Table 3. Randomized Controlled Trials of Pharmacotherapy Interventions

Study, Year	Drug Dose (mg)	Co-Interventions	Sample Size (N), Race, Sex, Age^a, Baseline BMI^b	Length, Goal	Groups	Weight Change	Between-Group Differences^c	P Value	Patients Lost to Followup and Adverse Events	Trial Quality
Sibutramine
Wirth and Krause, 2001⁸⁸	15 mg daily either continuous or intermitten	All participants: no formal diet, exercise, or behavioral program Written dietary information	N: 1102 White: 99.8% Female: 77% Sibutramine: Cont: 43 yrs Int: 43 yrs Placebo: 44 yrs Sibutramine: Cont: 34.7 kg/m² Int: 34.9 kg/m² Placebo: 35.0 kg/m²	44 wks, L	Sibutramine cont	-3.8 kg	-3.6 kg	< 0.001	Sibutramine (continuous): Dropout: 79/405 Due to adverse event: 25/405 Adverse event rate: 303/405 Sibutramine (intermittent): Dropout: 80/395 Due to adverse event: 13/395 Adverse event rate: 283/395 Placebo: Dropout: 55/201 Due to adverse event: 9/201 Adverse event rate: 151/201	Good
					Sibutramine int	-3.3 kg	-3.1 kg
					Placebo	-0.2 kg

						5% loss:
					Sibutramine con	65%	30%	< 0.001
					Sibutramine int	63%	28%
					Placebo	35%

						10% loss:
					Sibutramine con	32%	19%	< 0.001
					Sibutramine int	33%	20%
					Placebo	13%
Dujovne et al, 2001⁸⁵	20 mg daily	D All participants: Step I American Heart Association Diet (1500 kcal/d for females, 1800 kcal/day for males)	N: 322 White: 82% Black: 12% Indian or Pakistani: 1% Mexican American: 2% Other: 3% Drug: 56% female Placebo: 51% female Drug: 45 yrs Placebo: 46 yrs Sibutramine: 35.1 kg/m² Placebo: 35.5 kg/m²	24 wks, L	Sibutramine	-4.9 kg	-4.3 kg	< 0.05	Sibutramine: Dropout: 29.6% Due to adverse event: 9.9% Due to hypertension: 0.6% Placebo: Dropout: 33.8% Due to adverse event: 6.9% Due to hypertension: 1.9%	Fair
					Placebo	-0.6 kg

						5% loss:
					Sibutramine	42%	34%	< 0.05
					Placebo	8%

						10% loss:
					Sibutramine	12%	9%	< 0.05
					Placebo	3%

Fujioka et al, 2000⁸⁶	Titrated up to 20 mg daily	D All participants: 250-500 kcal/d caloric deficit diet with individual dietary counseling	N: 175 White: 73% Black: 17% Other: 10% Female: 47% Sibutramine: 53.5 yrs Placebo: 55.0 yrs Sibutramine: 34.1 kg/m² Placebo: 33.8 kg/m²	24 wks, L	Sibutramine	-3.7 kg	-3.3 kg	< 0.5	Sibutramine: Dropout: 29/89 Due to adverse event: 9/89 Placebo: Dropout: 25/86 Due to adverse event: 10/86	Fair
					Placebo	-0.4 kg

						5% loss:
					Sibutramine	27%	26%	< 0.001
					Placebo	1%

						10% loss:
					Sibutramine	6%	5%	0.12
					Placebo	1%

Gokcel et al, 2001³²	10 mg bid	D All participants: 25 kcal/kg ideal body weight diet, with counseling at baseline	N: 60 Race: NR Female: 100% Sibutramine: 47 yrs Placebo: 49 yrs Sibutramine: 39.3 kg/m² Placebo: 37.4 kg/m²	24 wks, L	Sibutramine	-3.9 kg	-4.3 kg	< 0.0001	Sibutramine: Dropout: 1/30 Due to adverse event: 1/30 Placebo: Dropout: 5/30 Due to adverse event: NR	Fair
Gokcel et al, 2001³²	10 mg bid			24 wks, L	Placebo	0.36 kg	-4.3 kg	< 0.0001		Fair
Smith and Goulder, 2001⁸⁷	10 mg or 15 mg daily	D All participants: dietary advice	N: 485 White: 99% Other: 1% Female: 80% Sibutramine: 10 mg: 41 yrs 15 mg: 43 yrs Placebo: 42 yrs Sibutramine: 10 mg group: 32.9 kg/m² 15 mg group: 32.7 kg/m² Placebo: 32.4 kg/m²	52 wks, L	Sibutramine: 10 mg	-4.4 kg	-2.8 kg	< 0.01	Sibutramine 10 mg: Dropout: 67/161 Due to adverse event: 2/161 Adverse event rate: 20/161 Sibutramine 15 mg: Dropout: 79/161 Due to adverse event: 2/161 Adverse event rate: 18/161 Placebo: Dropout: 83/163 Due to adverse event 4/163 Adverse event rate: 24/163	Fair
					Sibutramine: 15 mg	-6.4 kg	-4.8 kg
					Placebo	-1.6 kg

