{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:42:37Z","timestamp":1760060557643,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Background: While insulin is the standard of care for feline diabetes mellitus (FDM), non-insulin antidiabetic drugs (NIADs) are emerging as alternatives. This systematic review aims to synthesize and critically appraise the current evidence for the efficacy and safety of NIADs in cats. Methods: A systematic review was conducted following PRISMA guidelines. Major databases were searched for studies evaluating NIADs in diabetic cats or at-risk\/experimental models. Risk of bias was assessed using RoB 2 and ROBINS-I tools. Results: Twenty studies were included. In diabetic cats (10 studies), traditional agents (glipizide, metformin, acarbose) showed limited efficacy based on evidence with a high risk of bias. Newer SGLT2 inhibitors (bexagliflozin, velagliflozin) demonstrated high treatment success rates and non-inferiority to insulin but were associated with a significant risk of euglycemic diabetic ketoacidosis (eDKA). In at-risk\/experimental models (10 studies), thiazolidinediones consistently improved insulin sensitivity, while glipizide was shown to accelerate islet amyloidosis. Conclusions: The evidence supports a paradigm shift towards SGLT2 inhibitors as a viable oral monotherapy for select cases of FDM. This alters the clinical risk\u2013benefit discussion from preventing hypoglycemia to mitigating eDKA. Significant evidence gaps remain, particularly the lack of high-quality RCTs and data in cats with common comorbidities.<\/jats:p>","DOI":"10.3390\/ani15172561","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T14:02:46Z","timestamp":1756735366000},"page":"2561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Non-Insulin Antidiabetic Drugs in Cats: A Systematic Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2317-9164","authenticated-orcid":false,"given":"F\u00e9lix","family":"Romero-V\u00e9lez","sequence":"first","affiliation":[{"name":"Hospital Cl\u00ednic Veterinari, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5447-8171","authenticated-orcid":false,"given":"Juan","family":"Rejas","sequence":"additional","affiliation":[{"name":"Department of Animal Medicine, Surgery and Anatomy, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5655-0445","authenticated-orcid":false,"given":"Rafael","family":"Ruiz de Gopegui","sequence":"additional","affiliation":[{"name":"Department of Animal Medicine and Surgery, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.2460\/javma.24.03.0174","article-title":"Velagliflozin, a Once-Daily, Liquid, Oral SGLT2 Inhibitor, Is Effective as a Stand-Alone Therapy for Feline Diabetes Mellitus: The SENSATION Study","volume":"262","author":"Behrend","year":"2024","journal-title":"J. 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