Long-term Studies of Pharmacotherapy for the Management of Obesity

Table of studies summarized in "Long-term Pharmacotherapy in the Management of Obesity."
National Task Force on the Prevention and Treatment of Obesity. JAMA. 1996; 276:1907-1915.

Author and
Reference
(Numbers refer to references in JAMA paper).
Type of Study Subject
Characteristics
Duration of
Treatment
Nondrug
Interventions
Study
Groups
Initial
Number
of
Subjects
Final Number of Subjects
(% Completing Study)
Weight (kg)
or BMI
(kg/m2) at
Baseline1
Change in Weight
(kg) or BMI
(kg/m2) at Endpoint2
%
Reduction
in Weight
at Endpoint
% losing
> 10% Initial
Body Weight
Silverstone and
Solomon, 1965
(42)
Randomized,
double-blind,
placebo-
controlled
100% F, 20-60 y,
mean 12.6 kg above
IBW
52 weeks
(30 days
medication or
placebo
alternating
with 30 days
without medication)
Low
carbohydrate
diet
diethylpropion 75mg/d

placebo

16


16

5 (31%)


6 (38%)

NR2


-8.93


-10.5

NR


134


19

McKay, 1973 (43) Randomized,
double-blind,
placebo-
controlled
70% F, mean age
32.5 (drug) and
34.7 (placebo)"diet
resistant", 15-20%
overweight
24 weeks "Strict diet" diethylpropion 75 mg/d

placebo

10


10

7 (70%)


4 (40%)

92.3


84.5

-11.74,5


-2.5

12.7


3.0

805, 6


0

Munro et al., 1968
(46)
Double blind,
placebo
controlled
100% F , 21-60 y,
>20% overweight
36 weeks 4200 kJ/d
(1000 kcal/d)
diet
phentermine 30 mg/d

Intermittent
phentermine 30
mg/d and placebo

placebo

36


36


36

17 (47%)


22 (61%)


25 (69%)

94.1


97.3


92.3

-12.2 ± 7.3 4,6


-13.0 ± 7.5


-4.8 ± 5.1

13.0


13.4


5.2

655, 6


64


20

Hudson, 1977 (48) Open-label
with
concurrent
diet-only
control
81% F, 15-75 y 12 months Low
carbohydrate
diet
d,l fenfluramine
80-120 mg/d

diet alone

86 N6
100 H

16 N + H

80 (93%)
96 (96%)

15 (94%)

76.8
85.6

72.5

-7.64
-8.7

-4.5

9.9
10.2

6.2

NR


Sensi et al., 1985
(49)
Randomized
open-label
with diet only
control
78% F, 18-56 y,
mean 52-66%
overweight
24 weeks7 5040 kJ/d
(1200 kcal/d)
diet
d,l fenfluramine
(F) 60 mg once/d
F 40 mg once/d

F 20 mg 3 times/d

diet alone

35

34

37

50

9 (26%)

8 (24%)

16 (43%)

13 (26%)

90.4 ± 15.9

86.5 ± 11.1

90.8 ± 12.8

83.4 ± 16.2

-10.6 ± 5.4

-12.7 ± 5.1

-11.9 ± 7.3

-9.5 ± 5.5

11.7

14.7

13.1

11.4

NR
Stunkard et al.,
1980 (50),
Craighead et al.,
1981 (51)
Open label
with drug
only,
behavioral
treatment-
only, 2
behavioral
treatment +
drug groups
and wait-list
controls
90%F, 23-69 y, 21-
156% overweight
6 months drug
treatment
Nutritional
counseling on
4200-5020
kJ/d (1000-
1200 kcal/d)
diet
d,l fenfluramine up
to 120 mg/d (F)-
group setting

Behavioral
treatment (BT)

BT + F

F alone (doctor's
office treatment)

wait-list control

328


39


31


8


10

25 (7 8%)


32 (82%)


23 (74%)


6 (75%)


10 (100%)

95.6 ± 17.5


91.6 ± 13.7


98.1 ± 20.0


82.2 ± 17.3


93.1 ± 19.0

-14.5 ± 5.5 4,6


-10.9 ± 5.7


-15.3 ± 5.8


-6.0 ± 4.2


+1.3 ± 4.1

15.2


11.9


15.6


7.3


+1.4

NR
Douglas et al.,
1983 (52)
Double blind
placebo
controlled
100% F mean age 47,
at least 15%
overweight, who
lost at least 6 kg.
on open-label d,l
fenfluramine for
26 weeks
52 weeks
after four
week double-
blind
crossover
NR d,l fenfluramine 60 mg/d - 300 mg/d

placebo

21


21

8 (38%)9


2 (10%)

