Dirlotapide is a microsomal triglyceride transfer protein (MTP) inhibitor developed for use in dogs. MTP has an important role in the transfer of triglycerides, cholesterol ester, and phosphatidylcholine between membranes. This drug shows relative selectivity in vivo for inhibition of intestinal MTP activity. The effect of partial inhibition of intestinal MTP is that fatty acids, monoglycerides, and cholesterol from micelles of digested dietary fat stay in the enterocyte, blocking the production and release of lipoprotein particles into the circulation via lymphatics. This process results in decreased fat absorption from the intestinal lumen and increased excretion of fecal fat. The drug also decreases food intake in a dose-dependent manner. The gastrointestinal mucosa must be exposed to the drug for it to work. After oral administration, the drug is rapidly absorbed with peak plasma proteins being attained between 0.5 and 4 hours after dosing. As a dog loses weight, the dose must be increased to maintain consistent weight loss. In experimental dogs, the drug was well tolerated, although vomiting, intermittent loose stools, lethargy, and anorexia were noted. The signs were most commonly seen during the first month of therapy, at which time the dogs developed some tolerance. Vomiting and diarrhea over a 2-week period in a randomly selected group of client-owned dogs was 18.9% and 14.9%, respectively. These side effects were minimized by acclimating the dogs by using a low starting dose of 0.5 mg/kg and doubling this after 2 weeks. The drug dose is tapered as the ideal weight is reached.

Study by Pfizer LTD

Dirlotapide: A review of its properties and role in the management of obesity. Wren JA, Gossellin J, Sunderland SJ. J VET PHARMACOL THER 30:11-16, 2007.


• Fat absorption from the intestinal lumen decreases and excretion of fecal fat increases with dirlotapide.
• The drug decreases food intake in a dose-dependent manner.
• It is generally well tolerated, but vomiting, intermittent loose stools, lethargy, and anorexia were noted.
•These consensual recommendations reflect a combination of expert opinion, personal experience, and scientific studies.
• They should not be construed as exclusive protocols.
• The entire veterinary team, along with owners, should be involved in management of pain in pets.