Evaluation of the oral antihyperglycemic drug metformin in normal and diabetic cats.

Metformin is an oral antidiabetic drug that improves control of glycemia primarily by inhibiting hepatic gluconeogenesis and glycogenolysis. This study evaluated the usefulness of metformin for the treatment of diabetes mellitus in cats. The study consisted of 3 phases. Phase I was a dose-finding study performed in healthy cats that were randomly administered varying doses of metformin to determine the approximate dose that would yield plasma concentrations known to be effective in humans. Phase 2 was a 3-week safety study performed in healthy cats to determine if cats could tolerate the daily oral dose and administration protocol identified during phase 1. Phase 3 was a clinical trial evaluating the clinical response of diabetic cats to oral metformin treatment. Five cats with newly diagnosed, naturally acquired diabetes mellitus were enrolled in phase 3. Plasma metformin concentrations in the therapeutic range of 0.5-2 microg/mL were achieved with doses of 50 mg/cat PO q12h without dramatic drug accumulation. Intermittent lethargy, inappetence, vomiting, and weight loss were identified, and the results of the CBC, serum biochemical analysis, plasma lactate concentration, and urinalysis remained within the reference range during phase 2 of the study. During phase 3, control of glycemia was achieved in 1 of 5 diabetic cats after 8 weeks of metformin treatment; 3 cats failed to respond to metformin, and treatment with insulin was initiated after 7-8 weeks of metformin treatment; 1 cat died unexpectedly 11 days after starting metformin treatment. The cause of death was not determined. The serum insulin concentration was within or greater than the reference range in the responder diabetic cat and was undetectable or at the low end of the reference range in the nonresponder diabetic cats. The results of this study suggest that metformin is beneficial only in those diabetic cats with detectable concentrations of insulin at the time metformin treatment is initiated.