NR


NR

+0.35


+1.3

NR NR
Pedrinola et al,
1995 (53)
Non-randomized
placebo
controlled
55% F10
Children 11-17 y,
BMI range 24.5-44.0
kg/m2
12 months 3340--4200
kJ/d (800-
1000 kcal/d)
diet,
instructed to
increase exercise.
d,l fenfluramine
30-60 mg 2 times/d

placebo

90


40

68 (76%)


17 (42%)

29.2 ±
4.5 kg/m2

29.9 ± 4.3
kg/m2

-5.1 kg/m26,11

-1.3 kg/m212

NR


NR

NR
Guy Grand et al.
1989 (37)
Multi-center,
randomized
double-blind,
placebo-
control led
81% F, 18-74y,
>120% IBW
12 months Low-calorie
or very low
calorie diet,
exercise,
behavioral
counseling
(varied by
site)
dexfenfluramine 15 mg 2 times/d

placebo

404


418

254 (63%)


229 (55%)

98.6 ± 18.1


98.0 ±
13.6

-9.8 ± 8.66,13


-7.2 ± 8.6

9.9


7.3

356


17

O'Connor et al.,
1995 (57)
Double-blind
placebo
controlled
78% F (Drug)
42% F (Placebo),
18-64 y,
BMI 30-40
kg/m2
6 months
active drug
after one
month single-
blind placebo
run in14
"dietary
education,
prescribed exercise,
behavior
modification"
dexfenfluramine 15
mg/d-15 mg 2
times/d

placebo

30

28

27 (90%)

24 (86%)

34.8 ± 3.1
kg/m2 11

35.6 ± 2.9
kg/m2

-9.7 ± 5.7 4,6

-4.9 ± 4.4

10.4

4.9

506

14

Noble, 1990 (58) Randomized,
double-blind
placebo
-controlled
78% F, >18 y, >110%
IBW, who had lost
>4.5 kg, but had
not lost additional
weight in the past
month
24 weeks 5020 -6270
kJ/d (1200-
1500
kcal/d)diet
and nutrition
counseling
dexfenfluramine 15 mg 2 times/d

placebo

30

30

19 (63%)

23 (77%)

90.0 ± 4.811

100.8 ± 3.9

-6.2 ± 1.14,6

-2.6 ±1.5

6.8

2.6

NR
Mathus-Vliegen,
1993 (59)
Randomized
double-blind,
placebo-
controlled
80% F, >18 y ,
>120% IBW
12 months Half of
calculated number of
calories, or
4200 kJ (1000
kcal) less
than reported
dexfenfluramine 15 mg 2 times/d

placebo

21

21

17 (81%)

18 (86%)

107.8 ±
16.9

110.9 ±
12.8

-12.8 ±2.615

-8.3 ±1.7

11.8

7.5

536,16

28

Finer et al., 1989(60), Finer, 1992 (61) Randomized
double blind
placebo
controlled
Patients treated
with medication
after an 8 week
very low calorie
diet (VLCD)
26 weeks
after 8 week
VLCD
run-in
Low calorie
diet to
provide 60-
75% of
calculated
energy needs
dexfenfluramine 15
mg 2 times/d

placebo

23

22

16 (70%)

16 (73%)

122.8 ±
21.6

120.8
± 23.0

-21.3 ± 10.44,17

-11.3 ± 7.6

17.3

9.4

NR
Bray et al., 1996
(62)
Randomized
double blind
placebo
controlled
86% F, 18-65 y, BMI
30-40 kg/m2
24 weeks
after 2 week placebo run-
in
individualize
d 5020-6270
kJ/d (1200-
1500 kcal/d)
diet and
prescribed
exercise
sibutramine
30 mg/d
20 mg/d
15 mg/d
10 mg/d
5 mg/d
1 mg/d

placebo

2418,19
20
19
24
20
20

22

21 (88%)19, 20
18 (90%)
15 (79%)
18 (75%)
18 (90%)
17 (85%)

18 (82%)

91.419
90.9
89.7
87.2
90.9
95.8

92.0

-8.3 ± 2.65,19,20
-7.3 ± 2.5
-6.9 ± 2.5
-6.1 ± 2.3
-2.9 ± 2.6
-3.0 ± 2.6

-0.8 ± 2.5

9.2
8.1
7.8
6.9
3.1
3.2

0.8

35 5,21
38
28
16
16
8

0

Connolly et al.,
1995 (64)
Randomized,
double-blind,
placebo-
controlled
9% F, (Drug)
61% F (Placebo)
Diet-controlled
noninsulin-
depdendent
diabetics >60 y,
BMI > 29 kg/m2
6 months 5020 -6700
kJ/d (1200-
1600 kcal/d)diet
fluoxetine 60 mg/d

placebo

15

15

11 (73%)

13 (87%)

