{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:47:21Z","timestamp":1787021241036,"version":"build-2736575974"},"reference-count":28,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MBX Biosciences, Inc., of Carmel, Indiana"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>After weight-loss surgery, some patients experience postbariatric hypoglycemia (PBH). Although PBH is customarily managed by dietary modifications with continuous glucose monitoring, advanced treatment options are needed. Imapextide is a sustained-action, selective, reversible glucagon-like peptide-1 (GLP-1) receptor antagonist designed for once-weekly administration for PBH treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This work aimed to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple ascending doses (SAD\/MAD) of imapextide in healthy volunteers (HVs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This 3-part, phase 1, double-blind study enrolled healthy adults. In the SAD\/MAD parts, randomly assigned participants (3:1) received subcutaneous imapextide (SAD, 10-200\u2005mg; MAD, 10-30\u2005mg once weekly, 4 doses) or placebo. The primary end point was safety\/tolerability (treatment-emergent adverse events [TEAEs]). PK (SAD\/MAD; time-to-maximal concentration [tmax] and half-life [t1\/2]) and PD (MAD; GLP-1 and glycemic parameters during a mixed meal tolerance test [MMTT]) were assessed. Imapextide drug-drug interactions (DDIs) of OATP1B1\/OATP1B3 inhibition and accelerated gastric emptying were evaluated with coproporphyrin-I, rosuvastatin, and acetaminophen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 69 HVs were randomly assigned (32 SAD, 23 MAD, 14 DDIs). Imapextide TEAE rates ranged from 33.3% to 50.0% (SAD), 33.3% to 100% (MAD), and 14.3% (DDIs) across cohorts. The most common TEAEs included injection site erythema (SAD, MAD) and injection site swelling (MAD). Imapextide exposure was dose proportional (median tmax 24-48 hours; mean t1\/2 \u223c90\u2005hours). During the MMTT, imapextide increased GLP-1 concentrations at early time points, while effects on other glycemic parameters were variable. Minimal nonclinically relevant DDIs occurred with rosuvastatin. Imapextide slightly accelerated gastric emptying.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Imapextide was generally well tolerated in HVs. PK findings supported weekly dosing. PD showed consistent effects on GLP-1 levels, supporting a potential role for imapextide in modulating PBH pathophysiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf691","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T12:54:26Z","timestamp":1766494466000},"page":"1628-1639","source":"Crossref","is-referenced-by-count":2,"title":["Sustained Action of Imapextide, A Glucagon-Like Peptide-1 Receptor Antagonist, in Healthy Volunteers"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9877-4750","authenticated-orcid":false,"given":"Elisa","family":"Fabbrini","sequence":"first","affiliation":[{"name":"MBX Biosciences, Inc. , Carmel, IN 46032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiya","family":"Koshkina","sequence":"additional","affiliation":[{"name":"MBX Biosciences, Inc. , Carmel, IN 46032 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Inc. , Chula Vista, CA 91911 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9244-0596","authenticated-orcid":false,"given":"Kristi","family":"Schneider","sequence":"additional","affiliation":[{"name":"MBX Biosciences, Inc. , Carmel, IN 46032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"D\u2019Alessio","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University , Durham, NC 27701 ,","place":["USA"]},{"name":"Department of Medicine, Duke University , Durham, NC 27701 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D","family":"DiMarchi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Indiana University , Bloomington, IN 47405 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