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	-11.7^4,5 -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 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/m2^6,11 -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 ± 8.6^6,13 -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/m^{2 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 ± 1.1^4,6 -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 ±2.6¹⁵ -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/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	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%)	91.4¹⁹ 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/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	-3.9^6,23 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/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	-4.3^6,23 +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/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 ± 6.9^4,6 -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
²⁴Weights 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.

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