{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:28:12Z","timestamp":1782534492338,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To perform dose\u2013exposure\u2013response analyses to determine the effects of finerenone doses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Two randomized, double\u2010blind, placebo\u2010controlled phase 3 trials enrolling 13\u2009026 randomized participants with type 2 diabetes (T2D) from global sites, each with an estimated glomerular filtration rate (eGFR) of 25 to 90\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      , a urine albumin\u2010creatinine ratio (UACR) of 30 to 5000\u2009mg\/g, and serum potassium \u2264\u20094.8\u2009mmol\/L were included. Interventions were titrated doses of finerenone 10 or 20\u2009mg versus placebo on top of standard of care. The outcomes were trajectories of plasma finerenone and serum potassium concentrations, UACR, eGFR and kidney composite outcomes, assessed using nonlinear mixed\u2010effects population pharmacokinetic (PK)\/pharmacodynamic (PD) and parametric time\u2010to\u2010event models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      For potassium, lower serum levels and lower rates of hyperkalaemia were associated with higher doses of finerenone 20\u2009mg compared to 10\u2009mg (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The PK\/PD model analysis linked this observed inverse association to potassium\u2010guided dose titration. Simulations of a hypothetical trial with constant finerenone doses revealed a shallow but increasing exposure\u2013potassium response relationship. Similarly, increasing finerenone exposures led to less than dose\u2010proportional increasing reductions in modelled UACR. Modelled UACR explained 95% of finerenone's treatment effect in slowing chronic eGFR decline. No UACR\u2010independent finerenone effects were identified. Neither sodium\u2010glucose cotransporter\u20102 (SGLT2) inhibitor nor glucagon\u2010like peptide\u20101 receptor agonist (GLP\u20101RA) treatment significantly modified the effects of finerenone in reducing UACR and eGFR decline. Modelled eGFR explained 87% of finerenone's treatment effect on kidney outcomes. No eGFR\u2010independent effects were identified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The analyses provide strong evidence for the effectiveness of finerenone dose titration in controlling serum potassium elevations. UACR and eGFR are predictive of kidney outcomes during finerenone treatment. Finerenone's kidney efficacy is independent of concomitant use of SGLT2 inhibitors and GLP\u20101RAs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15387","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T02:03:29Z","timestamp":1701396209000},"page":"924-936","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Pharmacokinetics and pharmacodynamics of finerenone in patients with chronic kidney disease and type 2 diabetes: Insights based on\n                    <scp>FIGARO\u2010DKD<\/scp>\n                    and\n                    <scp>FIDELIO\u2010DKD<\/scp>"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-3423","authenticated-orcid":false,"given":"Thomas","family":"Eissing","sequence":"first","affiliation":[{"name":"Bayer AG, Pharmaceuticals R&amp;D, Pharmacometrics  Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3369-6107","authenticated-orcid":false,"given":"Sebastiaan Camiel","family":"Goulooze","sequence":"additional","affiliation":[{"name":"Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&amp;P)  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&amp;P)  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"van Noort","sequence":"additional","affiliation":[{"name":"Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&amp;P)  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"Ruppert","sequence":"additional","affiliation":[{"name":"Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&amp;P)  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1302-678X","authenticated-orcid":false,"given":"Nelleke","family":"Snelder","sequence":"additional","affiliation":[{"name":"Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&amp;P)  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Garmann","sequence":"additional","affiliation":[{"name":"Bayer AG, Pharmaceuticals R&amp;D, Pharmacometrics  Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0683-2874","authenticated-orcid":false,"given":"Joerg","family":"Lippert","sequence":"additional","affiliation":[{"name":"Bayer AG, Pharmaceuticals R&amp;D, Pharmacometrics  Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4645-5428","authenticated-orcid":false,"given":"Roland","family":"Heinig","sequence":"additional","affiliation":[{"name":"Bayer AG, Pharmaceuticals R&amp;D, Clinical Pharmacology  Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1560-9535","authenticated-orcid":false,"given":"Meike","family":"Brinker","sequence":"additional","affiliation":[{"name":"Bayer AG, Pharmaceuticals R&amp;D, Clinical Development  Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J. L.","family":"Heerspink","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110956"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025845"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab777"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.08.040"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2021070942"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.34067\/KID.0000952022"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01083-1"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2021.02.324"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2021.08.001"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2021.02.342"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12049"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-005-0062-y"},{"key":"e_1_2_10_14_1","unstructured":"FDA. Exposure\u2010response relationships\u2010study design data analysis and regulatory applications.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/exposure\u2010response\u2010relationships\u2010study\u2010design\u2010data\u2010analysis\u2010and\u2010regulatory\u2010applications. Accessed February 1 2023."},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000503713"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000503712"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01082-2"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01124-3"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43441-022-00445-6"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00820-x"},{"key":"e_1_2_10_21_1","unstructured":"FDA. Integrated Review Kerendia (Finerenone).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2021\/215341Orig1s000IntegratedR.pdf. Accessed February 12 2023."},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.118.083337"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-022-00770-z"},{"key":"e_1_2_10_24_1","unstructured":"FDA. Kerendia (Finerenone) US Prescribing Information.www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/215341s000lbl.pdf. Accessed February 12 2023."},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12170"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2162"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12746"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-018-0483-9"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000003372"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2019.07.019"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2019.06.009"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2019.08.007"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2022.07.013"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14558"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14883"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2021.10.008"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-0294"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1159\/000516213"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2022020207"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfad249"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13864"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfac198"},{"key":"e_1_2_10_43_1","unstructured":"FDA. Population Pharmacokinetics.https:\/\/www.fda.gov\/media\/128793\/download. Accessed May 23 2023."}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.15387","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T23:23:34Z","timestamp":1761866614000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.15387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,30]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/dom.15387"],"URL":"https:\/\/doi.org\/10.1111\/dom.15387","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,30]]},"assertion":[{"value":"2023-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}