{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:38:41Z","timestamp":1761896321785},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T00:00:00Z","timestamp":1471305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>The integrated glucose\u2013insulin (IGI) model is a semi\u2010mechanistic physiological model which can describe the glucose\u2013insulin homeostasis system following various glucose challenge settings. The aim of the present work was to apply the model to a large and diverse population of metformin\u2010only\u2010treated type 2 diabetes mellitus (T2DM) patients and identify patient\u2010specific covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from four clinical studies were pooled, including glucose and insulin concentration\u2013time profiles from T2DM patients on stable treatment with metformin alone following mixed\u2010meal tolerance tests. The data were collected from a wide range of patients with respect to the duration of diabetes and level of glycaemic control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The IGI model was expanded by four patient\u2010specific covariates. The level of glycaemic control, represented by baseline glycosylated haemoglobin was identified as a significant covariate for steady\u2010state glucose, insulin\u2010dependent glucose clearance and the magnitude of the incretin effect, while baseline body mass index was a significant covariate for steady\u2010state insulin levels. In addition, glucose dose was found to have an impact on glucose absorption rate. The developed model was used to simulate glucose and insulin profiles in different groups of T2DM patients, across a range of glycaemic control, and it was found accurately to characterize their response to the standard oral glucose challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The IGI model was successfully applied to characterize differences between T2DM patients across a wide range of glycaemic control. The addition of patient\u2010specific covariates in the IGI model might be valuable for the future development of antidiabetic treatment and for the design and simulation of clinical studies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13069","type":"journal-article","created":{"date-parts":[[2016,7,23]],"date-time":"2016-07-23T09:36:39Z","timestamp":1469266599000},"page":"1613-1624","source":"Crossref","is-referenced-by-count":4,"title":["Application of the integrated glucose\u2013insulin model for cross\u2010study characterization of T2DM patients on metformin background treatment"],"prefix":"10.1111","volume":"82","author":[{"given":"Joanna","family":"Parkinson","sequence":"first","affiliation":[{"name":"Cardiovascular &amp; Metabolic Disease Innovative Medicines and Early Development Biotech Unit, AstraZeneca  M\u00f6lndal 431 83 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bengt","family":"Hamr\u00e9n","sequence":"additional","affiliation":[{"name":"Cardiovascular &amp; Metabolic Disease Innovative Medicines and Early Development Biotech Unit, AstraZeneca  M\u00f6lndal 431 83 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria C.","family":"Kjellsson","sequence":"additional","affiliation":[{"name":"Pharmacometrics Research Group, Department of Pharmaceutical Biosciences Uppsala University  Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanko","family":"Skrtic","sequence":"additional","affiliation":[{"name":"Cardiovascular &amp; Metabolic Disease Innovative Medicines and Early Development Biotech Unit, AstraZeneca  M\u00f6lndal 431 83 Sweden"},{"name":"Department of Endocrinology Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,8,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001250100580"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)61032-X"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-002-1009-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1979.236.6.E667"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.2337\/diab.29.12.979","article-title":"Quantitative estimation of beta cell sensitivity to glucose in the intact organism: a minimal model of insulin kinetics in the dog","volume":"29","author":"Toffolo G","year":"1980","journal-title":"Diabetes"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00421.2006"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.5.3.148"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1997.273.5.E1024"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009341185"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007304457"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010362536"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007302168"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.11"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-012-9287-8"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.270"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011422231"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-012-9281-1"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-012-9286-9"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.86"},{"key":"e_1_2_9_23_1","first-page":"S192","article-title":"A mathematical disease progression model for the effect of diet and exercise in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study (FDPS)","volume":"58","author":"Ghadzi SMS","year":"2015","journal-title":"Diabetologia"},{"key":"e_1_2_9_24_1","unstructured":"Study NCT00477581. 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