Dirlotapide is a novel
microsomal triglyceride transfer protein inhibitor intended for the treatment and management of
obesity in dogs. The
biologic effects of
dirlotapide,
weight loss, decreased food intake, increased fecal fat, decreased serum
cholesterol, and body composition, were evaluated in a controlled, blinded study. Sixteen obese beagles were randomized to treatment with placebo (n = 4) or
dirlotapide (n = 12) following a 2-week acclimation period in which baseline data were collected. The
dirlotapide dose, adjusted to produce
weight loss for 3 months and then stabilize
body weight for 1 month (weight management), produced a significant difference (expressed as a percentage of baselines) in weekly
weight loss, food intake, fecal fat, serum
cholesterol concentration, and body composition (measured by dual energy X-ray absorptiometry) compared with placebo treatment (P < 0.05). The initial
dirlotapide dosage of 0.5 mg/kg (10 times the initial label dose) resulted in a high rate of
weight loss (3.3% weekly) and
anorexia,
emesis, and loose stools for some dogs. A 25%
dose reduction (mean dosage: 0.36 mg/kg) followed by biweekly 25% dose adjustments based on individual
weight loss, produced 1-2% weekly
weight loss and total
weight loss of 18.8% in 12 weeks at a final mean dosage of 0.41 mg/kg (range: 0.15-0.60); a dosage range of 0.10-0.34 mg/kg stabilized
body weight.
Body weight changes for placebo-treated dogs were -0.8% to +0.9% weekly; total
weight gain during the
weight loss phase was 10.6%. No apparent change in food intake, percentage of fecal fat, and serum
cholesterol was observed in the placebo group. Food intake and
body weight increased when
dirlotapide was discontinued.
Dirlotapide produced
weight loss by both reducing appetite (about 90% of the
weight loss activity) and by increasing fecal fat excretion (about 10% of the
weight loss activity).