						5% Loss:
					Sibutramine: 10 mg	39%	19%	< 0.01
					Sibutramine: 15 mg	57%	37%
					Placebo	20%

						10% Loss
					Sibutramine: 10 mg	19%	12%	< 0.01
					Sibutramine: 15 mg	34%	27%
					Placebo	7%
McNulty et al, 2003³³	15-20 mg daily	D Standard dietary advice by a dietitian or nurse	N: 195 Race: NR Female: 56% 15 mg group: 49 yrs 20 mg group: 48 yrs Placebo: 51 yrs Sibutramine: 15 mg group: 36.3 kg/m² 20 mg group: 37.5 kg/m² Placebo: 36.2 kg/m²	12 mos, L	Sibutramine: 15 mg	-5.5 kg	-5.3 kg	< 0.001	Sibutramine 15 mg: Dropout: 19/68 Due to adverse event: NR Sibutramine 20 mg: Dropout: 13/62 Due to adverse event: NR Placebo: Dropout: 18/64 Due to adverse event: NR	Fair
					Sibutramine: 20 mg	-8.0 kg	-7.8 kg	< 0.001
					Placebo	-0.2 kg

						5% Loss:
					Sibutramine: 15 mg	46%	34%	Sibutramine "significantly more"
					Sibutramine: 20 mg	65%	53%
					Placebo	12%

						10% Loss:
					Sibutramine: 15 mg	14%	14%	NR
					Sibutramine: 20 mg	27%	27%
					Placebo	0%
James et al, 2000⁸⁴	10-20 daily	D,E,B All participants: high intensity individualized 600 kcal deficit diet	N: 467 "Almost all" white Afro-Caribbean: 2% Asian: 1.5% Female: 84% Sibutramine: 41 yrs Placebo: 40 yrs Sibutramine: 36.5 kg/m² Placebo: 36.6 kg/m²	80 wks, M (following 6 mos L phase)	Sibutramine	-8.9 kg	-4 kg	< 0.001	Sibutramine: Dropout: 148/352 Due to adverse event: 48/352 Placebo: Dropout: 58/115 Due to adverse event: 6/115	Fair
					Placebo	-4.9 kg

						Maintaining >80% of original loss:
					Sibutramine	41%
					Placebo	14%	27%	< 0.001
Orlistat
Muls et al, 2001⁹¹	120 mg	D All participants: moderate-intensity dietary advice from a dietitian (-600 kcal/day)	N: 294 Race: NR Orlistat: 82% Female Placebo: 78% Female Orlistat: 50 yrs Placebo: 48 yrs 33 kg/m²s	24 wks, L	Orlistat	-4.66 kg	-2.78 kg	< 0.001	Orlistat Dropout: 19/147 (13%) Adverse event rate: 80%^d GI Adverse event: 64% Placebo: Dropout: 16/147 (11%) Adverse event rate: 67% GI adverse event rate: 38%	Good
					Placebo	-1.88 kg

