. 2016 Nov 29;2016(11):CD012436. doi: 10.1002/14651858.CD012436

1. Overview of trial populations.

Trial	Intervention(s) and comparator(s)	Description of power and sample size calculation	Screened/eligible  (N)	Randomised  (N)	Safety  (N)	ITT  (N)	Finishing trial  (N)	Randomised finishing trial  (%)	Follow‐up time^a
Atabek 2008^b	I: metformin + diet and physical activity advice	‐	‐	90	90	‐	90	100	6 months
	C: placebo + diet and physical activity advice	‐	‐	30	30	‐	30	100
	total:			120	120	‐	120	100
Berkowitz 2003	I: behavioural programme + sibutramine	Powered to detect a 4% difference in % change in BMI between the 2 treatment groups with an SD of 5% (α = 0.05, β = 93%)^c	146	43	43	43	40	93.0	6 months (not including the 6‐month open‐label period where all participants received sibutramine)
	C: behavioural programme + placebo		146	39	39	39	34	87.2
	total:			82	82	82	62	75.6
Berkowitz 2006	I: behavioural programme + sibutramine	"Planned sample size was approximately 400 participants with a 3:1 randomization ratio of sibutramine to placebo. On the basis of previous 12‐month adult trials, we determined that 300 participants in the sibutramine group would be adequate to assess safety and exposure, allowing an overall dropout rate of approximately 50% and a probability that approximately 50% of participants receiving 10 mg of sibutramine would lose 10% or more of initial BMI at 6 months" "Although the protocol did not document a formal sample size calculation for efficacy, approximately 132 adolescents (99 in the sibutramine group and 33 in the placebo group) would allow a between‐group difference in BMI of 2 kg/m², with 90% power (2‐sided level of 0.05) to be statistically significant, assuming a common SD of 3 kg/m²)"^d	‐	368	368	‐	281	76.4	12 months
	C: behavioural programme + placebo		‐	130	130	‐	80	61.5
	total:			498	498	‐	361	72.5
Chanoine 2005	I: orlistat + diet + exercise + behaviour therapy	"We planned to enroll at least 450 individuals to provide more than 80% power to detect a difference of 1 BMI unit, assuming a 30% dropout rate"	588	357	352	348	232	65.0	54 weeks
	C: placebo + diet + exercise + behaviour therapy		588	182	181	180	117	64.3
	total:			539	533	528	349	64.7
Clarson 2009	I: metformin + lifestyle intervention	‐	65	14	‐	‐	11	78.6	6 months
	C: lifestyle intervention only	‐	65	17	‐	‐	14	82.4
	total:			31	‐	‐	25	80.6
Franco 2014 (cross‐over trial)	I: sibutramine + dietary guidance	‐	73	‐	‐	‐	‐	‐	13 months
	C: placebo + dietary guidance	‐	73	^‐	‐	‐	‐	‐
	total:			63	63	‐	23	36.5
Freemark 2001	I: metformin	‐	‐	15	‐	‐	14	93.3	6 months
	C: placebo	‐	‐	17	‐	‐	15	88.2
	total:			32	‐	‐	29	90.6
Garcia‐Morales 2006	I: sibutramine + diet + exercise	13 participants per group (expectations: mean loss of 7.5 kg (SD 5.3) in the sibutramine group vs 3.6 kg (SD 4.5) in the placebo group)^e	70	26	26	23	21	80.8	6 months
	C: placebo + diet + exercise		70	25	25	23	19	76.0
	total:			51	51	46	40	78.4
Godoy‐Matos 2005	I: sibutramine + hypocaloric diet + exercise	‐	‐	30	30	30	28	93.3	24 weeks
	C: placebo + hypocaloric diet + exercise	‐	‐	30	30	30	22	73.3
	total:			60	60	60	50	83.3
Kendall 2013	I: metformin + healthy lifestyle advice	"The target recruitment was 140 patients, based on a power calculation using the results of a previous study. A standard power calculation was used to detect a reduction in BMI of 0.15 kg/m² (SD 0.3). Sixty‐four participants in each group give a statistical power of 80% for a t test at the 5% significance level. This was rounded up to allow for some loss to follow‐up but recognizing that adjustment using multifactorial analysis would likely enhance the trial power by an unpredictable amount"^f	234	‐	74	74	55	‐	6 months
	C: placebo + healthy lifestyle advice		234	‐	77	77	55	‐
	total:			155	151	151	110	71.0
Maahs 2006	I: orlistat + diet and exercise therapy	"We determined that a clinically important mean difference in decrease in BMI between the orlistat and placebo groups would be 2.0 kg/m² at 6 months and used an SD of 1.8. On the basis of this approach, a sample size of 15 subjects per group would be adequate to detect a 2.0 kg/m² difference in Student’s t test with 80% power and alpha = 0.05. In order to allow for a 25% dropout rate, 20 subjects were randomized to each group"^g	43	20	‐	20	18	90.0	6 months
	C: placebo + diet and exercise therapy		43	20	‐	20	16	80.0
	total:			40	‐	40	34	85.0
Mauras 2012	I: metformin + diet/exercise intervention	"Differences in hsCRP and fibrinogen concentrations at 6 months were the primary outcomes. An n = 42 completed subjects provided > 90 % power to detect significant changes"	‐	35	35	‐	23	65.7	6 months
	C: diet/exercise intervention		‐	31	31	‐	19	61.3
	total:			66	66	‐	42	63.6
NCT00001723	I: orlistat + behavioural weight loss programme	‐	‐	100	100	100	87	87.0	6 months
	C: placebo + behavioural weight loss programme	‐	‐	100	100	100	84	84.0
				200	100	100	171	85.5
Ozkan 2004	I: conventional treatment (nutritional and lifestyle modification programmes) + orlistat	‐	‐	22	‐	‐	15	68.2	5 to 15 months
	C: conventional treatment: nutritional and lifestyle modification programmes	‐	‐	20	‐	‐	15	75.0
	total:			42	‐	‐	30	71.4
Prado 2012	I: metformin + nutritional guide and exercise programme	8 participants were required per intervention group (SD 0.4; difference of 0.6, P < 0.05, power = 90%)	41/26	‐	9	‐	7	‐	6 months
	C: placebo + nutritional guide and exercise programme		41/26	‐	10	‐	6	‐
	total:			26	19	‐	13	50
Rezvanian 2010	I1: metformin + diet and physical activity advice	"By considering alpha = 0.05 and a power level of 0.8, the sample size was calculated as 160, and by considering the attrition during the follow‐up, we increased it to 180"	180	45	‐	‐	41	91.1	24 weeks
	I2: fluoxetine + diet and physical activity advice			45	‐	‐	40	88.9
	I3: metformin and fluoxetine + diet and physical activity advice			45	‐	‐	41	91.1
	C: placebo + diet and physical activity advice			45	‐	‐	42	93.3
	total:			180	‐	‐	164	91.1
Srinivasan 2006 (cross‐over trial)	I: metformin + "standardised information on healthy eating and exercise"	‐	34	^‐	‐	‐	‐	‐	12 months
	C: placebo + "standardised information on healthy eating and exercise"	‐	34	^‐	‐	‐	‐	‐
	total:			28	‐	‐	22	78.6
Van Mil 2007	I: sibutramine + energy‐restricted diet and exercise plan	"The number of patients required per treatment group to detect a difference between treatment groups in mean change in BMI at endpoint intervention of 1.0 kg/m², based on an estimate of variance (sd) of 0.65, an overall significance level of 5%, and a power of 90%, was nine. Allowing a drop‐out rate of 25%, the number of patients needed in each group was 12"^h	‐	12	12	12	11	91.7	24 weeks
	C: placebo + energy‐restricted diet and exercise plan		‐	12	12	12	9	75.0
	total:			24	24	24	20	83.3
Wiegand 2010	I: metformin + lifestyle intervention	"Since a clinically significant effect was defined as a decrease in HOMA‐IR by ‐1, two groups of 37 patients had to be included in the study to achieve a power of 0.9 with a α value of 0.05"	278	36	‐	‐	34	94.4	6 months
	C: placebo + lifestyle intervention		278	34	‐	‐	29	85.3
	total:			70	‐	‐	63	90
Wilson 2010	I: metformin + lifestyle intervention	"Assuming an SD of 1.9 for BMI change, an enrolled sample of 72 provided 80% power to detect a differential of 1.46 between treatment arms or between sexes and 1.75 between white subjects and others"ⁱ	92	39	39	39	19	48.7	100 weeks
	C: placebo + lifestyle intervention		92	38	38	38	19	50.0
	total:			77	76	76	38	49.4
Yanovski 2011	I: metformin + dietitian‐administered weight‐reduction programme	"A total sample size of 60 participants would detect a between‐group difference of 0.09 BMI SD score units (approximately equivalent to a 2 kg/m² difference) with 80% power. Participant accrual was set at 100 participants to allow as much as 40% loss to follow‐up"^j	278	53	‐	53	45	84.9	6 months (not including the 6‐month open‐label phase)
	C: placebo + dietitian‐administered weight‐reduction programme		278	47	‐	47	40	85.1
	total:			100	‐	100	85	85.0
*Grand total*	*All interventions^k*			*1395*			*1153*
	*All comparators^k*			*817*			*665*
	*All interventions and comparators^k*			*2484*			*1851*

