A comparative study of five centrally acting drugs on the pharmacological treatment of obesity.

CONTEXT: No long-term studies have compared centrally acting drugs for treating obesity. OBJECTIVE: To compare the efficacy and safety of diethylpropion (DEP), fenproporex (FEN), mazindol (MZD), fluoxetine (FXT) and sibutramine (SIB) in promoting weight loss. DESIGN AND SETTING: A prospective, randomized, placebo (PCB)-controlled study conducted at a single academic institution. PATIENTS: A total of 174 obese premenopausal women. INTERVENTION: Participants randomly received DEP 75 mg (n=28), FEN 25 mg (n=29), MZD 2 mg (n=29), SIB 15 mg (n=30), FXT 20 mg (n=29) or PCB (n=29) daily over 52 weeks. Diet and physical activity were encouraged. MAIN OUTCOME MEASURES: The primary endpoints were changes in body weight and the proportion of women who achieved at least 5% weight loss by week 52 in the intent-to-treat population. Other measurements included anthropometry, safety, metabolic and cardiovascular parameters. RESULTS: Weight loss was greater than PCB (-3.1±4.3 kg) with DEP (-10.0±6.4 kg; P<0.001), SIB (-9.5±5.9 kg; P<0.001), FEN (-7.8±6.9 kg; P<0.01) and MZD (-7.4±4.9 kg; P<0.01) but not with FXT (-2.5±4.1 kg). Ten (33.3%) women lost⩾5% of their initial weight with PCB, compared with 20 (71.4%; P<0.001) with DEP, 20 (69%; P<0.02) with FEN, 21 (72.4%; P<0.01) with MZD, 22 (73.3%; P<0.001) with SIB and 10 (35.5%) with FXT. Each medically treated group experienced more adverse events compared with PCB (P<0.001). Compared with PCB, constipation was more prevalent with DEP, SIB and MZD (P<0.01); anxiety was more prevalent with DEP (P=0.01); and irritability occurred more frequently with DEP and FEN (P=0.02). Significant improvements in the depression and anxiety scores, binge-eating episodes and quality of life correlated with weight loss. CONCLUSION: The centrally acting drugs DEP, FEN, MZD and SIB were more effective than PCB in promoting weight loss in obese premenopausal women, with a satisfactory benefit-risk profile.

Butyrylcholinesterase and obesity in individuals with the CHE2 C5+ and CHE2 C5- phenotypes.

OBJECTIVE: To investigate the association between butyrylcholinesterase (BChE) activities (total and band specific) and body mass index (BMI) in obese and nonobese individuals, considering other variables (anthropometric, biochemical and hormonal) and the leanness process. SUBJECTS: Obese (BMI> or =30 kg/m(2); N=181) and nonobese individuals (N=265), classified according to the CHE2 locus phenotypes, with the obese patients being followed-up when submitted to a weight-loss program. MEASUREMENTS: Anthropometric (weight, height, BMI, waist, waist/hip ratio-WHR, triceps and subscapular skinfolds, percentage of body fat and arterial pressures), hormonal (insulin, estradiol-E(2), triiodothyronine-T(3) and thyroxine-T(4)) and biochemical (glucose, total cholesterol, HDL-C, triglycerides, uric acid, urea, creatinine, sodium, potassium and BChE activities) variables. RESULTS: Although obese CHE2 C5- individuals presented higher mean BChE activities than their CHE2 C5- controls and diminished mean activities with leanness, similar comparisons did not show any difference in the CHE2 C5+ group. Furthermore, the mean serum potassium values of obese individuals were significantly higher in the CHE2 C5+ than in the CHE2 C5- phenotype. The BChE activities were less related to BMI in obese CHE2 C5- individuals than in their controls. In the CHE2 C5- obese group, significant regression coefficients were found between BChE activity variables and BMI (+), ethnic origin (higher in Euro-Brazilians), sex (higher in males), diastolic pressure (-), triceps skinfold (+), total cholesterol (+), T(3) (+) and E(2) (-). The main findings in the CHE2 C5+ obese group: mean insulin levels decreased with leanness and a significant correlation was detected between the C(5) complex activity and creatinine (+), insulin (-) and WHR (-); a significantly higher frequency of weight loss occurred compared to the CHE2 C5- group. CONCLUSION: In the present study, different relations between obesity and some of the studied variables were found when CHE2 C5+ and CHE2 C5- individuals were compared.

Latin-American trial of orlistat for weight loss and improvement in glycaemic profile in obese diabetic patients.

AIM: To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat. DESIGN: Double-blind, parallel, randomized, placebo-controlled, multicentre study. SUBJECTS: Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin-American centres, in five countries. EFFICACY AND TOLERABILITY MEASUREMENTS: After screened, eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline. RESULTS: After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 +/- 0.23 vs. 2.58 +/- 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost > or = 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat-treated patients had a mean decrease in glucose levels of 1.00 +/- 0.34 mmol/l [3.7%] vs. 0.01 +/- 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 +/- 0.15 vs. a decrease of 0.22 +/- 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL-cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low. CONCLUSION: Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile.