Denise A. Elliott

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.

Effect of age at gonadectomy on the probability of dogs becoming overweight

OBJECTIVE To determine whether gonadectomy or age at gonadectomy was associated with the risk that dogs would subsequently become overweight. DESIGN Retrospective cohort study. ANIMALS 1,930 dogs gonadectomized between 1998 and 2001 at ≤ 6 months of age (n = 782), > 6 months to ≤ 1 year of age (861), or > 1 to ≤ 5 years of age (287) and 1,669 sexually intact dogs. PROCEDURES Dogs were followed-up through medical records for ≥ 10 years or until a diagnosis of overweight (defined as overweight, obese, or having a body condition score ≥ 4/5) was recorded. Information extracted included age at study entry, sex, breed, breed-size category, hospital visit frequency, and diagnosis (yes or no) of overweight or diseases that might affect body condition. Relative risk of a diagnosis of overweight was assessed among age groups of gonadectomized dogs and between gonadectomized and sexually intact dogs. RESULTS No difference was detected among dogs grouped according to age at gonadectomy with respect to the risk of being overweight. This risk was significantly greater in gonadectomized dogs than in sexually intact dogs, but only during the first 2 years after gonadectomy. Sexually intact male dogs were approximately 40% less likely to have this diagnosis (hazard ratio, 0.61; 95% confidence interval, 0.52 to 0.72) than were sexually intact female dogs; no difference in risk between the sexes was evident for gonadectomized dogs. CONCLUSIONS AND CLINICAL RELEVANCE Gonadectomized dogs had a greater risk of being overweight than did sexually intact dogs, but this risk was not influenced by age at gonadectomy. Opportunities exist for veterinarians to provide counseling during the first years after gonadectomy to help dogs maintain a healthy weight.