{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:45:57Z","timestamp":1768459557434,"version":"3.49.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T00:00:00Z","timestamp":1664841600000},"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><jats:title>Background<\/jats:title><jats:p>In contrast to Western population, glucagon-like peptide-1 (GLP-1) levels are preserved in some East Asian population with type 2 diabetes (T2D), explaining why dipeptidyl peptidase-IV (DPP-IV) inhibitors are more effective in East Asians. We assessed whether differences in endogenous GLP-1 levels resulted in different treatment responses to DPP-IV inhibitors in prediabetes and T2D.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective 12-week study using linagliptin 5mg once daily in 50 subjects (28 prediabetes and 22 T2D) who were stratified into high versus low fasting GLP-1 groups. A 75-g oral glucose tolerance test (OGTT) was performed at week 0 and 12. Primary outcomes were changes in HbA1c, fasting and post-OGTT glucose after 12 weeks. Secondary outcomes included changes in insulin resistance and beta cell function indices.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was a greater HbA1c reduction in subjects with high GLP-1 compared to low GLP-1 levels in both the prediabetes and T2D populations [least-squares mean (LS-mean) change of -0.33% vs. -0.11% and -1.48% vs. -0.90% respectively)]. Linagliptin significantly reduced glucose excursion by 18% in high GLP-1 compared with 8% in low GLP-1 prediabetes groups. The reduction in glucose excursion was greater in high GLP-1 compared to low GLP-1 T2D by 30% and 21% respectively. There were significant LS-mean between-group differences in fasting glucose (-0.95 mmol\/L), 2-hour glucose post-OGTT (-2.4 mmol\/L) in the high GLP-1 T2D group. Improvement in insulin resistance indices were seen in the high GLP-1 T2D group while high GLP-1 prediabetes group demonstrated improvement in beta cell function indices. No incidence of hypoglycemia was reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Linagliptin resulted in a greater HbA1c reduction in the high GLP-1 prediabetes and T2D compared to low GLP-1 groups. Endogenous GLP-1 level play an important role in determining the efficacy of DPP-IV inhibitors irrespective of the abnormal glucose tolerance states.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.1012412","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T04:52:30Z","timestamp":1664859150000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Endogenous GLP-1 levels play an important role in determining the efficacy of DPP-IV Inhibitors in both prediabetes and type 2 diabetes"],"prefix":"10.3389","volume":"13","author":[{"given":"Shiau Chin","family":"Chong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norlela","family":"Sukor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah Anne","family":"Robert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim Fong","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nor Azmi","family":"Kamaruddin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00260","article-title":"From the incretin concept and the discovery of glp-1 to today's diabetes therapy","volume":"10","author":"Holst","year":"2019","journal-title":"Front Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-018-1222-z","article-title":"The efficacy and safety of dipeptidyl peptidase-4 inhibitors for type 2 diabetes: A Bayesian network meta-analysis of 58 randomized controlled trials","volume":"56","author":"Ling","year":"2019","journal-title":"Acta Diabetol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1111\/j.1463-1326.2012.01586.x","article-title":"The effect of linagliptin on glycaemic control and tolerability in patients with type 2 diabetes mellitus: A systematic review and meta-analysis","volume":"14","author":"Singh-Franco","year":"2012","journal-title":"Diabetes Obes Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2019.154054","article-title":"The combination of linagliptin, metformin and lifestyle modification to prevent type 2 diabetes (Prellim)","volume":"104","author":"Guardado-Mendoza","year":"2020","journal-title":"A Randomized Clin Trial. Metab Clin Exp"},{"key":"B5","doi-asserted-by":"publisher","first-page":"8750","DOI":"10.1038\/s41598-021-88108-8","article-title":"Effect of linagliptin on glucose metabolism and pancreatic beta cell function in patients with persistent prediabetes after metformin and lifestyle","volume":"11","author":"Alvarez-Canales","year":"2021","journal-title":"Sci Rep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1007\/s11892-015-0602-9","article-title":"\u03b2 cell dysfunction versus insulin resistance in the pathogenesis of type 2 diabetes in East asians","volume":"15","author":"Yabe","year":"2015","journal-title":"Curr Diabetes Rep"},{"key":"B7","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1007\/s00125-012-2827-3","article-title":"Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between asians and non-asians: A systematic review and meta-analysis","volume":"56","author":"Kim","year":"2013","journal-title":"Diabetologia"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1R041","article-title":"Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes: Meta-analysis","volume":"46","author":"Park","year":"2012","journal-title":"Ann Pharmacother"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-2419","article-title":"Efficacy of modern diabetes treatments dpp-4i, sglt-2i, and glp-1ra in white and Asian patients with diabetes: A systematic review and meta-analysis of randomized controlled trials","volume":"43","author":"Gan","year":"2020","journal-title":"Diabetes Care"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.692","article-title":"Ethnic difference in the pharmacodynamics-efficacy relationship of dipeptidyl peptidase-4 inhibitors between Japanese and non-Japanese patients: A systematic review","volume":"102","author":"Ito","year":"2017","journal-title":"Clin Pharmacol Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2011.03387.x","article-title":"Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: A 24-week randomized study","volume":"28","author":"Owens","year":"2011","journal-title":"Diabetes Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2010.01350.x","article-title":"Effect of linagliptin monotherapy on glycaemic control and markers of \u03b2-cell function in patients with inadequately controlled type 2 diabetes: A randomized controlled trial","volume":"13","author":"Del Prato","year":"2011","journal-title":"Diabetes Obes Metab"},{"key":"B13","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/j.1463-1326.2010.01326.x","article-title":"Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled study","volume":"13","author":"Taskinen","year":"2011","journal-title":"Diabetes Obes Metab"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.8.7750","article-title":"Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients","volume":"86","author":"Toft-Nielsen","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2010.06.004","article-title":"Incretin secretion