^aDuration of intervention and follow‐up under randomised conditions until end of trial.  ^bUnclear from the publication on the number which completed the trial and hence number of dropouts.  ^cActual treatment difference between intervention groups was 4.5% reduction in BMI.  ^dActual treatment difference between intervention groups at 12 months was 2.9 kg/m².  ^eActual weight loss was 7.3 kg in the sibutramine group vs 4.3 kg in the placebo group.  ^fActual adjusted treatment difference at 6 months was ‐1.07 kg/m².  ^gActual treatment difference between intervention groups at 6 months was 0.5 kg/m².  ^hActual treatment difference between intervention groups at end of intervention (12 weeks) was 0.4 kg/m² and at end of follow‐up (24 weeks) was 1.0 kg/m².  ⁱActual treatment difference between intervention groups after 48 weeks was 1.1 kg/m².  ^jActual treatment difference between intervention groups at 6 months for BMI z score was 0.07.  ^kNumbers for interventions and comparators do not add up to 'all interventions and comparators' because several trials did not provide information on randomised participants per intervention/comparator group but only the total number of randomised participants.

"‐" denotes not reported.

BMI: body mass index; C: comparator; hsCRP: high sensitivity C‐reactive protein; HOMA‐IR: homeostasis model assessment for insulin resistance index; I: intervention; ITT: intention‐to‐treat; n: number of participants; SD: standard deviation.