{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:18:42Z","timestamp":1788153522505,"version":"build-2803163510"},"reference-count":31,"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>Background<\/jats:title>\n                    <jats:p>Obesity and type 2 diabetes mellitus (T2DM) are closely linked through shared pathophysiological mechanisms affecting glucose metabolism and insulin resistance. Sodium\u2013glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely recommended for patients with T2DM who are overweight or obese because of their favorable effects. However, whether baseline obesity influences the glycemic response to these agents in real-world clinical practice remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter retrospective study included adults with T2DM initiated on either SGLT2i or GLP-1RA at three healthcare centers in Riyadh, Saudi Arabia. Patients were stratified into obese (BMI \u226530 kg\/m\u00b2) and non-obese (BMI &amp;lt;30 kg\/m\u00b2). Changes in HbA1c, body weight, and BMI were evaluated at 3, 6, 9, and 12 months. Between-group comparisons were performed using independent t-tests, followed by mixed-effects models for repeated measures (MMRM) to adjust for potential confounders. Secondary outcomes included the proportions of patients achieving \u22655% weight loss, HbA1c &amp;lt;7.0% (among those uncontrolled at baseline), and HbA1c reductions of \u22650.5% and \u22651.0%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 1,016 patients were included, of whom 73.4% were obese. Obese patients were associated with greater reductions in absolute body weight and BMI at 3, 6, 9, and 12 months than non-obese patients, although their higher baseline body weight may have contributed to these differences. Responder analysis showed that obesity was associated with a higher likelihood of achieving \u22655% weight loss at months 3 (21.9% vs. 12.0%, p=0.0016) and 6 (27.2% vs. 15.5%, p=0.0086). In the adjusted MMRM, obesity was associated with greater least-squares mean reductions in weight and BMI (p&amp;lt;0.05), whereas HbA1c reductions and responder rates (HbA1c &amp;lt;7.0%, \u22650.5%, and \u22651.0% reductions) were statistically comparable between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that baseline obesity was associated with greater reductions in anthropometric measures following SGLT2i or GLP-1RA therapy after multivariable adjustment, whereas improvements in glycemic control were similar between obese and non-obese patients. As these findings are hypothesis-generating, prospective studies are needed to determine whether baseline BMI modifies treatment response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1847755","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:29:07Z","timestamp":1788150547000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative change in HbA1c and weight outcomes between obese and non-obese adults with type 2 diabetes mellitus treated with SGLT-2 inhibitors or GLP-1 receptor agonists"],"prefix":"10.3389","volume":"17","author":[{"given":"Omar A.","family":"Almohammed","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, King Saud University","place":["Riyadh, Saudi Arabia"]},{"name":"Pharmacoeconomics Research Unit, College of Pharmacy, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar A.","family":"Alshaya","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences","place":["Riyadh, Saudi Arabia"]},{"name":"King Abdullah International Medical Research Center","place":["Riyadh, Saudi Arabia"]},{"name":"Pharmaceutical Care Department, Ministry of National Guard-Health Affairs","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lama A.","family":"Alduhayshi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara T.","family":"Alshaibani","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meshal S.","family":"Alhamed","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"Alzeer","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Othman M.","family":"Alabdullah","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed F.","family":"Ibn Saqyan","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majed S.","family":"Al Yami","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences","place":["Riyadh, Saudi Arabia"]},{"name":"King Abdullah International Medical Research Center","place":["Riyadh, Saudi Arabia"]},{"name":"Pharmaceutical Care Department, Ministry of National Guard-Health Affairs","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"Bin Sheraim","sequence":"additional","affiliation":[{"name":"Pharmaceutical Care Services, King Abdullah Bin Abdulaziz University Hospital","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaya N.","family":"Almohareb","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences","place":["Riyadh, Saudi Arabia"]},{"name":"King Abdullah International Medical Research Center","place":["Riyadh, Saudi Arabia"]},{"name":"Pharmaceutical Care Department, Ministry of National Guard-Health Affairs","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamah M.","family":"Alfayez","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, Qassim University","place":["Qassim, Buraydah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazwa B.","family":"Korayem","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cmet.2021.12.012","article-title":"Why does obesity cause diabetes","volume":"34","author":"Klein","year":"2022","journal-title":"Cell Metab"},{"key":"B2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cmet.2017.04.011","article-title":"Sodium-glucose co-transporters and their inhibition: Clinical physiology","volume":"26","author":"Ferrannini","year":"2017","journal-title":"Cell Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.34067\/kid.0002772021","article-title":"SGLT2 inhibitors: Physiology and pharmacology","volume":"2","author":"Wright","year":"2021","journal-title":"Kidney360"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-1057-0","article-title":"Emerging role of SGLT-2 inhibitors for the treatment of obesity","volume":"79","author":"Pereira","year":"2019","journal-title":"Drugs"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2337\/dc26-s009","article-title":"Pharmacologic approaches to glycemic treatment: Standards of care in diabetes-2026","volume":"49","year":"2026","journal-title":"Diabetes Care"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2337\/figshare.20800537","article-title":"Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"65","author":"Davies","year":"2022","journal-title":"Diabetologia"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0278685","article-title":"Effect of glucagon-like peptide-1 receptor agonists on glycemic control, and weight reduction in adults: A