{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:50:48Z","timestamp":1791190248226,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Achievement of low-density lipoprotein cholesterol (LDL-C) targets is crucial for the prevention of atherosclerotic cardiovascular disease (ASCVD). As first-line lipid-lowering drugs, statins often fail to achieve adequate LDL-C control rates in clinical practice due to individual variations in efficacy, safety concerns, and poor long-term adherence. Cholesterol absorption inhibition mediated by the Niemann-Pick C1-like 1 (NPC1L1) pathway provides a complementary approach to statin-based lipid lowering regimens. Hybutimibe is an oral NPC1L1 inhibitor approved in China and has reported pharmacokinetic characteristics that differ from those of ezetimibe; however, the clinical relevance of these differences has not been established in direct comparative studies. Evidence from Phase I-III clinical trials and post-marketing real-world studies indicates that hybutimibe monotherapy or combination therapy with statins can achieve significant and sustained LDL-C reduction; in patients with inadequate response to statin monotherapy, combination with hybutimibe exhibits superior lipid-lowering efficacy compared to statin dose escalation, with favorable overall safety. However, available studies have primarily evaluated LDL-C and other lipid parameters as surrogate endpoints. No dedicated cardiovascular outcome trial has established whether hybutimibe reduces major adverse cardiovascular events, cardiovascular mortality, or all-cause mortality. This article systematically reviews the research and development background, pharmacological properties, mechanism of action, clinical efficacy, safety, and post-marketing real-world evidence of hybutimibe, exploring its application value as an adjuvant therapy in optimizing clinical LDL-C management.<\/jats:p>","DOI":"10.3389\/fphar.2026.1936459","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:51:27Z","timestamp":1791186687000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hybutimibe, an innovative cholesterol absorption inhibitor for lipid-lowering therapy: current evidence and future perspectives"],"prefix":"10.3389","volume":"17","author":[{"given":"Sha","family":"Li","sequence":"first","affiliation":[{"name":"Cardiometabolic Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Cardiometabolic Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Cardiometabolic Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"937","DOI":"10.3969\/j.issn.1000-3614.2016.10.001","article-title":"Chinese guidelines on prevention and treatment of dyslipidemia in adults (2016 revision)","volume":"31","author":"Adults","year":"2016","journal-title":"Chin. 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