{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T01:02:23Z","timestamp":1780707743972,"version":"3.54.1"},"reference-count":0,"publisher":"American Diabetes Association","issue":"Supplement_1","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6,5]]},"abstract":"<jats:p>Introduction and Objective: GLP-1 receptor agonists (GLP-1RAs) effectively treat type 2 diabetes and obesity but frequent injections may limit adherence. PT403 is a long-acting semaglutide formulation based on biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres designed for once-monthly administration. This study evaluated the pharmacological efficacy, safety, and tolerability of PT403 and explored its translational development potential as a once-monthly semaglutide formulation.<\/jats:p>\n                  <jats:p>Methods: PT403 was formulated by encapsulating semaglutide in biodegradable PLGA microspheres using ultrasonic spray-drying for sustained release. Preclinical efficacy was evaluated in a high-fat diet-induced obesity (DIO) mouse model with dosing regimens maintaining equivalent daily exposure while varying injection intervals. In a randomized, open-label pilot study, 16 healthy adults received either weekly semaglutide (0.5 mg once weekly for four weeks; n=8) or a single subcutaneous dose of PT403 (4 mg; n=8). Safety and adverse events were monitored for 57 days.<\/jats:p>\n                  <jats:p>Results: In the DIO mouse model, PT403 demonstrated sustained body weight reduction. A -30% reduction at week 4 was achieved in the PT403 Q2W and Q3W groups, whereas semaglutide QD and Q3D groups did not reach this target. In the pilot study, 69 adverse events were reported (PT403: 27; reference: 33). Therapeutic intervention was required for 45.5% of ADRs with weekly semaglutide vs 29.6% with PT403. Nausea and vomiting occurred with weekly semaglutide but not with PT403. PT403 ADRs were mild injection-site reactions and decreased appetite. No serious adverse events were reported.<\/jats:p>\n                  <jats:p>Conclusion: PT403 demonstrated sustained pharmacodynamic efficacy in preclinical models and favorable safety and tolerability in a pilot study. These findings suggest that PT403 has the potential to be developed as a differentiated long-acting GLP-1RA formulation that may reduce injection burden, improve tolerability, and enhance long-term treatment adherence.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Disclosure<\/jats:title>\n                    <jats:p>M. Choi: None. H. Jeong: None. S. Kim: Employee; Current; Peptron. Y. Shin: None. J. Lee: None. S.W. Kim: None. S. Chang: None. H. Choi: None.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db26-2847-lb","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:29:32Z","timestamp":1780705772000},"update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["2847-LB: PT403, a Once-Monthly Long-Acting Semaglutide: Preclinical Efficacy and Interim Safety and Tolerability in Healthy Subjects"],"prefix":"10.2337","volume":"75","author":[{"given":"MYUNG-JOO","family":"CHOI","sequence":"first","affiliation":[{"name":"Daejeon, Republic of Korea, Seoul, Republic of Korea, Cheongju-si, Republic of Korea, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HYUNJU","family":"JEONG","sequence":"additional","affiliation":[{"name":"Daejeon, Republic of Korea, Seoul, Republic of Korea, Cheongju-si, Republic of Korea, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SU HEE","family":"KIM","sequence":"additional","affiliation":[{"name":"Daejeon, Republic of Korea, Seoul, Republic of Korea, Cheongju-si, Republic of Korea, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YOUNGHEE","family":"SHIN","sequence":"additional","affiliation":[{"name":"Daejeon, Republic of Korea, Seoul, Republic of Korea, Cheongju-si, Republic of Korea, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JIHYANG","family":"LEE","sequence":"additional","affiliation":[{"name":"Daejeon, Republic of Korea, Seoul, Republic of Korea, Cheongju-si, Republic of Korea, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SUNGWON W.","family":"KIM","sequence":"additional","affiliation":[{"name":"Daejeon, Republic of Korea, Seoul, Republic of Korea, Cheongju-si, Republic of Korea, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SEUNG-GU","family":"CHANG","sequence":"additional","affiliation":[{"name":"Daejeon, Republic of Korea, Seoul, Republic of Korea, Cheongju-si, Republic of Korea, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HOIL","family":"CHOI","sequence":"additional","affiliation":[{"name":"Daejeon, Republic of Korea, Seoul, Republic of Korea, Cheongju-si, Republic of Korea, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/75\/Supplement_1\/2847-LB\/167779\/2847-LB-PT403-a-Once-Monthly-Long-Acting","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/75\/Supplement_1\/2847-LB\/167779\/2847-LB-PT403-a-Once-Monthly-Long-Acting","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:29:32Z","timestamp":1780705772000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/75\/Supplement_1\/2847-LB\/167779\/2847-LB-PT403-a-Once-Monthly-Long-Acting"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":0,"journal-issue":{"issue":"Supplement_1","published-print":{"date-parts":[[2026,6,5]]}},"URL":"https:\/\/doi.org\/10.2337\/db26-2847-lb","relation":{},"ISSN":["0012-1797"],"issn-type":[{"value":"0012-1797","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6,5]]},"article-number":"2847-LB"}}