{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:18:15Z","timestamp":1791897495564,"version":"4.3.4"},"reference-count":59,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"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":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite novel therapeutic options, many people with type 2 diabetes (T2D) do not achieve their HbA1c targets. Given the progressive nature of T2D, many individuals not controlled with oral therapy will require advancement to injectable therapy using either a glucagon\u2010like peptide\u20101 receptor agonist (GLP\u20101 RA), recently recommended as a first option, or traditionally a basal insulin. However, premix insulins remain frequently used, either as initial injectable therapy or as intensification from basal insulin. Premix insulin injections can potentially provide significant glycaemic improvements to basal insulin but at the expense of increased hypoglycaemia and weight gain and the need for multiple daily doses, which may affect treatment adherence. Real\u2010world evidence suggests that glycaemic control often remains suboptimal with premix insulins. Fixed\u2010ratio combinations (FRCs) of basal insulin and GLP\u20101 RAs provide a novel alternative to premix insulin for therapy intensification. While no direct comparisons between premix insulins and FRCs are available, results from meta\u2010analyses suggest that FRCs may offer better HbA1c reductions, a lower risk of hypoglycaemia and less weight gain compared with premix insulin in a simplified treatment regimen. A head\u2010to\u2010head trial of T2D treatment intensification with premix insulin and a FRC of basal insulin plus a GLP\u20101 RA is currently in progress, which should help to clarify the outcomes for each treatment option. This review discusses the unmet needs of people with T2D treated with premix insulin and provides evidence supporting FRCs of basal insulin and GLP\u20101 RAs as an alternative treatment option.<\/jats:p>","DOI":"10.1111\/dom.14365","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T09:39:55Z","timestamp":1614677995000},"page":"1445-1452","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Titratable fixed\u2010ratio combination of basal insulin plus a glucagon\u2010like peptide\u20101 receptor agonist: A novel, simplified alternative to premix insulin for type 2 diabetes"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0106-0091","authenticated-orcid":false,"given":"Fernando","family":"Gomez\u2010Peralta","sequence":"first","affiliation":[{"name":"Endocrinology and Nutrition Unit Segovia General Hospital  Segovia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebaa","family":"Al\u2010Ozairi","sequence":"additional","affiliation":[{"name":"Dasman Diabetes Institute  Kuwait City Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-4122","authenticated-orcid":false,"given":"Edward B.","family":"Jude","sequence":"additional","affiliation":[{"name":"Tameside and Glossop Integrated Care NHS Foundation Trust  Ashton\u2010under\u2010Lyne UK"},{"name":"University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8324-3275","authenticated-orcid":false,"given":"Julio","family":"Rosenstock","sequence":"additional","affiliation":[{"name":"Dallas Diabetes Research Center at Medical City  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2017.12.004"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-05078-3"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci18-0033"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc21-S009"},{"key":"e_1_2_12_6_1","unstructured":"National Institute for Clinical Excellence (NICE). Type 2 diabetes in adults: management. 2015.https:\/\/www.nice.org.uk\/guidance\/ng28\/resources\/type-2-diabetes-in-adults-management-pdf-1837338615493. Accessed 30 June 2020."},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2007.07.003"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-015-0044-z"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.01.017"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2018.1484712"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12312"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12407"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-1122"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12609"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2008.00915.x"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2014.09.026"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2008.01792.x"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2009.02064.x"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14298"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12626"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0198160"},{"issue":"1","key":"e_1_2_12_22_1","first-page":"S425","article-title":"Unmet medical needs in people with type 2 diabetes treated by insulin: results from the International Diabetes Management Practices Survey (IDMPS)","volume":"62","author":"Ramachandran A","year":"2019","journal-title":"Diabetologia."},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13132"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2012.03605.x"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1497.2005.0117.x"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.2337\/diaspect.29.3.166"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.30"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13871"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13168"},{"key":"e_1_2_12_30_1","unstructured":"NovoNordisk. Xultophy\u00ae \u2013 Prescribing Information.2019.https:\/\/www.novo-pi.com\/xultophy10036.pdf. Accessed July 9 2020."},{"key":"e_1_2_12_31_1","unstructured":"NovoNordisk. Xultophy\u00ae \u2013 Summary of Product Characteristics.2020. Accessed July 9 2020.https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/xultophy-epar-product-information_en.pdf"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-0917"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-1495"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-1357"},{"key":"e_1_2_12_35_1","article-title":"Translating iGlarLixi evidence for the management of frequent clinical scenarios in type 2 diabetes","author":"Skolnik N","year":"2020","journal-title":"Adv Ther"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14202"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(14)70174-3"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-0785"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-016-0218-3"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13256"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.1252"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12892"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-1114"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30184-6"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13666"},{"key":"e_1_2_12_46_1","unstructured":"Sanofi. Soliqua\u00ae: US prescribing information.2019.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/208673s007lbl.pdf. Accessed July 9 2020."},{"key":"e_1_2_12_47_1","unstructured":"Sanofi. Suliqua\u00ae: EU summary of product characteristics.2020.https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/suliqua-epar-product-information_en.pdf. Accessed July 9 2020."},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2017.1400011"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1080\/13696998.2017.1409228"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14136"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14148"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-019-00730-y"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12097"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163350"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13125"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.10.024"},{"issue":"1","key":"e_1_2_12_57_1","first-page":"e13734","article-title":"Comparison of insulin degludec (IDeg)\/insulin Aspart (IAsp) co\u2010formulation therapy twice\u2010daily with free combination of GLP\u20101 receptor agonist liraglutide plus insulin degludec in Tochigi: IDEAL trial","volume":"69","author":"Aso Y","year":"2020","journal-title":"Int J Clin Pract"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14354"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1262-3636(16)30004-0"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsb1609216"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.14365","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.14365","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.14365","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:37:59Z","timestamp":1761889079000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.14365"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,31]]},"references-count":59,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1111\/dom.14365"],"URL":"https:\/\/doi.org\/10.1111\/dom.14365","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,31]]},"assertion":[{"value":"2020-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}