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We have proposed that diabetes in MIDD arises from a combination of insulin resistance and impaired \u03b2\u2010cell function that is more likely to occur in the presence of high skeletal muscle heteroplasmy and moderate \u03b2\u2010cell heteroplasmy for m.3243A&gt;G and to be driven by oxidative stress as a major pathophysiologic mechanism. There are no randomised trials specifically on the management of MIDD. An approach to MIDD informed by its pathophysiology could optimise management and be a framework for future trials. In this narrative review, we discuss the effects of existing anti\u2010hyperglycaemic medications on oxidative stress, mitochondrial function, and cardiorenal protection. We also review the published case reports and series on the management of diabetes associated with MIDD, and the safety of insulin and non\u2010insulin medications in MIDD. We found that glucagon\u2010like peptide\u20101 receptor agonists and sodium\u2010glucose cotransporter\u20102 inhibitors have favourable properties in addressing oxidative stress and mitochondrial function. They also harbour cardiorenal protection properties independent from their effect on glucose control that are fully relevant in MIDD, making them ideal candidates as first\u2010line agents for the management of MIDD. Accordingly, we share our perspective on a disease\u2010specific algorithm for the management of MIDD diabetes that could delay or prevent the development of cardiovascular and renal complications associated with this mitochondrial disease.\n                  <\/jats:p>","DOI":"10.1111\/dom.70240","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:22:09Z","timestamp":1761657729000},"page":"826-839","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Diabetes management in maternally inherited diabetes and deafness (\n                    <scp>MIDD<\/scp>\n                    ): A review and a proposed treatment algorithm"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0136-4869","authenticated-orcid":false,"given":"Ahsen","family":"Chaudhry","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Medicine Clinician Investigator Program University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-2356","authenticated-orcid":false,"given":"David M.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine Clinician Investigator Program University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-2064","authenticated-orcid":false,"given":"Jean\u2010Pierre","family":"Chanoine","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Pediatrics British Columbia Children's Hospital and University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.728043"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/db24-0515"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11050801"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.3.729"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0301-9"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2020.09.013"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-024-00556-1"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab036"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2020.107584"},{"key":"e_1_2_12_11_1","unstructured":"SchaeferAM WalkerM NgYS GormanGS McFarlandR TurnbullDM.Newcastle mitochondrial disease guidelines: diabetes mellitus in adult mitochondrial disease: screening and initial management. 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