Efficacy and Safety of Non-Insulin Antidiabetic Drugs in Cats: A Systematic Review

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–benefit 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.