{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:07:07Z","timestamp":1790741227877,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To compare contemporary initial glucose\u2010lowering strategies in adults with type 2 diabetes who were treatment\u2010na\u00efve or had completed adequate washout.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We searched MEDLINE, Embase and the Cochrane Library from inception to 20 September 2025 for randomized trials comparing sodium\u2010glucose cotransporter 2 inhibitor (SGLT2i) monotherapy, glucagon\u2010like peptide\u20101 receptor agonist (GLP\u20101 RA) or dual incretin agonist monotherapy, SGLT2i plus metformin or placebo. Two reviewers independently selected studies and verified extracted data. Bayesian random\u2010effects network meta\u2010analysis was used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty randomized trials with 8947 participants were included; all were at low risk of bias. Compared with placebo, SGLT2i plus metformin produced the largest HbA1c reduction (mean difference [MD] \u20131.36%, 95% credible interval [CrI] \u20131.91 to \u22120.82), followed by GLP\u20101 RA or dual incretin agonist monotherapy (MD \u20131.25%, 95% CrI \u20131.68 to \u22120.83) and SGLT2i monotherapy (MD \u20130.76%, 95% CrI \u20131.10 to \u22120.41). Achievement of HbA1c &lt;\u20097% and fasting plasma glucose reduction showed a similar pattern. GLP\u20101 RA or dual incretin agonist monotherapy produced the greatest body weight percentage reduction (MD \u20134.74%, 95% CrI \u20136.71 to \u22122.90). Active\u2010treatment comparisons were indirect, and baseline HbA1c was higher in the SGLT2i plus metformin node. Certainty of evidence was low or very low across key comparisons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SGLT2i plus metformin and GLP\u20101 RA or dual incretin agonist therapy are both reasonable contemporary initial glucose\u2010lowering strategies for type 2 diabetes. Selection between these strategies should take into consideration phenotype, treatment priorities, tolerability, cost, access and patient preference.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>PROSPERO: CRD420251178714<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71397","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:52:11Z","timestamp":1790740331000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Contemporary Initial Glucose\u2010Lowering Strategies for Type 2 Diabetes: A Systematic Review and Bayesian Network Meta\u2010Analysis"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7398-9070","authenticated-orcid":false,"given":"Gabriel","family":"Cavalcante Lima Chagas","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayara","family":"Rios Leite Macedo Monteiro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Texas Health Resources  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Loch","family":"Eira","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina de Mar\u00edlia  Mar\u00edlia S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaspar R.","family":"Chiappa","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Universidad Aut\u00f3noma de Chile  Providencia Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Joaquim Silva","family":"Cust\u00f3dio","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Bahia Universidade Federal da Bahia  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5996-0661","authenticated-orcid":false,"given":"Marconi","family":"Abreu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology University of Texas Southwestern  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc26\u2010S009"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010022\u201005787\u20102"},{"key":"e_1_2_10_4_1","unstructured":"National Institute for Health and Care Excellence \u201cType 2 Diabetes in Adults: Management \u201d NICE Guideline NG28 February 2026. London: National Institute for Health and Care Excellence https:\/\/www.nice.org.uk\/guidance\/ng28\/chapter\/Initial\u2010medicines."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2026.01.006"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(24)00271\u20107"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2313917"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8010045"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2200433"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_10_11_1","unstructured":"G. C. L.Chagas M. R. L. M.Monteiro M. L.Eira et\u00a0al. \u201cFirst\u2010Line Treatment Strategies for Drug\u2010Naive Type 2 Diabetes: A Network Meta\u2010Analysis of SGLT2 Inhibitors GLP\u20101 RAs and SGLT2i Plus Metformin \u201dPROSPERO 2025 CRD420251178714 https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251178714."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.7326\/ANNALS\u201025\u201000739"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.07.015"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003082"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc19\u20100749"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463\u20101326.2012.01659.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc10\u20100612"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16\u20100522"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20101241.2012.02911.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2013.11.002"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14969"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13098\u2010021\u201000649\u20100"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2008.08.006"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(13)70084\u20106"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010015\u20100314\u20100"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15\u20101736"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2505669"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(17)30013\u2010X"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12393"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12391"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanwpc.2024.101101"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)01324\u20106"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13107"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0806470"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17\u20101144"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464\u20105491.2007.02043.x"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2022.04.002"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.04.031"},{"key":"e_1_2_10_40_1","unstructured":"Eli Lilly and Company \u201cLilly's Triple Agonist Retatrutide Demonstrated Significant Reductions in A1C and Weight in First Phase 3 Trial for Treatment of Type 2 Diabetes \u201dMarch 19 2026 https:\/\/investor.lilly.com\/news\u2010releases\/news\u2010release\u2010details\/lillys\u2010triple\u2010agonist\u2010retatrutide\u2010demonstrated\u2010significant."}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.71397","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.71397","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.71397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:52:13Z","timestamp":1790740333000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/10.1111\/dom.71397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":39,"alternative-id":["10.1111\/dom.71397"],"URL":"https:\/\/doi.org\/10.1111\/dom.71397","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"2026-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"dom.71397"}}