title: Evaluation of dirlotapide for sustained weight loss in overweight Labrador retrievers.
abstract: The effects of dirlotapide on body weight (BW) reduction were investigated in overweight Labradors in two parallel-design studies. Study A involved 42 dogs randomized to 0.0, 0.025, 0.05, 0.1, 0.2 or 0.4 mg dirlotapide/kg/day orally for 4 weeks. Study B involved 72 dogs randomized to nine treatments: placebo (24 weeks); dirlotapide (24 weeks) followed by placebo (28 weeks); or dirlotapide (52 weeks); on diets containing 5%, 10% or 15% fat. Dirlotapide dose (initially 0.1 mg/kg) was adjusted monthly during 24-week weight-loss and subsequent 28-week weight-stabilization phases. Food was offered above maintenance energy requirements (MERx 1.1-1.2) based on initial BW. Body composition (body fat, lean tissue and bone mineral content) was monitored using dual-energy X-ray absorptiometry. After treatment, dogs that had received dirlotapide for 52 weeks were fed 90% of quantity consumed at week 52. In study A, BW and food intake decreased asymptotically with dose: mean weekly weight loss exceeded 1% at 0.1-0.4 mg/kg. In study B, dirlotapide resulted in significant mean weekly weight loss (>0.8%) and decreased food intake over 24 weeks compared with placebo (P = 0.0001) for all diets. Food restriction minimized post-treatment weight rebound. Dirlotapide administered daily to dogs for up to 52 weeks was clinically safe and resulted in sustained weight reduction.
authors.affiliation: Pfizer Ltd, Veterinary Medicine Research and Development, Sandwich, Kent, UK. jacques.gossellin@pfizer.com
authors.forename: J
authors.initials: J
authors.lastname: Gossellin
authors.forename: S
authors.initials: S
authors.lastname: Peachey
authors.forename: J
authors.initials: J
authors.lastname: Sherington
authors.forename: T G
authors.initials: TG
authors.lastname: Rowan
authors.forename: S J
authors.initials: SJ
authors.lastname: Sunderland
mesh_terms: D015502:Absorptiometry, Photon / Q000662:veterinary; D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002219:Carbamates / Q000008:administration & dosage / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D004435:Eating; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010375:Pedigree; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D019440:Anti-Obesity Agents; D002219:Carbamates; D007211:Indoles; C521290:dirlotapide