ABSTRACT
Table 1 Some Criteria for Assessing Success in Treatment for Obesity
Author (Ref.) Stunkard
and McLarenHume (I)
Atkinson (5)
Criteria
Percent losing >20 Ib (9 kg) Percent losing >40 Ib (18.1 kg)
Success: (initial wt in Ib lost sl50 Ib ;;::10 Ib, 151-1751b ;;::15Ib, 176-200 Ib/ 201b, 201-225 Ib/25 Ib, 225-250 Ib/30 Ib, ;;::251 Ib/ 35 Ib
Failure: s5 Ib wt loss in ;;::4 months Reduction index = wt (lost)
> 0.5 Ib/wk more than placebo Percent losing > I Ib/wk or
> 3 Ib/wk ;;:: 10% loss of excess weight for
>6 mo Loss of ;;::2 BMI units for > 6 mo Reduction in comorbidities
for >6 mo ;;::5% wt loss if BMI > 27 kg/m2 ;;::20% loss of excess body weight >5% reduction in visceral fat Significant improvements in
comorbidities
Table 2 Regulatory Criteria for Establishing Efficacy of Antiobesity Drugs
FDA Criteria (7)
CPMP Criteria (8) Early trials
Type of trial Duration Inclusion Ancillary
10 Endpoint No. patients Tolerability Mechanism of action Pharmacokinetics Toxicology studies Drug interactions
Long-term Type of trial Duration
Inclusion
Ancillary advice Run-in Measures 10 Endpoint
20 Endpoints
Subjects
Randomized, double-blind, placebo-controlled Dose-ranging; identify lowest effective dose 3-6 months BMI>30 kg/m2 Similar advice in diet, exercise, and behavior
Wt loss significantly greater than placebo About 200, including both sexes and minorities Yes Yes Yes Yes Yes
Randomized, double-blind, placebo-controlled Efficacy and safety Year I: double-blind Year 2: open-label or double-blind BMI > 30 kg/m2 of otherwise healthy or
BMI >27 kg/m2 with comorbidities Moderately restricted diet and exercise Identify placebo responders; stratify; 6 wks Body weight, body fat, and fat distribution Wt loss significantly greater than placebo
and S% > placebo at 12 mo Significantly greater no. 8 achieving >S% wt loss
Maintenance of weight loss Significant change in body fat and fat
distribution (may stratify-fat distribution risk factors, severity, duration, age)
Improved cardiovascular risk factor Improved metabolic profile Improved quality of life
Male and female; minorities About ISOO to complete 12 mo with
200-SOO completing 2 years
Not specified Not specified Not specified Effective nonpharmacological
therapy Wt loss that is fat loss Not specified Yes Yes Yes Yes Yes 12 mo-open-label or random 24 hr Efficacy and safety At least I year
BMI > 30 kg/m2 of otherwise healthy or BMI >27 kg/m2 with comorbidities
Weight reducing diet; beh. mod; exercise Yes Body weight, body fat, and fat distribution Wt loss 10% below baseline and
significantly> placebo at 12 mo Significantly greater no. 8 achieving
>10% wt loss Maintenance of weight loss Improved biochemical parameters Reduction in cardiovascular risk Decreased blood pressure Decreased apneic episodes Loss of body fat and/or visceral fat Improved joint mobility Improved male and female infertility Improved quality of life Male and female
Time (weeks)
PLACEBO ALONE PLACEBO + BEHAVIOR
MODIFICATION
Treatment outcomes and interpretation
Figure 3 Evaluation of treatment outcomes in relation to the natural history of obesity and the degrees of weight loss that can be achieved. (From Ref. 19.)
noted. After a brief discussion of the mechanisms of action of the drugs under review, we will return to a review of clinical trials using these medications.
