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
|
5 (31%)
|
NR2 |
-8.93
|
NR |
134
|
| 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
|
7 (70%)
|
92.3
|
-11.74,5
|
12.7
|
805, 6
|
| 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 placebo |
36
|
17 (47%)
|
94.1
|
-12.2 ± 7.3 4,6
|
13.0
|
655,
6
|
| 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 BT + F F alone (doctor's wait-list control |
328
|
25 (7 8%)
|
95.6 ± 17.5
|
-14.5 ± 5.5 4,6
|
15.2
|
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
|
8 (38%)9
|
NR
|
+0.35
|
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
|
68 (76%)
|
29.2 ± 4.5 kg/m2 29.9 ±
4.3 |
-5.1 kg/m26,11 -1.3 kg/m212 |
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
|
254 (63%)
|
98.6 ± 18.1
|
-9.8 ± 8.66,13
|
9.9
|
356
|
| 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 |
-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 ±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 |
-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 |
-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.