						Mean Change:
					Orlistat	-5.3%	-3%	< 0.001
					Placebo	-2.3%

						5% loss:
					Orlistat	64%	25%	NR
					Placebo	39%

						10% loss:
					Orlistat	23%	10%	NR
					Placebo	13%
Van Gaal et al, 1998⁸⁹	30, 60, 120, or 240 mg tid	D All participants: high-intensity dietary advice from a dietitian	N: 613 Race: NR Female: 77% Range: 40-44 yrs (varied by group) 34-35 kg/m² (varied by group)	52 wks, L	Orlistat: 30 mg	-8.5%	-2%	< 0.001	Orlistat 30 mg: Dropout: 29/122 Due to adverse event: 7/122 Adverse event rate: 79% Orlistat 60 mg: Dropout: 29/124 Due to adverse event: 6/124 Adverse event rate: 83% Orlistat 120 mg: Dropout: 23/122 Due to adverse event: 2/122 Adverse event rate: 84% Orlistat 240 mg: Dropout: 20/120 Due to adverse event: 3/120 Adverse event rate: 87% Placebo: Dropout: 27/125 Due to adverse event 3/125 Adverse event rate: 69%	Fair
					Orlistat: 60 mg	-8.8%	-2.3%
					Orlistat: 120 mg	-9.8%	-3.3%
					Orlistat: 240 mg	-9.3%	-2.8%
					Placebo	-6.5%

						10% Loss:
					Orlistat: 30 mg	28%	9%	NR
					Orlistat: 60 mg	28%	9%
					Orlistat: 120 mg	37%	18%
					Orlistat: 240 mg	38%	19%
					Placebo	19%
Micic et al, 1999⁹⁴	120 mg tid	D All participants: mildly hypocaloric diet with dietary advice	N: 119 Race: NR Orlistat: 70% female Placebo: 78% female Orlistat: 46 yrs Placebo: 45 yrs (median ages) Orlistat: 34.8 kg/m² Placebo: 35.2 kg/m²	24 wks, L	Orlistat	-10.8 kg	-3.5 kg	0.001	Orlistat: Dropout: 10/60 Due to adverse event: 1/60 Adverse event rate: 18/60 Placebo: Dropout: 10/59 Due to adverse event: NR Adverse event rate: 7/59	Fair
Micic et al, 1999⁹⁴	120 mg tid			24 wks, L	Placebo	-7.3 kg				Fair
Rissanen et al, 2001⁹⁵	120 mg tid	D All participants: 600 kcal deficit diet	N: 51 Race: NR Female: 100% Age: 44 yrs 36.2 kg/m²	12 mos, L	Orlistat	-13 kg	-5.8 kg	NS	Dropout: 4/55	Fair
Rissanen et al, 2001⁹⁵	120 mg tid	D All participants: 600 kcal deficit diet	N: 51 Race: NR Female: 100% Age: 44 yrs 36.2 kg/m²	12 mos, L	Placebo	-7.2 kg			Dropout: 4/55	Fair
Broom et al, 2002⁹⁶	120 mg tid	D All participants: mildly hypocaloric diet (minimum of 1200 kcal/day), with food and beverage diaries	N: 531 Race: NR Female: 78% Orlistat: 46.7 yrs Placebo: 45.3 yrs Orlistat: 37.1 kg/m² Placebo: 37.0 kg/m²	54 wks, L	Orlistat	-5.8 kg	-3.5 kg	< 0.001	Orlistat: Dropout: 79/265 Due to adverse event: 20/265 Due to GI symptoms: 13/265 Serious adverse events: 13/265 Placebo: Dropout: 105/266 Due to adverse event: 11/266 Due to GI symptoms: 6/266 Serious adverse events: 17/266	Fair
					Placebo	-2.3 kg

						>5% Loss:
					Orlistat	55.6%	31.3%	< 0.001
					Placebo	24.3%

						>10% Loss:
					Orlistat	19.7%	8.7%	NS
					Placebo	11.0%
Miles et al, 2002⁹⁰	120 mg tid	D, E All participants: recommended to increase physical activity and diet (-600 kcal/day) with dietary counseling throughout the study	N: 516 Orlistat: White: 84% Black: 10% Other: 6% Placebo: White: 79% Black: 14% Other: 7% Female: 48% Orlistat: 52.5 yrs Placebo: 53.7 yrs Orlistat: 35.2 kg/m² Placebo: 35.6 kg/m²	52 wks, L	Orlistat	-4.7 kg	-2.9 kg	< 0.001	Orlistat: Dropout: 35% Due to adverse event: 10% Due to GI symptoms: NR GI event frequency: 83% Placebo: Dropout: 44% Due to adverse event: 5% Due to GI symptoms: NR GI event frequency: 62%	Fair
					Placebo	-1.8 kg

