{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:18:35Z","timestamp":1788153515111,"version":"build-2803163510"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Aims\/background<\/jats:title>\n                    <jats:p>Early insulin initiation in type 2 diabetes mellitus (T2DM) is proposed to improve glycemic control, preserve \u03b2-cell function, and potentially reduce long-term complications. Evidence suggests that starting insulin within five years of diagnosis may offer additional metabolic benefits, but its clinical impact remains uncertain. This systematic review aimed to evaluate the efficacy, safety, and challenges of early insulin use in T2DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, Cochrane Library, Scopus, and Controlled Trials Register for studies published from 2010 to 2024, including adults with T2DM who initiated insulin within five years of diagnosis. Sixteen studies met inclusion criteria (9 RCTs, 7 observational), totaling 44, 045 participants. Two reviewers independently extracted data on glycemic outcomes, adverse events, and long-term complications. Risk of bias was assessed using the Cochrane tool for RCTs and the JBI checklist for observational studies. Due to substantial clinical and methodological heterogeneity, a meta-analysis was not performed, and findings were synthesized narratively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Early insulin therapy significantly reduced HbA1c (by 0.8\u20132.3%, p&amp;lt;0.05) and fasting glucose (by 1.2\u20132.4 mmol\/L). Hypoglycemia occurred in 8\u201315% of insulin users compared to 3\u201310% with oral agents; severe episodes were rare (&amp;lt;2%). Weight gain over 2\u00a0kg was reported in nearly half of the studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Early insulin initiation improves glycemic outcomes and may preserve \u03b2-cell function. However, increased risks of hypoglycemia and weight gain warrant individualized treatment decisions. Future studies should adopt standardized definitions and assess long-term cardiovascular outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n                      , identifier CRD42024508356.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1843227","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:28:44Z","timestamp":1788150524000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early insulin initiation in type 2 diabetes: efficacy, safety, and clinical implications: a systematic review with narrative synthesis"],"prefix":"10.3389","volume":"17","author":[{"given":"Osama","family":"Albasheer","sequence":"first","affiliation":[{"name":"Department of Family and Community Medicine, College of Medicine, Jazan University","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal H.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Jazan University","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagla","family":"Abdalghani","sequence":"additional","affiliation":[{"name":"Respiratory Therapy Department, Faculty of Applied Medical Science, Jazan University","place":["Jazan, Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Areej","family":"Hamdi","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Diabetic Center, King Fahad Central Hospital, Ministry of Health","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa Abdulwahab Mohammed","family":"Ayish","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical and Rheumatology Consultant, Head of Medical Department, Jazan General Hospital","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Ayish","sequence":"additional","affiliation":[{"name":"Respiratory Therapy Department, Faculty of Applied Medical Science, Jazan University","place":["Jazan, Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayyub","family":"Alssum","sequence":"additional","affiliation":[{"name":"Family Medicine, Primary Healthcare, Ministry of Health","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Yahya","family":"Maashi","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Jazan University Hospital, Jazan University","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamyaa A. M.","family":"El Hassan","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Jazan University","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahani","family":"Madkhali","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Diabetic Center, King Fahad Central Hospital, Ministry of Health","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Muqri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical Consultant, Jazan Military Hospital","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha A.","family":"Awaf","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Diabetic Center, King Fahad Central Hospital, Ministry of Health","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatim","family":"Alessa","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Jazan University Hospital, Jazan University","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afnan","family":"Madkhali","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Jazan