The Efficacy and Safety of Slentrol® (Dirlotapide), a Novel Microsomal Triglyceride Transfer Protein Inhibitor, Administered Daily for up to 52 Weeks in Overweight Labradors
J. Gossellin; S. Peachey; J. Sherington; T.G. Rowan; S.J. Sunderland
Veterinary Medicine Research and Development, Pfizer Ltd.
Sandwich, Kent, UK
Dirlotapide causes body weight reduction in obese dogs primarily due to reductions in food intake.
To investigate the efficacy and safety of dirlotapide in overweight Labradors in two masked, parallel-design studies.
Study A: 42 dogs randomised to 0.0, 0.025, 0.05, 0.1, 0.2 or 0.4 mg dirlotapide/kg/day orally for 4 weeks. Study B: 72 dogs randomised 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, offered in excess of maintenance requirements. Dogs were weighed and dirlotapide dose (initially 0.1 mg/kg) was adjusted monthly. After 24 weeks, dosages were reduced to stabilise body weight. Body composition (body fat, lean tissue and bone mineral content) was monitored using dual-energy x-ray absorptiometry. Multiple blood samples were collected for haematology and biochemistry.
Study A: body weight and food intake decreased asymptotically with dose, mean weekly weight losses were 1.13-1.76% at 0.1-0.4 mg/kg. Study B: compared with placebo, dirlotapide resulted in significant mean weekly weight loss (0.86%) and decreased food intake for all diets during 24 weeks (P=0.0001), with mean weight loss ranging between 18.4% and 22.3% across diets after 24 weeks. Fat tissue decreased but lean tissue mass was maintained. Intermittent, mild and self-limiting, emesis and loose stools were observed for dirlotapide and placebo.
Dirlotapide administered daily to dogs for up to 52 weeks was clinically safe and resulted in sustained weight reduction regardless of dietary fat level.