{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:22:04Z","timestamp":1790036524280,"version":"4.0.1"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,9,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Obesity is associated with cardiometabolic disease, including insulin resistance (IR) and diabetes. Cyclic guanosine monophosphate (\n              <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\n              ) signaling affects energy balance, IR, and glucose metabolism in experimental models. We sought to examine effects of phosphodiesterase\u20105 inhibition with tadalafil on IR in a pilot study of obese nondiabetic individuals.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We conducted a randomized, double\u2010blinded, placebo\u2010controlled trial of adults age 18 to 50\u00a0years with obesity and elevated fasting insulin levels (\u226510\u00a0\u03bcU\/\n              <jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>\n              ). Participants were randomized to tadalafil 20\u00a0mg daily or placebo for 3\u00a0months. Oral glucose tolerance tests were performed, and the effect of tadalafil on IR was examined. A total of 53 participants (mean age, 33\u00a0years; body mass index [BMI], 38\u00a0kg\/m\n              <jats:sup>2<\/jats:sup>\n              ) were analyzed, 25 randomized to tadalafil and 28 to placebo. In the overall sample, measures of IR did not differ between tadalafil and placebo groups at 3\u00a0months. However, in individuals with severe obesity (BMI \u226536.2\u00a0kg\/m\n              <jats:sup>2<\/jats:sup>\n              ), tadalafil use was associated with improved IR (homeostatic model assessment for IR), compared to placebo (\n              <jats:italic>P<\/jats:italic>\n              =0.02, respectively). Furthermore, one measure of \u03b2\u2010cell compensation for IR (oral disposition index) improved with tadalafil in the overall sample (\n              <jats:italic>P<\/jats:italic>\n              =0.009) and in the subgroup with severe obesity (\n              <jats:italic>P<\/jats:italic>\n              =0.01).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Results of this pilot study did not show improvements in IR with tadalafil, compared to placebo. However, tadalafil may have favorable effects on \u03b2\u2010cell compensation, particularly in individuals with severe obesity. Future studies evaluating the potential metabolic benefits of\n              <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\n              modulation in obesity are warranted.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Clinical Trial Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">URL: ClinicalTrials.gov. Unique Identifier: NCT01444651.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.114.001001","type":"journal-article","created":{"date-parts":[[2014,9,12]],"date-time":"2014-09-12T06:28:27Z","timestamp":1410503307000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Effect of Phosphodiesterase Inhibition on Insulin Resistance in Obese Individuals"],"prefix":"10.1161","volume":"3","author":[{"given":"Jennifer E.","family":"Ho","sequence":"first","affiliation":[{"name":"Cardiovascular Medicine Section, Department of Medicine, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Arora","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey A.","family":"Walford","sequence":"additional","affiliation":[{"name":"Diabetes Center, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anahita","family":"Ghorbani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mount Auburn Hospital, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek P.","family":"Guanaga","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brigham and Women's Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishnu P.","family":"Dhakal","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel I.","family":"Nathan","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel S.","family":"Buys","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose C.","family":"Florez","sequence":"additional","affiliation":[{"name":"Diabetes Center, Massachusetts General Hospital, Boston, MA"},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Newton\u2010Cheh","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA"},{"name":"Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA"},{"name":"Broad Institute of Harvard and MIT, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Division, Department of Medicine, Vanderbilt University, Nashville, 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