\u2019s largest UACR reduction. Primary outcome was the difference in UACR response to the best-performing drug during the confirmation period versus UACR response to the other three drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>There was substantial variation in the best-performing drug. Telmisartan was best performing for 33 participants (52%), empagliflozin and linagliptin in 11 (17%), and baricitinib in 8 participants (13%). The individuals\u2019 best-performing drug changed UACR from baseline during the first and confirmatory exposures by a mean of \u221239.6% (95% CI \u221244.8, \u221233.8; P &amp;lt; 0.001) and \u221222.4% (95% CI \u221229.7, \u221212.5; P &amp;lt; 0.001), respectively. The Pearson correlation for first versus confirmatory exposure was 0.39 (P = 0.017). The mean change in UACR with the other three drugs was +1.6% (95% CI \u22124.3%, 8.0%; P = 0.593 versus baseline; difference versus individuals\u2019 best-performing drug at confirmation, 30.9% [95% CI 18.0, 45.3]; P &amp;lt; 0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>We demonstrated a large and reproducible variation in participants\u2019 responses to different UACR-lowering drug classes. These data support systematic rotation through different drug classes to overcome therapy resistance to RAS inhibition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc22-1699","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T21:30:53Z","timestamp":1674163853000},"page":"593-601","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":28,"title":["Optimization of Albuminuria-Lowering Treatment in Diabetes by Crossover Rotation to Four Different Drug Classes: A Randomized Crossover Trial"],"prefix":"10.2337","volume":"46","author":[{"given":"Viktor Rotbain","family":"Curovic","sequence":"first","affiliation":[{"name":"1Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Jongs","sequence":"additional","affiliation":[{"name":"2Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein Y.A.M.","family":"Kroonen","sequence":"additional","affiliation":[{"name":"2Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie H.","family":"Zobel","sequence":"additional","affiliation":[{"name":"1Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine W.","family":"Hansen","sequence":"additional","affiliation":[{"name":"1Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha","family":"Sen","sequence":"additional","affiliation":[{"name":"2Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gozewijn 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