{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:35:12Z","timestamp":1777386912314,"version":"3.51.4"},"reference-count":35,"publisher":"American Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T00:00:00Z","timestamp":1545264000000},"content-version":"vor","delay-in-days":71,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>This study characterized the pharmacokinetics (PK), pharmacodynamics (PD), and endogenous (hepatic) glucose production (EGP) of clinical doses of glargine U300 (Gla-300) and glargine U100 (Gla-100) under steady-state (SS) conditions in type 1 diabetes mellitus (T1DM).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>T1DM subjects (N = 18, age 40 \u00b1 12 years, T1DM duration 26 \u00b1 12 years, BMI 23.4 \u00b1 2 kg\/m2, A1C 7.19 \u00b1 0.52% [55 \u00b1 5.7 mmol \u00b7 mol\u22121\u22121]) were studied after 3 months of Gla-300 or Gla-100 (evening dosing) titrated to fasting euglycemia (random, crossover) with the euglycemic clamp using individualized doses (Gla-300 0.35 \u00b1 0.08, Gla-100 0.28 \u00b1 0.07 units \u00b7 kg\u22121).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Plasma free insulin concentrations (free immunoreactive insulin area under the curve) were equivalent over 24 h with Gla-300 versus Gla-100 (point estimate 1.11 [90% CI 1.03; 1.20]) but were reduced in the first 6 h (0.91 [90% CI 0.86; 0.97]) and higher in the last 12 h postdosing (1.38 [90% CI 1.21; 1.56]). Gla-300 and Gla-100 both maintained 24 h euglycemia (0.99 [90% CI 0.98; 1.0]). The glucose infusion rate was equivalent over 24 h (1.03 [90% CI 0.88; 1.21]) but was lower in first (0.77 [90% CI 0.62; 0.95]) and higher (1.53 [90% CI 1.23; 1.92]) in the second 12 h with Gla-300 versus Gla-100. EGP was less suppressed during 0\u20136 h but more during 18\u201324 h with Gla-300. PK and PD within-day variability (fluctuation) was 50% and 17% lower with Gla-300.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Individualized, clinical doses of Gla-300 and Gla-100 resulted in a similar euglycemic potential under SS conditions. However, Gla-300 exhibited a more stable profile, with lower variability and more physiological modulation of EGP compared with Gla-100.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc18-0706","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T18:25:34Z","timestamp":1539195934000},"page":"85-92","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":40,"title":["Pharmacokinetics, Pharmacodynamics, and Modulation of Hepatic Glucose Production With Insulin Glargine U300 and Glargine U100 at Steady State With Individualized Clinical Doses in Type 1 Diabetes"],"prefix":"10.2337","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-6734","authenticated-orcid":false,"given":"Francesca","family":"Porcellati","sequence":"first","affiliation":[{"name":"Section of Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Lucidi","sequence":"additional","affiliation":[{"name":"Section of Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Candeloro","sequence":"additional","affiliation":[{"name":"Section of Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Cioli","sequence":"additional","affiliation":[{"name":"Section of Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Marinelli Andreoli","sequence":"additional","affiliation":[{"name":"Section of Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Curti","sequence":"additional","affiliation":[{"name":"Section of Occupational Medicine, Department of Medicine, Perugia University School of Medicine, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4966-4003","authenticated-orcid":false,"given":"Geremia B.","family":"Bolli","sequence":"additional","affiliation":[{"name":"Section of Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmine G.","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Section of Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Perugia, 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