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The synergistic action of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and metformin may reduce the cardiovascular risk by modulating OCN-expressing monocytes, representing a novel mechanism of cardiovascular protection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To investigate the impact of GLP-1 RA add-on metformin therapy on the percentage of circulating CD14\n                      <jats:sup>+<\/jats:sup>\n                      OCN\n                      <jats:sup>+<\/jats:sup>\n                      monocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research design and methods<\/jats:title>\n                    <jats:p>This longitudinal study enrolled patients with T2D receiving metformin monotherapy who either initiated GLP-1 RA therapy (Group A, n = 7) or did not (Group B, n = 28). Clinical parameters and circulating CD14+OCN+ cell levels were assessed at baseline (V0), after 1\u00a0week (V1) and after 12\u00a0weeks (V2). In vitro experiments were conducted using peripheral blood mononuclear cells (PBMCs) from healthy volunteers (n = 10), treated with metformin or exendin-4 for 24\u00a0h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In group A, the percentage of CD14+OCN+ significantly decreased from baseline (4.5 [2.5\u20137.6]) to V2 (2.2 [1.73\u20134.9]% p = 0.019). This reduction was already significant at V1 (p = 0.039). No significant change over time was observed in Group B (p = 0.31). In vitro treatment of PBMCs with metformin significantly reduced the percentage of CD14\n                      <jats:sup>+<\/jats:sup>\n                      OCN\n                      <jats:sup>+<\/jats:sup>\n                      cell (\u2212\u200934.9%, p &lt; 0.0001), whereas exendin-4 yielded a non-significant downward trend (\u2212\u20098.5%, p = 0.1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GLP-1 RA add-on therapy to metformin reduces OCN expression in circulating monocytes in patients with T2D. In vitro data suggest that this effect might not result from a direct effect on mononuclear cells, but rather from indirect systemic mechanisms that warrant further investigation. These findings identify OCN-expressing monocytes as a potential novel therapeutic target for GLP-1 RA to reduce cardiovascular risk in T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00592-026-02778-2","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:40:55Z","timestamp":1789976455000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of circulating osteocalcin-expressing monocytes by glucagon like peptide-1 receptor agonists in type 2 diabetes: an exploratory pilot study"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7240-8402","authenticated-orcid":false,"given":"Andrea","family":"Carafa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4249-9802","authenticated-orcid":false,"given":"Rosario Luigi","family":"Sessa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Amendolara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Zampetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Mignogna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sciarra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"D\u2019Onofrio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Risi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Anna","family":"Venneri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Cavallari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-9463","authenticated-orcid":false,"given":"Ernesto","family":"Maddaloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Buzzetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"issue":"2","key":"2778_CR1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.2337\/dc24-1455","volume":"48","author":"E Maddaloni","year":"2025","unstructured":"Maddaloni E, Nguyen M, Shah SH, Holman RR (2025) Osteoprotegerin, osteopontin, and osteocalcin are associated with cardiovascular events in type 2 diabetes: insights from EXSCEL. 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