{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:00:50Z","timestamp":1791892850836,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Atherosclerotic cardiovascular disease remains a leading cause of global mortality, with low\u2010density lipoprotein cholesterol (LDL\u2010C) reduction being the cornerstone of prevention. Despite effective therapies, many high\u2010risk patients do not achieve recommended LDL\u2010C targets. Enlicitide (MK\u20100616), an oral proprotein convertase subtilisin\/kexin type 9 (PCSK9) inhibitor, offers a potential alternative to injectable PCSK9\u2010directed therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the efficacy and safety of enlicitide in adults with hypercholesterolemia and assess its dose\u2010dependent effects on lipid parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic review and meta\u2010analysis of randomized controlled trials (RCTs) according to PRISMA 2020 guidelines. PubMed, Embase, Scopus, ClinicalTrials.gov, and Google Scholar were searched from inception through March 2026. Random\u2010effects meta\u2010analysis using restricted maximum likelihood estimation was performed. The primary outcome was the percentage change in LDL\u2010C from baseline. Secondary outcomes included non\u2010high\u2010density lipoprotein cholesterol (non\u2010HDL\u2010C), apolipoprotein B (ApoB), lipoprotein(a), triglycerides, and safety outcomes. Risk of bias and certainty of evidence were assessed using RoB 2.0 and GRADE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three placebo\u2010controlled RCTs involving 3593 participants were included. Enlicitide significantly reduced LDL\u2010C compared with placebo (mean difference [MD], \u221256.19%; 95% CI, \u221264.14 to \u221248.25;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), with moderate heterogeneity (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200956.9%). Significant reductions were also observed in non\u2010HDL\u2010C (MD, \u221251.36%), ApoB (MD, \u221247.09%), lipoprotein(a) (MD, \u221220.10%), and triglycerides (MD, \u221213.12%). A numerical dose\u2013response gradient was observed, although subgroup differences were not statistically significant. Sensitivity analyses supported the robustness of the findings. Rates of adverse events, serious adverse events, and treatment discontinuation were comparable between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Enlicitide produced substantial reductions in LDL\u2010C and other atherogenic lipid parameters without an apparent increase in adverse events. However, findings should be interpreted cautiously given the limited number of trials, moderate heterogeneity, and reliance on surrogate endpoints. Dose\u2013response, duration\u2010related lipoprotein(a), and triglyceride findings were exploratory and substantially driven by single trials. Long\u2010term cardiovascular outcomes trials are needed to establish clinical benefit.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70358","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:13:28Z","timestamp":1791890008000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Enlicitide in Hypercholesterolemia: A Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9277-4788","authenticated-orcid":false,"given":"Muhammad","family":"Farhan","sequence":"first","affiliation":[{"name":"Karachi Medical and Dental College  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6621-7986","authenticated-orcid":false,"given":"Muhammad","family":"Murtaza","sequence":"additional","affiliation":[{"name":"Services Institute of Medical Sciences  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2390-8422","authenticated-orcid":false,"given":"Muhammad Mujtaba","family":"Rasool","sequence":"additional","affiliation":[{"name":"Allama Iqbal Medical College  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0806-6897","authenticated-orcid":false,"given":"Farah","family":"Khan","sequence":"additional","affiliation":[{"name":"Allama Iqbal Medical College  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1602-2147","authenticated-orcid":false,"given":"Hammad","family":"Amjad","sequence":"additional","affiliation":[{"name":"Karachi Medical and Dental College  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2135-0673","authenticated-orcid":false,"given":"Kuldeep Dalpat","family":"Rai","sequence":"additional","affiliation":[{"name":"Dow University of Health Sciences  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2223-4488","authenticated-orcid":false,"given":"Sheikh Muhammad Ebtehaj","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Medicine Abbasi Shaheed Hospital  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2930-8188","authenticated-orcid":false,"given":"Ahmed Asad","family":"Raza","sequence":"additional","affiliation":[{"name":"Jinnah Sindh Medical University  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5882-1034","authenticated-orcid":false,"given":"Muhammad Ahmad","family":"Sohail","sequence":"additional","affiliation":[{"name":"Shifa College of Medicine  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8614-3924","authenticated-orcid":false,"given":"Abedin","family":"Samadi","sequence":"additional","affiliation":[{"name":"Kabul University of Medical Sciences Abu Ali Sina  Kabul Afghanistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7543-4638","authenticated-orcid":false,"given":"Furqan","family":"Hassan","sequence":"additional","affiliation":[{"name":"Nishtar Medical University  Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.061010"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpc.2024.100649"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2025.03.518"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615664"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801174"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athplu.2024.11.003"},{"key":"e_1_2_17_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2516860"},{"key":"e_1_2_17_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010025\u201003418\u2010x"},{"key":"e_1_2_17_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.063372"},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2023.02.018"},{"key":"e_1_2_17_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2511002"},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.20620"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2025.03.499"},{"key":"e_1_2_17_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2026.02.002"},{"key":"e_1_2_17_16_1","unstructured":"\u201cClinicalTrials.gov. 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