{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:41:21Z","timestamp":1792384881151,"version":"4.4.0"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To evaluate the efficacy and safety of oral PCSK9 inhibitors in adults with hypercholesterolemia by synthesizing evidence from randomised controlled trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This systematic review and meta\u2010analysis followed PRISMA guidelines and was registered on PROSPERO (CRD420261303350). PubMed, Embase and Scopus were searched from inception to March 2026 for randomised controlled trials comparing oral PCSK9 inhibitors with placebo in adults with hypercholesterolemia. Primary outcomes were changes in low\u2010density lipoprotein cholesterol (LDL\u2010C) and triglycerides. Secondary outcomes included other lipid parameters, adverse events and mortality. Random\u2010effects models were used to calculate mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI). Quality of the included studies was assessed using the RoB2 tool and certainty of evidence was assessed using the GRADE approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five randomised controlled trials (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094268) were included. Oral PCSK9 inhibitors significantly reduced LDL\u2010C (MD \u221249.49\u2009mg\/dL; 95% CI \u221254.81 to \u221244.18;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.00001) and triglycerides (MD \u221211.65\u2009mg\/dL; 95% CI \u221215.53 to \u22127.78;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.00001). Significant reductions were also observed in non\u2010HDL cholesterol, apolipoprotein B, lipoprotein(a) and total\u00a0cholesterol. Dose\u2010dependent effects were noted, with greater reductions at higher doses. No significant differences were\u00a0observed in mortality or overall adverse events. Treatment discontinuation due to adverse events was lower with intervention.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral PCSK9 inhibitors were associated with clinically meaningful improvements in multiple lipid parameters while maintaining a favourable short\u2010term safety profile. However, the available evidence is derived primarily from short\u2010term randomised trials evaluating surrogate lipid outcomes. Larger randomised trials with longer follow\u2010up and cardiovascular outcome data are needed to better define the long\u2010term clinical role of oral PCSK9 inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71208","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T02:04:13Z","timestamp":1786413853000},"page":"10001-10017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Oral\n                    <scp>PCSK9<\/scp>\n                    Inhibitors in Adults With Hypercholesterolemia: An Updated and\n                    <scp>GRADE<\/scp>\n                    Assessed Systematic Review and Meta\u2010Analysis of Randomised Controlled Trials"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5426-924X","authenticated-orcid":false,"given":"Muhammad Huzaifa","family":"Khattak","sequence":"first","affiliation":[{"name":"Department of Medicine Khyber Medical College  Peshawar Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohana","family":"Memon","sequence":"additional","affiliation":[{"name":"Department of Medicine Liaquat University of Medical and Health Sciences  Jamshoro Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Bibi","sequence":"additional","affiliation":[{"name":"Department of Medicine Khyber Medical College  Peshawar Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irshad Munir","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Medicine Jinnah Sindh Medical University  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javaria","family":"Gul","sequence":"additional","affiliation":[{"name":"Department of Medicine Khyber Medical College  Peshawar Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosar","family":"Ajmal","sequence":"additional","affiliation":[{"name":"Department of Medicine Khyber Girls Medical College  Peshawar Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneeq Mahmood","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Medicine Sargodha Medical College  Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyal","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Medicine Gomal Medical College  Dera Ismail Khan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Saqlain","family":"Saleem","sequence":"additional","affiliation":[{"name":"Department of Medicine Allied Hospital  Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Bilal","family":"Yousuf","sequence":"additional","affiliation":[{"name":"Department of Medicine Foundation University Medical College  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasir","family":"Mehmood","sequence":"additional","affiliation":[{"name":"Department of Medicine Federal Government Polyclinic  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hareem","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Medicine Yusra Medical and Dental College  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehr","family":"Afroz","sequence":"additional","affiliation":[{"name":"Department of Medicine Sindh Institute of Urology and Transplantation  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik Muhammad Nasr","family":"Fayyaz","sequence":"additional","affiliation":[{"name":"Department of Medicine Khyber Medical College  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