{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T22:44:19Z","timestamp":1785192259015,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":91,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100014786","name":"Northern Border University","doi-asserted-by":"publisher","award":["NBU-CRP-2026-3770"],"award-info":[{"award-number":["NBU-CRP-2026-3770"]}],"id":[{"id":"10.13039\/501100014786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The management of type 2 diabetes with metformin as the first\u2010line therapy has long been established. However, combination therapy of metformin and other oral antidiabetics became necessary to achieve optimal glycemic targets. Recently, the rising cost of these combinations poses a challenge for the healthcare system and patients, particularly in low\u2010 and middle\u2010income settings, highlighting the need to balance clinical benefits with economic considerations to ensure access to treatment while maintaining sustainability in patient care. This review aims to compare the efficacy, safety, and cost\u2010effectiveness of DPP\u20104 inhibitors with metformin\/metformin with other combinations and metformin alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A literature search was performed through databases including PubMed, Scopus, Cochrane, clinicaltrials.gov, and Google Scholar using specific keywords on \u201ctype 2 diabetes mellitus management,\u201d \u201cmetformin,\u201d \u201cDPP\u20104 inhibitors,\u201d \u201csafety,\u201d and \u201cefficacy.\u201d The retrieved studies were screened and selected according to eligibility criteria, followed by data extraction and critical appraisal. The extracted data were synthesized and reported according to the PRISMA guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty\u2010five eligible studies were included in the review. From the studies, oral antidiabetic options apart from DPP\u20104 inhibitors commonly combined with metformin, either as free or fixed\u2010dose combinations, include SGLT\u20102 inhibitors, sulfonylureas, GLP\u20101 receptor agonists, insulin, and thiazolidinediones (TZDs). The efficacy of this drug combination is comparable to that of metformin monotherapy, which is more cost\u2010effective, especially at the beginning of treatment. Where metformin monotherapy fails, the efficacy of an add\u2010on therapy as a second line depends on the specific target and individual patient differences, and even triple therapy may be recommended for some individuals. The cost\u2010effectiveness of each combination depended on the cost\u2010effectiveness model used in the assessment and the nature of the healthcare setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>DPP\u20104 inhibitors\/metformin demonstrate significant HbA1c reduction, but their low cost\u2010effectiveness hinders patient adherence compared to metformin monotherapy, free drugs, or other combinations. For that, initiating therapy with cost\u2010effective metformin alone is recommended. Manufacturer\u2010funded trials highlight a potential bias, necessitating independent research validations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jdr\/8464330","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T12:54:56Z","timestamp":1775134496000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative Efficacy, Safety, and Cost\u2010Utility of DPP\u20104 Inhibitors and Metformin Combination Therapy in Type 2 Diabetes: A Systematic Review of Real\u2010World Clinical and Economic Outcomes"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7322-9100","authenticated-orcid":false,"given":"Abdulgafar Olayiwola","family":"Jimoh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5765-4580","authenticated-orcid":false,"given":"Shuaibu Abdullahi","family":"Hudu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas Ahmad","family":"Sabir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2377-7045","authenticated-orcid":false,"given":"Adamu Ahmed","family":"Adamu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-8261","authenticated-orcid":false,"given":"Nura","family":"Bello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albashir","family":"Tahir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6955-5092","authenticated-orcid":false,"given":"Nura","family":"Abubakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051770"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v12.i4.344"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0034"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph14020122"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S295459"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/hcs2.89"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.30935\/jconseph\/11276"},{"key":"e_1_2_9_8_2","first-page":"1","article-title":"Pharmacoeconomics and Health Policy: Assessing the Cost-Effectiveness of Pharmaceutical Interventions and Its Insinuations for Policy Decision-Making Strategy","volume":"23","author":"Alaklobi A. 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