and serum dpp-iv activity in Korean patients with type 2 diabetes","volume":"89","author":"Han","year":"2010","journal-title":"Diabetes Res Clin Pract"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S220180","article-title":"Predictors of the efficacy of dipeptidyl peptidase-4 inhibitors in Taiwanese patients with type 2 diabetes mellitus","volume":"12","author":"Lin","year":"2019","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.1184","article-title":"Predictors of response to dipeptidyl peptidase-4 inhibitors: Evidence from randomized clinical trials","volume":"27","author":"Monami","year":"2011","journal-title":"Diabetes Metab Res Rev"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2015.39.4.342","article-title":"Predictive factors for efficacy of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus","volume":"39","author":"Yagi","year":"2015","journal-title":"Diabetes Metab J"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0805","article-title":"Effects of sitagliptin and metformin treatment on incretin hormone and insulin secretory responses to oral and \u201cIsoglycemic\u201d intravenous glucose","volume":"63","author":"Vardarli","year":"2014","journal-title":"Diabetes"},{"key":"B20","doi-asserted-by":"crossref","DOI":"10.1210\/jc.2006-1882","article-title":"The dipeptidyl peptidase iv inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients","volume":"92","author":"Balas","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-S002","article-title":"Classification and diagnosis of diabetes: Standards of medical care in diabetes\u20132020","volume":"43","year":"2019","journal-title":"Diabetes Care"},{"key":"B22","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin Chem"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.24.4.775","article-title":"Postprandial blood glucose","volume":"24","year":"2001","journal-title":"Diabetes Care"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2018.09.010","article-title":"Triglycerides and glucose index as an insulin resistance marker in a sample of healthy adults","volume":"13","author":"Toro-Huamanchumo","year":"2019","journal-title":"Diabetes Metab Syndr"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031374","article-title":"Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment are useful indexes of insulin resistance in type 2 diabetic patients with wide range of fasting plasma glucose","volume":"89","author":"Yokoyama","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/jch.14155","article-title":"Assessment of preferred methods to measure insulin resistance in Asian patients with hypertension","volume":"23","author":"Minh","year":"2021","journal-title":"J Clin Hypertens (Greenwich)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.diabres.2005.10.005","article-title":"Insulinogenic indices from insulin and c-peptide: Comparison of beta-cell function from ogtt and ivgtt","volume":"72","author":"Tura","year":"2006","journal-title":"Diabetes Res Clin Pract"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2009.02841.x","article-title":"Evaluation of proposed oral disposition index measures in relation to the actual disposition index","volume":"26","author":"Retnakaran","year":"2009","journal-title":"Diabetes Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.961432","article-title":"Fasting and Stimulated Glucagon-Like Peptide-1 Exhibit a Compensatory Adaptive Response in Diabetes and Pre-Diabetes States: A Multi-Ethnic Comparative Study","volume":"13","author":"Chong","year":"2022","journal-title":"Frontiers in Endocrinology"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1705-7","article-title":"Glucagon-like peptide-1 mediates the therapeutic actions of dpp-iv inhibitors","volume":"48","author":"Holst","year":"2005","journal-title":"Diabetologia"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00482-9","article-title":"The incretin effect in healthy individuals and those with type 2 diabetes: Physiology, pathophysiology, and response to therapeutic interventions","volume":"4","author":"Nauck","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1720355","article-title":"Preservation of active incretin hormones by inhibition of dipeptidyl peptidase iv suppresses meal-induced incretin secretion in dogs","volume":"172","author":"Deacon","year":"2002","journal-title":"J Endocrinol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-2841-0","article-title":"Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: Systematic review and meta-analyses of clinical studies","volume":"56","author":"Calanna","year":"2013","journal-title":"Diabetologia"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.146861","article-title":"Incretin response in Asian type 2 diabetes: Are indians different","volume":"19","author":"Singh","year":"2015","journal-title":"Indian J Endocrinol Metab"},{"key":"B36","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1111\/jdi.12305","article-title":"Incretin physiology and pathophysiology from an Asian perspective","volume":"6","author":"Cho","year":"2015","journal-title":"J Diabetes Investig"},{"key":"B37","first-page":"57","article-title":"Why are incretin-based therapies more efficient in East asians? perspectives from the pathophysiology of type 2 diabetes and East Asian dietary habits","volume":"3","author":"Daisuke Yabe","year":"2015","journal-title":"Eur Med J"},{"key":"B38","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.numecd.2021.11.017","article-title":"Comparison of triglyceride-glucose index and homa-ir for predicting prevalence and incidence of metabolic syndrome","volume":"32","author":"Son","year":"2022","journal-title":"Nutr Metab Carbiovasc Dis"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109042","article-title":"The triglyceride\u2013glucose index is a more powerful surrogate marker for predicting the prevalence and incidence of type 2 diabetes mellitus than the homeostatic model assessment of insulin resistance","volume":"180","author":"Park","year":"2021","journal-title":"Diabetes Res Clin Pract"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01473.x","article-title":"Dipeptidyl peptidase-4 inhibitors and preservation of pancreatic islet-cell function: A critical appraisal of the evidence","volume":"14","author":"van Genugten","year":"2012","journal-title":"Diabetes Obes Metab"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-017-0595-7","article-title":"Efficacy and safety of linagliptin in 2681 Asian patients stratified by age, obesity, and renal function: A pooled analysis of randomized clinical trials","volume":"34","author":"Ning","year":"2017","journal-title":"Adv Ther"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1012412\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T04:52:35Z","timestamp":1664859155000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1012412\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,4]]},"references-count":41,"alternative-id":["10.3389\/fendo.2022.1012412"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.1012412","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,4]]},"article-number":"1012412"}}