Table 1. Randomized controlled trials of the most widely-studied and commonly-used obesity medications in youth.

Population	Dose	Study Length and Design	Weight Loss a	Attrition	Side Effects	Cost / Month b	Reference
Metformin
9 - 18 yr old; Obese; IR n = 12 (drug) ; n = 14 (placebo)	500 mg (2× / day)	3 months; RCT; DBPC	Δ BMI = -0.01 kg/m2	16.2%	None different than placebo	$42.23	(38)
10 - 16 yr old; Obese n = 41 (drug) ; n = 42 (placebo)	500 mg (3× / day)	12 weeks; RCT; DBPC	Δ BMI = -0.60 kg/m2 Δ waist circumference = -1.7 cm	8.9%	Gastrointestinal discomfort and loose stool	$63.34	(39)
13 - 18 yr old; Obese; NGT n = 15 (drug); n = 12 (placebo)	500 mg (3× / day)	4 months; RCT; DBPC	Δ BMI = -2.0 kg/m2 Δ body weight = -3.9 kg	18.0%	Gastrointestinal and stomach discomfort	$63.34	(40)
12 - 19 yr old; Obese n = 14 (drug) ; n = 17 (placebo)	500 mg (2× / day)	6 months; RCT; DBPC	Δ BMI = -0.73 kg/m2	10.4%	Mild abdominal discomfort and diarrhea	$42.23	(41)
12 - 19 yr old; Obese; IR n = 60 (drug) ; n = 25 (placebo)	850 mg (2× / day) C	6 months; RCT; DBPC	Δ BMI = -0.79 kg/m2	24.0%	Gastrointestinal discomfort	$72.00	(42)
9 - 18 yr old; Obese n = 28 (randomized)	1000 mg (2× / day)	6 months; RCT; DBPC; Crossover	Δ BMI = -1.26 kg/m2 Δ BMI Z-score = -0.12	21.5%	None different than placebo	$86.41	(43)
10 - 17 yr old; Obese n = 36 (drug) ; n = 34 (placebo)	500 mg (2× / day)	6 months; RCT; DBPC	Δ BMI = +0.38 kg/m2	10.0%	None different than placebo	$42.23	(44)
6 - 12 yr old; Severe Obesity; IR n = 53 (drug); n = 47 (placebo)	1000 mg (2× / day)	6 months; RCT; DBPC	Δ BMI = -1.09 kg/m2 Δ BMI Z-score = -0.07	15.0%	Gastrointestinal discomfort	$86.41	(45)
8 - 17 yr old; Obese; NAFLD n = 57 (drug); n = 58 (placebo)	500 mg (2× / day)	96 weeks; RCT; DBPC	Δ BMI = -0.60 kg/m2 Δ BMI Z-score = -0.06	13.1%	None different than placebo	$42.23	(46)
13 - 18 yr old; Obese n = 39 (drug); n = 38 (placebo)	XR 2000 mg (1× / day)	52 weeks; RCT; DBPC	Δ BMI = -1.10 kg/m2 Δ BMI Z-score = -0.08	26.0%	None different than placebo	$89.40	(47)
8 - 18 yr old; Obese; IFG or IGT n = 74 (drug); n = 77 (placebo)	500 / 1000 mg (2× / day)d	6 months; RCT; DBPC	Δ BMI = -1.07 kg/m2 Δ BMI Z-score = -0.1	27.0%	Gastrointestinal discomfort	$64.33	(19)
7 - 18 yr old; Obese; NGT n = 35 (drug + lifestyle); n = 31 (lifestyle)	Up to 1000 mg (2× / day) e	6 months; RCT; Open Label	Δ BMI = -1.30 kg/m2 Δ body weight = -3.2 kg	36.0%	None different than placebo	$86.41	(18)
Orlistat
14 - 18 yr old; Overweight n = 20 (drug); n = 20 (placebo)	120 mg (3× / day)	6 months; RCT; DBPC	Δ BMI = -0.50 kg/m2	15.0%	Soft stools, oily spotting, oily evacuation, liquid stools	$614.53	(48)
12 - 16 yr old; Obesity n = 357 (drug); n = 182 (placebo)	120 mg (3× / day)	6 months; RCT; DBPC	Δ BMI = -0.86 kg/m2 Δ waist circumference = -1.45 cm	3.6%	Gastrointestinal discomfort, oily spotting, oily evacuation	$614.53	(28)
Exenatide
12 - 19 year old; Severe Obesity n = 12 (drug); n = 10 (placebo)	10 μg (2× / day) f	3 months; RCT; DBPC	% change in BMI = - 2.70% Δ body weight = -3.26 kg	15.0%	Mild: Nausea, abdominal pain, diarrhea, headache, vomiting.	$619.93	(20)
8 - 19 year old; Severe Obesity n = 12 (randomized)	10 μg (2× / day) f	6 months; Randomized, Crossover Open Label	% change in BMI = - 4.92% Δ body weight = -3.90 kg	8.3%	Mild: nausea, vomiting, headache, and abdominal pain	$619.93	(49)

Abbreviations (order of appearance): IR = insulin resistance; RCT = randomized controlled trial; DBPC = double-blind, placebo-controlled; BMI = body mass index; NGT = normal glucose tolerance; NAFLD = non-alcoholic fatty liver disease; XR = extended release; IFG = impaired fasting glucose; IGT = impaired glucose tolerance

^A: Weight-loss is placebo/control-subtracted unless otherwise noted.

^B: Cost / Month is reflective of average wholesale price (AWP) plus dispensing fees.

^C: Started at 500 mg once daily. At 1 month, the dose increased to 500 mg twice daily, followed by an increase to 850 mg twice daily at 2 months.

^D: 1000 mg taken 1× / day in the morning, 500 mg taken 1× / day in the evening.

^E: Initiated at a dose of 250mg (2× / day), then increased to 500 mg (2× / day) and if older than 12 increased to 1000 mg (2×/day) if tolerated.

^F: Initiated at a dose of 5 μg, subcutaneously, twice per day. After 1 month, exenatide was uptitrated to 10 μg twice per day for the remaining 2 months.