New FDA-Approved Canine Obesity Drug Dirlotapide (Slentrol,, a microsomal triglyceride transfer protein (MTP) inhibitor, was recently approved by the FDA to treat obesity in dogs. MTPs act both as inhibitors of fat absorption across the intestinal luminal membrane and as appetite suppressors. They are endoplasmic reticulum proteins expressed primarily in the liver and intestinal tissue and play a pivotal role in assembly of lipids to apoprotein B, which is required for export of lipoproteins across cell membranes and transport of lipids in the circulation. Although the mechanisms for weight loss are not completely understood, it is thought that MTPs inhibit dietary lipid absorption and stimulate gut hormones that signal satiety. Dirlotapide appears to selectively decrease lipid absorption and chylomicron transport from the intestine, while avoiding hepatic lipid accumulation. Studies have shown that 90% of the resulting weight loss was from enhanced satiety resulting in decreased food intake rather than caloric loss due to fat malabsorption. It should be noted that dirlotapide is not a lipase inhibitor. Lipase inhibitors may promote significant lipid malabsorption, increasing stool frequency and causing loose, oily stools. Dirlotapide is intended to be used as part of an overall nutritional plan for weight loss on an intermittent or limited basis. Vomiting, soft stool, and diarrhea have been reported, but signs resolved on their own or upon withdrawal of the drug.

COMMENTARY: Although no magic pill, this pharmacologic intervention along with a diet and exercise may make a positive difference for obese dogs in the struggle to lose weight. Pet owners still need to be mindful of what they are feeding their pets and how much they are feeding them.

New treatment for canine obesity: Appetite control using MTP inhibitors. Kirk CA, Bartges JW. ACVIM PROC, 2007.