University Hospital, Jazan University","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afaf","family":"Hakami","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Jazan University Hospital, Jazan University","place":["Jazan, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-024-01568-9","article-title":"Barriers to the use of insulin therapy and potential solutions: a narrative review of perspectives from the Asia\u2013Pacific region","volume":"15","author":"Chen","year":"2024"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1366368","article-title":"Current barriers to initiating insulin therapy in individuals with type 2 diabetes","volume":"15","author":"Gald\u00f3n Sanz-Pastor","year":"2024","journal-title":"Front Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-2170","article-title":"\u03b2-cell function preservation after 3.5 years of intensive diabetes therapy","volume":"35","author":"Harrison","year":"2012"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2337\/diaspect.25.3.154","article-title":"Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"25","author":"Inzucchi","year":"2012","journal-title":"Diabetes Spectr"},{"key":"B5","doi-asserted-by":"publisher","first-page":"193","DOI":"10.2337\/dc08-2195","article-title":"Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes","volume":"32","author":"Nathan","year":"2009","journal-title":"Diabetes Care"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13332","article-title":"HbA1c response after insulin initiation in patients with type 2 diabetes mellitus in real life practice: identifying distinct subgroups","volume":"20","author":"Sidorenkov","year":"2018","journal-title":"Diabetes Obes Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14421\/v2\/response1","article-title":"Short-term intensive insulin as induction and maintenance therapy for the preservation of beta-cell function in early type 2 diabetes (RESET-IT Main): a 2-year randomized controlled trial","volume":"23","author":"Retnakaran","year":"2021","journal-title":"Diabetes Obes Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2013.0081","article-title":"Clinical evidence for the earlier initiation of insulin therapy in type 2 diabetes","volume":"15","author":"Owens","year":"2013","journal-title":"Diabetes Technol Ther"},{"key":"B9","doi-asserted-by":"publisher","first-page":"9352","DOI":"10.3390\/ijms24119352","article-title":"Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections","volume":"24","author":"Gonz\u00e1lez","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802743","article-title":"Effects of intensive glucose lowering in type 2 diabetes","volume":"358","author":"Gerstein","year":"2008","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.ecl.2017.10.002","article-title":"Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes mellitus","volume":"47","author":"Kirkman","year":"2018","journal-title":"Endocrinol Metab Clin North Am"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2009.02.026","article-title":"Glucose control and vascular complications in veterans with type 2 diabetes","volume":"360","author":"Duckworth","year":"2009"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2337\/dci18-0002","article-title":"Diabetes technology update: use of insulin pumps and continuous glucose monitoring in the hospital","volume":"41","author":"Umpierrez","year":"2018","journal-title":"Diabetes Care"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1177\/1932296821991136","article-title":"Continuous subcutaneous insulin infusions vs. multiple daily injections of insulin in hospitalized patients: glycemic trends in the first 24 hours of admission","volume":"16","author":"Halstrom","year":"2022","journal-title":"J Diabetes Sci Technol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/ph15080953","article-title":"Continuous subcutaneous insulin infusion (csii) combined with oral glucose-lowering drugs in type 2 diabetes: a systematic review and network meta-analysis of randomized, controlled trials","volume":"15","author":"Li","year":"2022","journal-title":"Pharmaceuticals"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2021.0065","article-title":"Comparison of prevailing insulin regimens at different time periods in hospitalized patients: a real-world experience from a tertiary hospital","volume":"46","author":"Moon","year":"2022","journal-title":"Diabetes Metab J"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa0905479","article-title":"Three-year efficacy of complex insulin regimens in type 2 diabetes","volume":"361","author":"Holman","year":"2009"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-020-01436-5","article-title":"Reduced hypoglycemia risk in type 2 diabetes patients switched to\/initiating insulin glargine 300 vs 100 U\/ml: a European real-world study","volume":"37","author":"Escalada","year":"2020","journal-title":"Adv Ther"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12086","article-title":"Effects