{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:41:46Z","timestamp":1789789306024,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,5,25]],"date-time":"2014-05-25T00:00:00Z","timestamp":1400976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Macrophage recruitment through C\u2010C motif chemokine receptor\u20102 (CCR2) into adipose tissue is believed to play a role in the development of insulin resistance and type 2 diabetes mellitus (T2DM). The objective of this Phase 2 proof\u2010of\u2010concept study was to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of JNJ\u201041443532, an orally bioavailable CCR2 antagonist, in patients with T2DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a 4\u2010week, double\u2010blind, placebo\u2010controlled, randomized, multicenter study. A total of 89 patients were randomized to receive either 250\u2010 or 1000\u2010mg of JNJ\u201041443532 twice daily, 30\u2010mg of pioglitazone once daily (reference arm), or placebo. The primary endpoint was change from baseline in 23\u2010h weighted mean glucose (WMG); secondary endpoints included change from baseline in fasting plasma glucose (FPG), insulin resistance (Homeostatic Model Assessment [HOMA\u2010IR]), insulin secretion (HOMA\u2010%B) and body weight.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Absorption of JNJ\u201041443532 into the systemic circulation occurred at a median\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      of 2 h, and the mean\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>\u00bd<\/jats:sub>\n                      was approximately 8 h for both doses; plasma systemic exposures increased slightly more than dose\u2010proportionally. After 4 weeks, reductions in 23\u2010h WMG and FPG were observed in all treatment groups compared with placebo and were significantly lower for 250\u2010mg JNJ\u201041443532 and pioglitazone. HOMA\u2010IR was lower for all treatment groups, but significantly lower only for pioglitazone. Conversely, HOMA\u2010%B was increased for all groups, but significantly increased only for 250\u2010mg JNJ\u201041443532. All groups, including placebo, had decreased body weight over time. There were no clinically significant findings during routine safety assessments and the incidence of treatment\u2010emergent adverse events was similar across all groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Administration of JNJ\u201041443532 resulted in modest improvement in glycaemic parameters compared with placebo, and was generally well tolerated in patients with T2DM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.12309","type":"journal-article","created":{"date-parts":[[2014,5,2]],"date-time":"2014-05-02T09:31:00Z","timestamp":1399023060000},"page":"1055-1064","source":"Crossref","is-referenced-by-count":38,"title":["<scp>CCR2<\/scp>\n                    antagonism in patients with type 2 diabetes mellitus: a randomized, placebo\u2010controlled study"],"prefix":"10.1111","volume":"16","author":[{"given":"N. A.","family":"Di Prospero","sequence":"first","affiliation":[{"name":"Department of Translational Medicine Janssen Research &amp; Development  Raritan NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Artis","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Janssen Research &amp; Development  Raritan NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Andrade\u2010Gordon","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery Janssen Research &amp; Development  Spring House PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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