ALLI

Pharmacotherapeutic group: antiobesity preparations, excl.‍​‍‍‍​‍‍‍‍‍‍‍‍​‍ diet products, peripherally acting antiobesity products, ATC code: A08AB01. Orlistat is a potent, specific and long-acting inhibitor of gastrointestinal lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the active serine site of the gastric and pancreatic lipases. The inactivated enzyme is thus unavailable to hydrolyse dietary fat, in the form of triglycerides, into absorbable free fatty acids and monoglycerides. From clinical studies, it has been estimated that orlistat 60 mg taken three times daily blocks the absorption of approximately 25% of dietary fat. The effect of orlistat results in an increase in faecal fat as early as 24 to 48 hours after dosing. Upon discontinuation of therapy, faecal fat content returns to pre-treatment levels, usually within 48 to 72 hours. Two double-blind, randomised, placebo-controlled studies in adults with a BMI ≥28 kg/m 2 support the efficacy of orlistat 60 mg taken three times daily in conjunction with a hypocaloric, lower-fat diet. The primary parameter, change in body weight from baseline (time of randomisation), was assessed for body weight over time (Table 1) and the percentage of subjects who lost ≥5% or ≥10% of body weight (Table 2). Although weight loss was assessed during 12 months of treatment in both studies, most weight loss occurred within the first 6 months. Table 1: Effect of 6 months treatment on body weight measured at baseline Treatment group N Relative mean change (%) Mean change (kg) Study 1 Placebo Orlistat 60 mg 204 216 -3.24 -5.55 -3.11 -5.20 a Study 2 Placebo Orlistat 60 mg 183 191 -1.17 -3.66 -1.05 -3.59 a Pooled data Placebo Orlistat 60 mg 387 407 -2.20 -4.60 -2.09 -4.40 a a p <0.001 versus placebo Table 2: Responder analysis at 6 months Lost ≥5% of baseline body weight (%) Lost ≥10% of baseline body weight (%) Placebo Orlistat 60 mg Placebo Orlistat 60 mg Study 1 30.9 54.6 a 10.3 21.3 b Study 2 21.3 37.7 a 2.2 10.5 b Pooled data 26.4 46.7 a 6.5 16.2 a Comparison versus placebo: a p <0.001; b p <0.01 The weight loss induced by orlistat 60 mg conferred other important health benefits after 6 months of treatment in addition to weight loss. The mean relative change in total cholesterol was -2.4% for orlistat 60 mg (baseline 5.20 mmol/l) and +2.8% for placebo (baseline 5.26 mmol/l). The mean relative change in LDL cholesterol was -3.5% for orlistat 60 mg (baseline 3.30 mmol/l) and +3.8% for placebo (baseline 3.41 mmol/l). For waist circumference, the mean change was -4.5 cm for orlistat 60 mg (baseline 103.7 cm) and -3.6 cm for placebo (baseline 103.5 cm). All comparisons against placebo were statistically significant.