of insulin changes on quality of life and glycemic control in Japanese patients with type 2 diabetes mellitus: the insulin\u2010changing study intending to gain patients' insights into insulin treatment with patient\u2010reported health outcomes in actual clinical treatments (INSIGHTS) study","volume":"4","author":"Ishii","year":"2013","journal-title":"J Diabetes Invest"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2753.2010.01552.x","article-title":"Effect of short\u2010term intensive insulin therapy on quality of life in type 2 diabetes","volume":"18","author":"Opsteen","year":"2012"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.183472","article-title":"Impact of insulin pump on quality of life of diabetic patients","volume":"20","author":"Ghazanfar","year":"2016","journal-title":"Indian J Endocrinol Metab"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.38","article-title":"Cochrane handbook for systematic reviews for interventions, Version 5.1. 0, published 3\/2011. Julian PT Higgins and Sally Green, Editors","volume":"2","author":"Shuster","year":"2011"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.11124\/JBIES-24-00103","article-title":"The revised JBI critical appraisal tool for the assessment of risk of bias for cohort studies","volume":"23","author":"Barker","year":"2025","journal-title":"JBI Evidence Synthesis"},{"key":"B25","volume-title":"The GRADE handbook","author":"Guyatt","year":"2013"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2147\/PPA.S51299","article-title":"Determinants and consequences of insulin initiation for type 2 diabetes in France: analysis of the National Health and Wellness Survey","volume":"7","author":"Reach","year":"2013","journal-title":"Patient Prefer Adherence"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.6020.1252","article-title":"Beta-cell function improved by supplementing basal insulin secretion in mild diabetes","volume":"1","author":"Turner","year":"1976"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.2337\/diab.34.3.222","article-title":"The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus","volume":"34","author":"Timothy Garvey","year":"1985"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.5951","article-title":"Insulin therapy for type 2 diabetes mellitus","volume":"311","author":"Wallia","year":"2014"},{"key":"B30","article-title":"Type 2 diabetes subgroups and response to glucose\u2010lowering therapy: results from the EDICT and Qatar studies","volume":"24","author":"Abdul\u2010Ghani","year":"2022"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2337\/figshare.16722358.v1","article-title":"Cluster analysis of cardiovascular phenotypes in patients with type 2 diabetes and established atherosclerotic cardiovascular disease: a potential approach to precision medicine","volume":"45","author":"Sharma","year":"2022"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13528","article-title":"The association of basal insulin treatment versus standard care with outcomes in anti\u2010GAD positive and negative subjects: a post\u2010hoc analysis of the ORIGIN trial","volume":"21","author":"Birkeland","year":"2019"},{"key":"B33","doi-asserted-by":"publisher","first-page":"110012","DOI":"10.1016\/j.diabres.2022.110012","article-title":"Distribution and characteristics of newly-defined subgroups of type 2 diabetes in randomised clinical trials: post hoc cluster assignment analysis of over 12,000 study participants","volume":"190","author":"Landgraf","year":"2022"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-013-0366-z","article-title":"Insulin use early in the course of type 2 diabetes mellitus: the ORIGIN trial","volume":"13","author":"Hanefeld","year":"2013"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12438","article-title":"New insulin glargine 300 U\/ml compared with glargine 100 U\/ml in insulin\u2010naive people with type 2 diabetes on oral glucose\u2010lowering drugs: a randomized controlled trial (EDITION 3)","volume":"17","author":"Bolli","year":"2015"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4158\/ep09281.or","article-title":"Improved glycemic control with insulin glargine versus pioglitazone as add-on therapy to sulfonylurea or metformin in patients with uncontrolled type 2 diabetes mellitus","volume":"16","author":"Meneghini","year":"2010"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-2294","article-title":"A 24-week, randomized, treat-to-target trial comparing initiation of insulin glargine once-daily with insulin detemir twice-daily in patients with type 2 diabetes inadequately controlled on oral glucose-lowering drugs","volume":"33","author":"Swinnen","year":"2010"},{"key":"B38","article-title":"EARLY study: early basal insulin therapy under real-life conditions in type 2 diabetics","volume":"21","author":"Hanefeld","year":"2012","journal-title":"Diabetes Stoffwechsel und Herz"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-021-05567-4","article-title":"Validation of the classification for type 2 diabetes