{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T09:52:31Z","timestamp":1768038751093,"version":"3.49.0"},"reference-count":73,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006462","name":"City University of New York","doi-asserted-by":"crossref","award":["#68333-00 56"],"award-info":[{"award-number":["#68333-00 56"]}],"id":[{"id":"10.13039\/100006462","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Depression and diabetic neuropathy (DN) commonly complicate diabetes and impair glycemic control and quality of life. Ketamine and its S-enantiomer, esketamine, provide rapid antidepressant and analgesic effects, yet diabetes-related pathophysiology and co-therapies may modify exposure, response, and safety. Methods: We conducted a scoping review following PRISMA-ScR. MEDLINE\/PubMed, CINAHL, and APA PsycInfo were searched (January 2020\u201331 May 2025). Eligible human and animal studies evaluated ketamine, esketamine, or norketamine in the context of diabetes (type 1 [T1DM], type 2 [T2DM], gestational [GDM]), or DN, and reported psychiatric, analgesic, metabolic, or mechanistic outcomes. Two reviewers independently screened and charted data; no formal risk-of-bias assessment was performed. Results: Eleven studies met inclusion criteria: four human case reports\/series (three T1DM, one T2DM), one randomized trial in GDM, two narrative reviews of topical ketamine for DN, and four preclinical rodent studies using streptozotocin- or diet-induced diabetes models. Short-term improvements were reported for treatment-resistant depression and neuropathic pain, including opioid-sparing postoperative analgesia in GDM. Glycemic effects varied across settings, with both hyperglycemia and hypoglycemia reported. Mechanistic and clinical drug\u2013drug and drug-disease interactions (particularly involving metformin, GLP-1 receptor agonists, SGLT2 inhibitors, and CYP3A4\/CYP2B6 modulators) remain insufficiently studied. We outline a forward-looking population pharmacokinetic (popPK) and pharmacokinetic-pharmacodynamic (PK-PD) research agenda, including priority covariates (eGFR, hepatic function, inflammatory status, HbA1c, genotype, co-medications) and sparse-sampling windows for future model-informed precision dosing. Conclusions: Current evidence supports cautious, selective use of ketamine for refractory depression and DN within multidisciplinary diabetes care. Purpose-built popPK\/PK-PD studies in both human and preclinical diabetic models cohorts are needed to quantify variability, define drug\u2013disease\u2013drug interactions and glycemic risk, and inform individualized dosing strategies.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010081","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T11:11:21Z","timestamp":1767870681000},"page":"81","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ketamine in Diabetes Care: Metabolic Insights and Clinical Applications"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7314-5487","authenticated-orcid":false,"given":"Shiryn D.","family":"Sukhram","sequence":"first","affiliation":[{"name":"Department of Biology, College of Staten Island, New York, NY 10314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majandra","family":"Sanchez","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Long Island University, New York, NY 11201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayotunde","family":"Anidugbe","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Long Island University, New York, NY 11201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bora","family":"Kupa","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Staten Island, New York, NY 10314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5676-6669","authenticated-orcid":false,"given":"Vincent P.","family":"Edwards","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences, Seton Hall University, South Orange, NJ 07079, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0762-4118","authenticated-orcid":false,"given":"Muhammad","family":"Zia","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Staten Island, New York, NY 10314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grozdena","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Staten Island, New York, NY 10314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2013). 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