multivariate meta-analysis","volume":"18","author":"Yeh","year":"2023","journal-title":"PLoS One"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000040364","article-title":"Effect of GLP-1 receptor agonists on weight and cardiovascular outcomes: A review","volume":"103","author":"Raza","year":"2024","journal-title":"Med (Baltimore)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-061807","article-title":"Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight\/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis","volume":"13","author":"Ma","year":"2023","journal-title":"BMJ Open"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12625","article-title":"Comparisons of weight changes between sodium-glucose cotransporter 2 inhibitors treatment and glucagon-like peptide-1 analogs treatment in type 2 diabetes patients: A meta-analysis","volume":"8","author":"Cai","year":"2017","journal-title":"J Diabetes Investig"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-022-01217-z","article-title":"Liraglutide improved cardiometabolic parameters more in obese than in non-obese patients with type 2 diabetes: A real-world 18-month prospective study","volume":"13","author":"Nikolic","year":"2022","journal-title":"Diabetes Ther"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnesp.2024.07.016","article-title":"Effect of sodium glucose co-transporter 2 inhibitor use on anthropometric measurements and blood glucose in obese and non-obese type 2 diabetic patients","volume":"63","author":"Dedemen","year":"2024","journal-title":"Clin Nutr ESPEN"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12617","article-title":"Improvement in glycated haemoglobin evaluated by baseline body mass index: a meta-analysis of the liraglutide phase III clinical trial programme","volume":"18","author":"Montanya","year":"2016","journal-title":"Diabetes Obes Metab"},{"key":"B14","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1056\/nejmoa2032183","article-title":"Once-weekly semaglutide in adults with overweight or obesity","volume":"384","author":"Wilding","year":"2021","journal-title":"N Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1504720","article-title":"Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N Engl J Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2337\/db25-758-p","article-title":"758-P: Titration to maintenance doses of GLP-1R agonists for overweight and obesity is suboptimal for majority of patients\u2014evidence from a real-world claims dataset","volume":"74","author":"Armstrong","year":"2025","journal-title":"Diabetes"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1603827","article-title":"Liraglutide and cardiovascular outcomes in type 2 diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N Engl J Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1056\/nejmoa1611925","article-title":"Canagliflozin and cardiovascular and renal events in type 2 diabetes","volume":"377","author":"Neal","year":"2017","journal-title":"N Engl J Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1812389","article-title":"Dapagliflozin and cardiovascular outcomes in type 2 diabetes","volume":"380","author":"Wiviott","year":"2019","journal-title":"N Engl J Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1607141","article-title":"Semaglutide and cardiovascular outcomes in patients with type 2 diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N Engl J Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1080\/00325481.2019.1549459","article-title":"Efficacy and renal outcomes of SGLT2 inhibitors in patients with type 2 diabetes and chronic kidney disease","volume":"131","author":"Kelly","year":"2019","journal-title":"Postgrad Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1097\/mnh.0000000000000584","article-title":"Renal effects of SGLT2 inhibitors: an update","volume":"29","author":"Nespoux","year":"2020","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.20835","article-title":"Effects of sodium glucose cotransporter 2 inhibitors by diabetes status and level of albuminuria: A meta-analysis","volume":"335","author":"Staplin","year":"2026","journal-title":"Jama"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00155","article-title":"The discovery and development of liraglutide and semaglutide","volume":"10","author":"Knudsen","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s13300-020-00951-6","article-title":"Sodium-glucose co-transporter 2 (SGLT2) inhibitors: Are they all the same? A narrative review of cardiovascular outcome trials","volume":"12","author":"Williams","year":"2021","journal-title":"Diabetes Ther"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/med.0000000000000311","article-title":"An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus","volume":"24","author":"Hsia","year":"2017","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"B27","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s12325-018-0824-8","article-title":"Body weight considerations in the management of type 2 diabetes","volume":"36","author":"Apovian","year":"2019","journal-title":"Adv Ther"},{"key":"B28","doi-asserted-by":"publisher","first-page":"13438","DOI":"10.3390\/ijms252413438","article-title":"Beyond calories: Individual metabolic and hormonal adaptations driving variability in weight management-a state-of-the-art narrative review","volume":"25","author":"Theodorakis","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/oby.24242","article-title":"Associations between decreases in adiposity and reductions in HbA1c and insulin use in the Look AHEAD cohort","volume":"33","author":"Palmer","year":"2025","journal-title":"Obes (Silver Spring)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2024.102054","article-title":"The prevalence of cardiovascular diseases, chronic kidney disease, and obesity in patients with type 2 diabetes mellitus and the description of concurrent treatments: A two-center retrospective cross-sectional study in Saudi Arabia","volume":"32","author":"Alshaya","year":"2024","journal-title":"Saudi Pharm J"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2337\/dc26-s008","article-title":"8. Obesity and weight management for the prevention and treatment of diabetes: Standards of care in diabetes\u20132026","volume":"49","year":"2025","journal-title":"Diabetes Care"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1847755\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:29:08Z","timestamp":1788150548000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1847755\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":31,"alternative-id":["10.3389\/fendo.2026.1847755"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1847755","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"article-number":"1847755"}}