Skin Care , Cosmatic , Weight Control, Obesity, Slimmer By Dr. JAKKAPOB ! (Long-term Studies of Pharmacotherapy for the Management of Obesity)

Long-term Studies of Pharmacotherapy for the Management of Obesity

Table of studies summarized in "Long-term Pharmacotherapy in the Management of Obesisty." S
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/m 2 ) at Baseline 1	Change in Weight (kg) or BMI (kg/m 2 ) at Endpoint 2	% 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%)	NR 2	-8.9 3 -10.5	NR	13 4 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	-11.7 4,5 -2.5	12.7 3.0	80 5, 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	65 5, 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 N 6 100 H 16 N + H	80 (93%) 96 (96%) 15 (94%)	76.8 85.6 72.5	-7.6 4 -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 weeks 7	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	32 8 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	+0.3 5 +1.3	NR	NR
Pedrinola et al, 1995 (53)	Non-randomized placebo controlled	55% F 10 Children 11-17 y, BMI range 24.5-44.0 kg/m 2	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/m2 6,11 -1.3 kg/m2 12	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 ? 8.6 6,13 -7.2 ? 8.6	9.9 7.3	35 6 17
O'Connor et al., 1995 (57)	Double-blind placebo controlled	78% F (Drug) 42% F (Placebo), 18-64 y, BMI 30-40 kg/m 2	6 months active drug after one month single- blind placebo run in 14	"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/m 2 11 35.6 ? 2.9 kg/m 2	-9.7 ? 5.7 4,6 -4.9 ? 4.4	10.4 4.9	50 6 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 ? 4.8 11 100.8 ? 3.9	-6.2 ? 1.1 4,6 -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 ?2.6 15 -8.3 ?1.7	11.8 7.5	53 6,16 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 ? 10.4 4,17 -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/m 2	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	24 18,19 20 19 24 20 20 22	21 (88%) 19, 20 18 (90%) 15 (79%) 18 (75%) 18 (90%) 17 (85%) 18 (82%)	91.4 19 90.9 89.7 87.2 90.9 95.8 92.0	-8.3 ? 2.6 5,19,20 -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/m 2	6 months	5020 -6700 kJ/d (1200- 1600 kcal/d)diet	fluoxetine 60 mg/d placebo	15 15	11 (73%) 13 (87%)	92.0 22 85.1	-3.9 6,23 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/m 2	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 ? 8.7 4 -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/m 2	12 months	"Continue usual lifestyle, medications"	fluoxetine 60 mg/d placebo	9 10	7 (78%) 9 (90%)	97.5 23 97.8	-4.3 6,23 +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/m 2	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 ? 11.6 23 89.2 ? 14.2 89.1 ?11.8	-1.6 24 -2.0 -3.5	NR 25	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%)	102.8 26 104.5	-8.5 ? 12.6 4 -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/m 2 33.4 ? 2.9 kg/m 2	-14.3 ? 6.9 4,6 -4.6 ? 5.9	15.6 4.9	NR

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