Obese cats with diabetes can be frustrating to manage. Obesity is often associated with insulin resistance characterized by hepatic overproduction of glucose and a decrease in glucose uptake by peripheral tissues. Thiazolidinediones, a new class of antidiabetic drug that works in humans and rodents by increasing insulin sensitivity, are already being used extensively in humans for treating type 2 diabetes. Because cats have the same insulin secretion pattern as humans, a compound of the thiazolidinedione class, darglitazone, may be useful in treating obese cats. Darglitazone is believed to increase the sensitivity to insulin by decreasing hepatic output of glucose, increasing peripheral glucose uptake, and altering lipid metabolism. In this study, neutered female cats were divided into 2 groups: 1 group (9 obese cats) was examined before and after daily administration of darglitazone, and another group (9 obese and 4 lean cats) was given placebo. Intravenous glucose tolerance tests measured glucose, insulin, and nonesterfied fatty acid (NEFA) concentrations before and 42 days after treatment. Cholesterol, triglyceride, leptin, and glycosylated hemoglobin concentrations were also measured.

Treated cats had significantly lower cholesterol, triglyceride, and leptin concentrations than placebo-treated obese cats. A significant decrease in NEFAs, glucose, and insulin was seen in treated cats, as was a significant decrease in the area under the curve for glucose and insulin during an IV glucose tolerance test in darglitazone-treated cats.

Darglitazone was well tolerated, and response to the drug was similar to that of humans and rodents. Unlike in humans, however, no increase in weight or food intake was observed during treatment, and weight was maintained during the study even though insulin sensitivity and glucose and lipid metabolism improved. The mechanism of action of thiazolidinediones is still controversial, and long-term effects need to be studied.

COMMENTARY: Obesity is a precursor to type 2 diabetes in cats, and investigators are focusing on drugs that may prevent progression of glucose intolerance to overt diabetes mellitus. This study of obese cats showed that compared with placebo-treated controls, obese cats treated with darglitazone, a promising new drug, had significantly lower cholesterol, triglyceride, and leptin concentrations.

Effect of darglitazone on glucose clearance and lipid metabolism in obese cats. Hoenig M, Ferguson DC. AM J VET RES 64:1409-1413, 2003.