into five subgroups: a report from the ORIGIN trial","volume":"65","author":"Pigeyre","year":"2022"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-2105","article-title":"Short-term intensive therapy in newly diagnosed type 2 diabetes partially restores both insulin sensitivity and \u03b2-cell function in subjects with long-term remission","volume":"34","author":"Hu","year":"2011"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-012-0451-9","article-title":"Effects of insulin glargine versus metformin on glycemic variability, microvascular and beta-cell function in early type 2 diabetes","volume":"50","author":"Pistrosch","year":"2013","journal-title":"Acta Diabetologica"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-01468","article-title":"Predictors of long-term glycemic remission after 2-week intensive insulin treatment in newly diagnosed type 2 diabetes","volume":"104","author":"Wang","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B43","doi-asserted-by":"publisher","first-page":"4514","DOI":"10.1038\/s41467-023-40287-w","article-title":"Determinants of sustained stabilization of beta-cell function following short-term insulin therapy in type 2 diabetes","volume":"14","author":"Retnakaran","year":"2023","journal-title":"Nat Commun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1203858","article-title":"Basal insulin and cardiovascular and other outcomes in dysglycemia","volume":"367","author":"Gerstein","year":"2012","journal-title":"N Engl J Med"},{"key":"B45","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1089\/dia.2011.0123","article-title":"Noninferiority effects on glycemic control and \u03b2-cell function improvement in newly diagnosed type 2 diabetes patients: basal insulin monotherapy versus continuous subcutaneous insulin infusion treatment","volume":"14","author":"Zeng","year":"2012","journal-title":"Diabetes Technol Ther"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2010.25.3.273","article-title":"The effect of early insulin therapy on pancreatic \u03b2-cell function and long-term glycemic control in newly diagnosed type 2 diabetic patients","volume":"25","author":"Chon","year":"2010","journal-title":"Korean J Intern Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13719","article-title":"Relationship between the early initiation of insulin treatment and diabetic complications in patients newly diagnosed with type 2 diabetes mellitus in Korea: a nationwide cohort study","volume":"13","author":"Jeon","year":"2022"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13693","article-title":"Glycaemic goal attainment and hypoglycaemia outcomes in type 2 diabetes patients initiating insulin glargine 300 units\/mL or 100 units\/mL: real\u2010world results from the DELIVER Na\u00efve cohort study","volume":"21","author":"Bailey","year":"2019"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2015.11.011","article-title":"Clinical and economic outcomes associated with the timing of initiation of basal insulin in patients with type 2 diabetes mellitus previously treated with oral antidiabetes drugs","volume":"38","author":"Levin","year":"2016"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-011-0074-5","article-title":"A real-world study of patients with type 2 diabetes initiating basal insulins via disposable pens","volume":"28","author":"Xie","year":"2011"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.12669\/pjms.37.7.4013","article-title":"The effect of short-term intensive insulin therapy in newly-diagnosed type-2 diabetic patients","volume":"37","author":"Karacaer","year":"2021"},{"key":"B52","first-page":"199","article-title":"Second line initiation of insulin compared with DPP-4 inhibitors after metformin monotherapy is associated with increased risk of all-cause mortality, cardiovascular events, and severe hypoglycemia","volume":"123","author":"Nystr\u00f6m","year":"2017"},{"key":"B53","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1002\/jrsm.1411","article-title":"Risk\u2010of\u2010bias VISualization (robvis): an R package and Shiny web app for visualizing risk\u2010of\u2010bias assessments","volume":"12","author":"McGuinness","year":"2021"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.3060-19","article-title":"Influence of timing of insulin initiation on long-term glycemic control in Japanese patients with type 2 diabetes: a retrospective cohort study","volume":"58","author":"Miyazaki","year":"2019"},{"key":"B55","article-title":"Insulin versus an oral antidiabetic agent as add-on therapy in type 2 diabetes after failure of an oral antidiabetic regimen: a meta-analysis","volume":"2","author":"Gamble","year":"2008"},{"key":"B56","article-title":"Trends in insulin use and diabetes control in the US: 1988\u20131994 and 1999\u20132012","volume":"39","author":"Selvin","year":"2016"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-2441","article-title":"Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes","volume":"38","author":"Inzucchi","year":"2015","journal-title":"Diabetes