						> 5% Loss:
					Orlistat	39.0%	23.3%	0.008
					Placebo	15.7%

						> 10% Loss:
					Orlistat	14.1%	10.2%	0.003
					Placebo	3.9%
Karhunen et al, 2000⁹³	120 mg tid	D All participants: dietary advice (-600 kcal/day) individualized advice throughout the 1 yr loss phase	N: 96 Race: NR Female: 82% Age: 43 yrs 35.9 kg/m²	2 yrs: 1 yr of L 1 yr of M	Loss phase	Yr 1			No data on adverse effects Dropout: 24/96 (25%) Due to adverse event: NR	Fair
					Orlistat	-13.1 kg	-4.5 kg	0.007
					Placebo	-8.6 kg

					Maintenance phase
					(Tx Yr 1/Tx Yr 2)	Yr 2 only
					Orlistat/Orlistat	3.1 kg
					Orlistat/Placebo	6.3 kg
					Placebo/Orlistat	0.5 kg
					Placebo/Placebo	3.5 kg
Hill et al, 1999⁹²	30, 60, or 120 mg 3 times daily	D, E, B All participants: 4180 kJ/day deficit diet Multi-vitamin	N: 729 White: 88 Black: 6% Hispanic: 5% Other: 1% Female: 84% Orlistat: 30 mg: 47 yrs 60 mg: 46 yrs 120 mg: 46 yrs Placebo: 46 yrs Orlistat: 30 mg: 32.6 kg/m² 60 mg: 32.9 kg/m² 120 mg: 32.8 kg/m² Placebo: 32.8 kg/m²	52 wks M (following 6 mos of L)	Orlistat 30 mg	4.9 kg	0.5 kg	< 0.001	Orlistat 30 mg: Dropout: 47/187 Due to adverse event: 17/187 Orlistat 60 mg: Dropout: 40/173 Due to adverse event: 17/173 Orlistat 120 mg: Dropout: 55/181 Due to adverse event: 27/181 Placebo: Dropout: 50/188 Due to adverse event: 5/188	Fair
					Orlistat 60 mg	3.8 kg	-0.6 kg
					Orlistat 120 mg	2.6 kg	-1.8 kg
					Placebo	4.4 kg
Giugliano et al, 1993⁹⁷	850 mg bid	Counseled to maintain baseline diet and exercise patterns	N: 50 Race: NR Female: 62% Metformin: 60 yrs Placebo: 60.8 yrs Metformin: 33 kg/m² Placebo: 32.7 kg/m²	6 mos, L	Metformin Placebo	Data in graph form	Data in graph form	NS	NR	Fair
Knowler et al.⁸¹	850 mg bid (titrated up)	D,E Metformin and placebo participants: written information plus annual 20-30 minute individual session emphasizing low-fat diet and physical activity	N: 3234 White: 55% Black: 20% Hispanic: 16% Native American: 5% Asian: 4% Female: 68% Mean: 51 yrs 34 kg/m²	2.8 yrs, L & M	Metformin	-2.1 kg	-2.0 kg	< 0.001	7.5%	Good
					Lifestyle	-5.6 kg	-5.5 kg
					Placebo	-0.1 kg
Mulitple Drugs
Gokcel et al, 2002⁹⁸	Sibutramine: 10 mg bid Orlistat: 120 mg tid Metformin: 850 mg bid	D 25 kcal per kg of ideal body weight with caloric distribution: 50% carbohydrates 30% lipids 20% protein	N: 150 Race: NR Female: 100% Sibutramine: 42.3 yrs Orlistat: 42.1 yrs Metformin: 43.6 yrs Sibutramine: 38.5 kg/m² Orlistat: 35.3 kg/m² Metformin: 37.9 kg/m²	6 mos, L	Sibutramine	-13.4 kg	-4.0 kg 1.0 kg (vs metformin)	BMI loss significantly greater with sibutramine than either other group	Sibutramine: Dropout: NR Due to adverse event: 2/50 Orlistat: Dropout: NR Due to adverse event: 2/50 Metformin: Dropout: NR Due to adverse event: NR	Fair
					Orlistat	-8.0 kg
					Metformin	-9.0 kg
Notes: B = behavioral therapy; bid = twice daily; BMI = body mass index; cont = continuous; D = diet; E = exercise; GI = gastrointestinal; int = intermittent; L = weight loss; M = maintenance of weight loss; NR = not reported; tid = three times daily. ^a Values are means unless otherwise indicated. ^b Presented as baseline mean or range unless otherwise noted. ^c Compared with control unless otherwise noted. ^d P=0.02 vs placebo.

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