92.022

85.1

-3.96,23

0

4 .2

0

NR
Goldstein et al.,
1994 (38)
Multi-center,
randomized
double-blind,
placebo-
controlled
81% F (Drug), 79% F
(Placebo) , mean
age 43, BMI >25
kg/m2
52 weeks Individualize
d diet,
nutrition and
behavioral
counseling (varied by
site)
fluoxetine 60 mg/d

placebo

230

228

99 (43%)

108 47%)

100.3 ±
19.4

99.2 ± 20.1

-1.7 ± 8.74

-2.1 ± 6.8

1.7

2.1

NR
O'Kane et al., 1994
(65)
Randomized,
double-blind,
placebo-
controlled
68% F,
Noninsulin-
dependent diabetics
on oral
medications, 23-72
y, BMI > 30 kg/m2
12 months "Continue
usual
lifestyle,
medications"
fluoxetine 60 mg/d

placebo

9

10

7 (78%)

9 (90%)

97.523

97.8

-4.36,23

+1.5

4.4

+1.5

NR
Goldstein et al., 1993 (39) Multi-center,
randomized
double-blind,
placebo-
controlled
79% F, Outpatients
who had lost >3.6
kg after single-
blind fluoxetine,
age >18, BMI 30-39
kg/m2
40 week
double-blind
maintenance
phase
following 8
week open-
label trial
Individualize
d diet,
nutrition and
behavioral
counseling (varied by
site)
fluoxetine 60 mg/d

fluoxetine 20 mg/d

placebo

106

104

107

60 (57%)

70 (67%)

72 (67%)

84.9 ±
11.623

89.2 ± 14.2

89.1 ±11.8

-1.624

-2.0

-3.5

NR25 NR
Wadden et al., 1995
(66)
Randomized
double blind
placebo
controlled
100% F, mean age
42. who had lost a
mean of 24.1 kg
(drug) or 21.8 kg
(placebo) on a very
low calorie diet
54 week
maintenance
phase following 26
week VLCD
Behavioral
relapse
prevention
6270-7520
kJ/d (1500-
1800 kcal/d)
diet
sertraline 200 mg/d

placebo

26

27

13 (50%)

17 (63%)

102.826

104.5

-8.5 ± 12.64

-11.6 ± 6.9

8.2

11.7

NR
Weintraub et al.,
1992 (11-19)
Randomized,
double-blind
placebo-
controlled (6
week no-drug
run in)
74% F, 18-60 y,
130-180% IBW
28 weeks
followed by
open-label
trial and
second double
-blind study
(see text)
Diet,
exercise,
behavior
modification
d,l fenfluramine 60
mg /d, plus
phentermine 15 mg
/d

placebo

62

59

58 (94%)27

54 (92%)

33.5 ±
2.3 kg/m2

33.4 ± 2.9
kg/m2

-14.3 ± 6.94,6

-4.6 ± 5.9

15.6

4.9

NR


1IBW=ideal body weight, BMI=body mass index
2mean ±SD when reported
3NR=not reported
4Completers only
5Last observation carried forward
6p<0.05, drug vs. placebo or nondrug control
7N=normotensive, H=hypertensive
8Trial designed for 36 weeks, but most data only available for patients completing 24 weeks.
9Data reported for women only
10Patients were discontinued from study if they regained 50% of initial weight loss or 4 kg, whichever was greater. 19/21 placebo-assigned patients and 7/21 fenfluramine assigned patients were withdrawn from the study for this reason.
11Initial data presented for completers only
12Change in BMI reported (in kg/m2) for 68 subjects available at end of study
13Change in BMI reported (in kg/m2) for completers only
14 Data available on 295 patients in medication group and 268 in placebo group.
15Results from an additional non-drug follow-up phase are not reported in this table.
16Data on weight loss available on 5/7 non-completers at 12 months
17Estimated from Mathus-Vliegen's Figure 1, ref 59. Weight loss is from baseline before open-label qualification phase.
18Includes weight loss from VLCD run-in
19Data included for women only. Results for men were similar, and are reported in ref 66.
20Unpublished data provided by Donna Ryan, Pennington Biomedical Research Center, Baton Rouge, La. July 18, 1996.
21p<0.05, vs placebo for all treatment groups except 1 and 5 mg.
22p<0.05 vs. placebo for all treatment groups except 1 mg.
23Results expressed as median with interquartile ranges
24 Weights are reported at randomization, after open-label qualification phase.
25Estimated from Goldstein and coworkers Figure 2, ref. 39.
26 % weight loss from baseline cannot be calculated, because pre-run in weights for the three groups are not provided
27Baseline (pre-VLCD) weights for subjects randomized to maintenance trial
28N at end of first open-label phase (week 34). At week 190, 51 patients of the original 121 (42%) remained in the study.