Care"},{"key":"B58","doi-asserted-by":"publisher","first-page":"S83","DOI":"10.2337\/dc22-S006","article-title":"6. glycemic targets: standards of medical care in diabetes-2022","volume":"45","year":"2022","journal-title":"Diabetes Care"},{"key":"B59","doi-asserted-by":"crossref","DOI":"10.1007\/978-94-007-6686-0_17","article-title":"Clinical approaches to preserving \u03b2-cell function in diabetes","volume-title":"Islets of Langerhans, Second Edition","author":"Wajchenberg","year":"2015"},{"key":"B60","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.ihj.2021.12.004","article-title":"Short-and long-term cardiovascular outcomes in insulin-treated versus non-insulin-treated diabetes mellitus patients after percutaneous coronary intervention: a systematic review and meta-analysis","volume":"74","author":"Hassan","year":"2022"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2022.03.007","article-title":"Effects of insulin on cardiovascular events and all-cause mortality in patients with type 2 diabetes: a meta-analysis of randomized controlled trials","volume":"32","author":"Mannucci","year":"2022"},{"key":"B62","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/s2213-8587(16)30316-3","article-title":"Association of insulin dosage with mortality or major adverse cardiovascular events: a retrospective cohort study","volume":"5","author":"Gamble","year":"2017"},{"key":"B63","article-title":"Cardiovascular safety of glucose\u2010lowering agents as add\u2010on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register","volume":"18","author":"Ekstr\u00f6m","year":"2016"},{"key":"B64","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/s41392-024-01854-9","article-title":"Real-world effectiveness of early insulin therapy on the incidence of cardiovascular events in newly diagnosed type 2 diabetes","volume":"9","author":"Luo","year":"2024"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2020-001194","article-title":"Hypoglycemia in patient with type 2 diabetes treated with insulin: it can happen","volume":"8","author":"Heller","year":"2020"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13009","article-title":"Insulin\u2010associated weight gain in obese type 2 diabetes mellitus patients: what can be done","volume":"19","author":"Brown","year":"2017","journal-title":"Diabetes Obes Metab"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2015.01.030","article-title":"Four-year evolution of insulin regimens, glycaemic control, hypoglycaemia and body weight after starting insulin therapy in type 2 diabetes across three continents","volume":"108","author":"Home","year":"2015"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1080\/00325481.2019.1578590","article-title":"Management of hypoglycemia in older adults with type 2 diabetes","volume":"131","author":"Freeman","year":"2019"},{"key":"B69","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1186\/s12933-023-02056-3","article-title":"Diabetic microvascular disease in non-classical beds: the hidden impact beyond the retina, the kidney, and the peripheral nerves","volume":"22","author":"Mauricio","year":"2023"},{"key":"B70","article-title":"Psychological barriers to insulin use among Australians with type 2 diabetes and clinical strategies to reduce them","volume":"2","author":"Holmes-Truscott","year":"2017"},{"key":"B71","doi-asserted-by":"crossref","DOI":"10.4324\/9781003260219","volume-title":"Psychology in Diabetes Care and Practice","author":"Wilson","year":"2022"},{"key":"B72","doi-asserted-by":"publisher","first-page":"39","DOI":"10.29309\/tpmj\/2016.23.02.858","article-title":"Barriers to the early initiation of insulin therapy among diabetic patients coming to diabetic clinics of tertiary care hospitals","volume":"35","author":"Arshad","year":"2019"},{"key":"B73","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s13300-020-00764-7","article-title":"A practitioner\u2019s toolkit for insulin motivation in adults with type 1 and type 2 diabetes mellitus: evidence-based recommendations from an international expert panel","volume":"11","author":"Kalra","year":"2020"},{"key":"B74","article-title":"Monitoring technologies\u2014continuous glucose monitoring, mobile technology, biomarkers of glycemic control","author":"Reddy","year":"2023"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2023-003930","article-title":"Clinical perspectives on the frequency of hypoglycemia in treat-to-target randomized controlled trials comparing basal insulin analogs in type 2 diabetes: a narrative review","volume":"12","author":"Rosenstock","year":"2024"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1843227\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:28:47Z","timestamp":1788150527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1843227\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":75,"alternative-id":["10.3389\/fendo.2026.1843227"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1843227","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"article-number":"1843227"}}