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Dipeptidyl peptidase\u20104 (DPP\u20104) serves as a target for its treatment, with its inhibitors effectively preserving the levels of glucose\u2010dependent insulinotropic peptide and glucagon\u2010like peptide 1(GLP\u20101). This review presents an overview of the therapeutic possibilities of six frequently employed DPP\u20104 inhibitors (DPP\u20104is) (Sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin and teneligliptin) in managing T2DM, focussing on their characteristics, mechanism of action, advantages and side effects in comparison with alternative oral antidiabetic drugs as well as the possibility of using\n                      <jats:italic>in silico<\/jats:italic>\n                      method in advancing its timely and cost\u2010effective production.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A literature search was conducted using the major search engines such as PubMed\/Medline, Scopus, and Google Scholar, etc. employing terms like \u2018Type 2 diabetes mellitus (T2DM), DPP\u20104 inhibitors, and Dipeptidyl peptidase\u20104\u2019, etc. to identify relevant studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our findings indicate that DPP\u20104is stimulate secretion of insulin and suppress secretion of glucagon by elevating endogenous GLP\u20101 concentrations without an intrinsic hypoglycaemia risk. Although these agents share a common mechanism of action, their considerable structural heterogeneity may lead to distinct pharmacological characteristics. Literature shows that DPP\u20104is have a promising safety profile in comparison with other oral antidiabetic medications, however, certain safety aspects require additional exploration. Different DPP\u20104is have demonstrated comparable safety and tolerability, whether used alone or in combination with other antidiabetic medications. Besides, it has been shown that\n                      <jats:italic>in silico<\/jats:italic>\n                      method could be employed in development of DPP\u20104is. Further research is necessary to ascertain whether differences among DPP\u20104 inhibitors might influence the occurrence of specific adverse effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DPP\u20104 inhibitors remain effective and well\u2010tolerated options for managing T2DM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70277","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:37:49Z","timestamp":1765186669000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Dipeptidyl Peptidase 4 Inhibitors: Novel Therapeutic Agents in the Management of Type\n                    <scp>II<\/scp>\n                    Diabetes Mellitus"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8929-6754","authenticated-orcid":false,"given":"Chinyere","family":"Aloke","sequence":"first","affiliation":[{"name":"Protein Structure\u2010Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science University of the Witwatersrand  Johannesburg South Africa"},{"name":"Department of Medical Biochemistry Alex Ekwueme Federal University Ndufu\u2010Alike  Abakaliki Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwasola Abayomi","family":"Adelusi","sequence":"additional","affiliation":[{"name":"Biotechnology and Food Department University of Johannesburg  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olalekan Olugbenga","family":"Onisuru","sequence":"additional","affiliation":[{"name":"Protein Structure\u2010Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel Amarachi","family":"Iwuchukwu","sequence":"additional","affiliation":[{"name":"Protein Structure\u2010Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikechukwu","family":"Achilonu","sequence":"additional","affiliation":[{"name":"Protein Structure\u2010Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101797\u20108"},{"key":"e_1_2_18_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176275"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.2991\/jegh.k.191028.001"},{"key":"e_1_2_18_5_1","doi-asserted-by":"publisher","DOI":"10.2991\/j.jegh.2017.11.004"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.5.1047"},{"key":"e_1_2_18_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc10\u20100666"},{"key":"e_1_2_18_8_1","doi-asserted-by":"publisher","DOI":"10.5152\/eurjrheum.2018.18044"},{"key":"e_1_2_18_9_1","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v6.i13.1246"},{"key":"e_1_2_18_10_1","doi-asserted-by":"publisher","DOI":"10.17712\/nsj.2018.2.20170132"},{"key":"e_1_2_18_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/20786204.2013.10874407"},{"key":"e_1_2_18_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20101241.2006.01178.x"},{"key":"e_1_2_18_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/713609354"},{"key":"e_1_2_18_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8101391"},{"key":"e_1_2_18_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2228"},{"key":"e_1_2_18_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12328"},{"key":"e_1_2_18_17_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.4.1.3"},{"key":"e_1_2_18_18_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP12303.RA"},{"key":"e_1_2_18_19_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2013.824966"},{"key":"e_1_2_18_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2011\u20101052"},{"key":"e_1_2_18_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11886\u2010013\u20100382\u20102"},{"key":"e_1_2_18_22_1","doi-asserted-by":"publisher","DOI":"10.3810\/pgm.2013.05.2659"},{"key":"e_1_2_18_23_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP12306.RA"},{"key":"e_1_2_18_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1314078"},{"key":"e_1_2_18_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0631828100"},{"key":"e_1_2_18_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120069197"},{"key":"e_1_2_18_27_1","doi-asserted-by":"crossref","unstructured":"D.Somda S. 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