Trial	Intervention(s) and comparator(s)	Sex (female %)	Age (mean years (SD))	HbA1c (mean % (SD))	BMI (mean kg/m² (SD))	Bodyweight (mean kg (SD))	Comedications/cointerventions	Comorbidities
Atabek 2008	I: metformin + diet and physical activity advice	50	11.8 (2.8)	‐	28.5 (3.4)	67.16 (16.8)	Diet and physical activity advice. Individual consultation sessions with a registered paediatric nutritionist	All participants had hyperinsulinaemia
	C: placebo + diet and physical activity advice	50	11.6 (2.7)	‐	28.0 (3.4)	66.27 (16.9)
Berkowitz 2003	I: behavioural programme + sibutramine	72	14.1 (1.3)	‐	37.5 (4.0)	102 (14.7)	Behavioural therapy	‐
	C: behavioural programme + placebo	62	14.1 (1.2)	‐	38.0 (3.6)	105.3 (16.2)
Berkowitz 2006	I: behavioural therapy programme + sibutramine	66	13.6 (1.3)	‐	35.9 (4.1)	97.9 (14.7)	Behavioural therapy	50.5% had dyslipidaemia, 1.4% had hypertension
	C: behavioural therapy programme + placebo	62	13.7 (1.3)	‐	36.1 (3.8)	97.8 (14.6)		57.4% had dyslipidaemia, 2.3% had hypertension
Chanoine 2005	I: orlistat + diet + exercise + behavioural therapy	65	13.6 (1.3)	‐	35.7 (4.2)	97.7 (15.0)	Behavioural modification + diet + exercise counselling	In the orlistat group, 14 participants had a baseline abnormality revealed by gallbladder ultrasound, including 8 participants with fatty liver infiltration or hepatomegaly and 3 participants with gallstones; 25.3% of participants had the metabolic syndrome at baseline
	C: placebo + diet + exercise + behavioural therapy	71	13.5 (1.2)	‐	35.4 (4.1)	95.1 (14.2)		‐
Clarson 2009	I: metformin + lifestyle intervention	‐	13.1	‐	36.4 (1.8)	‐	Lifestyle intervention	All participants insulin resistant. 15 participants had acanthosis nigricans
	C: lifestyle intervention only	‐	13.1	‐	33.9 (1.1)	‐
Franco 2014	I: sibutramine + dietary guidance	56	13.3 (1.8)	‐	33.9 (7.2)	85.5 (23.2)	Dietary guidance	‐
	C: placebo + dietary guidance		12.3 (1.7)	‐	32.8 (5.8)	83.1 (19.6)
Freemark 2001	I: metformin	79	14.4 (0.6)	5.6 (0.1)	41.5 (0.9)	‐	‐	All participants had fasting hyperinsulinaemia. 8 participants had acanthosis nigricans
	C: placebo	46	15.4 (0.5)	5.5 (0.1)	38.7 (1.3)	‐
Garcia‐Morales 2006	I: sibutramine + diet + exercise	61	15.2 (1.3)	‐	35.1 (5.3)	92.6 (14.6)	Diet and exercise advice	8.7% high blood pressure, 8.7% glucose, 43.5% high triglycerides, 8.7% high cholesterol, 4.3% high LDL, 13% high HDL
	C: placebo + diet + exercise	52	14.7 (1.1)	‐	36.6 (5.2)	98.9 (22.7)		30.4% high blood pressure, 8.7% glucose, 52.2% high triglycerides, 34.8% high cholesterol, 17.4% high LDL
Godoy‐Matos 2005	I: sibutramine + hypocaloric diet + exercise	83	Females: 15.9 (1.1) Males: 16.7 (0.6)	‐	Females: 37.5 (3.8) Males: 37.6 (4.3)	Females: 100.5 (14.2) Males: 117.1 (11.7)	Exercise advice	‐
	C: placebo + hypocaloric diet + exercise	80	Females: 16.3 (1.2) Males: 16.7 (0.6)	‐	Females: 35.8 (4.2) Males: 37.4 (1.9)	Females: 94.0 (13.6) Males: 113.4 (10.0)		‐
Kendall 2013	I: metformin + healthy lifestyle advice	66	13.7 (2.3)	‐	37.1 (6.4)	100.3 (24.1)	Standardised healthy lifestyle advice	All participants had hyperinsulinaemia or impaired fasting glucose or impaired glucose tolerance (or both)
	C: placebo + healthy lifestyle advice	69	13.6 (2.2)	‐	36 (6.3)	96.4 (21.8)
Maahs 2006	I: orlistat + diet and exercise therapy	60	15.8 (1.5)	5.4 (0.1)	39.2 (5.3)	111.1 (22.9)	Dietary and exercise counselling	‐
	C: placebo + diet and exercise therapy	75	15.8 (1.4)	5.4 (0.1)	41.7 (11.7)	114.3 (38.4)		‐
Mauras 2012	I: metformin + diet/exercise intervention	57	12.3 (0.5)	‐	32 (1)	‐	Dietary counselling and free membership to a sports club/gym	Elevated hsCRP or fibrinogen (or both) concentrations
	C: diet/exercise intervention	52	12.0 (0.4)	‐	33.2 (0.7)	‐
NCT00001723	I: orlistat + behavioural weight loss programme	65	14.65 (1.38)	‐	41.7 (0.6)	‐	Behavioural therapy and a multivitamin for 6 months	All participants had at least 1 of the following: systolic or diastolic hypertension (determined by age‐specific charts); frank type 2 diabetes, impaired glucose tolerance assessed by oral glucose tolerance testing; hyperinsulinaemia (defined as a fasting insulin > 15 IU/mL); significant hyperlipidaemia (total cholesterol > 200 mg/dL, LDL cholesterol > 129 mg/dL or fasting triglycerides > 200 mg/dL); hepatic steatosis (ALT or AST above normal range with negative hepatitis studies) or sleep apnoea documented by a sleep trial
	C: placebo + behavioural weight loss programme	66	14.52 (1.46)	‐		‐
Ozkan 2004	I: conventional treatment + orlistat	67	12.9 (2.4)	‐	32.5	82.1 (20.9)	Daily oral multivitamin preparation, lifestyle modification programme	‐
	C: conventional treatment		12.5 (2.2)	‐	31.2	73.9 (15.3)	Lifestyle modification programme	‐
Prado 2012	I: metformin + nutritional guide and exercise programme	100	15.6 (1.9)	‐	33.6	‐	Nutritional guide and exercise programme	30% of participants had psychiatric comorbidities
	C: placebo + nutritional guide and exercise programme	100		‐	33.3	‐		11.1% of participants had psychiatric comorbidities
Rezvanian 2010	I1: metformin + healthy eating and physical activity advice	‐	13.1 (1.4)	‐	26.4 (0.5)	‐	Physical activity advice; nutritional education session and dietary advice	‐
	I2: fluoxetine + healthy eating and physical activity advice	‐	13.5 (1.2)	‐	26.5 (0.7)	‐		‐
	I3: metformin and fluoxetine + healthy eating and physical activity advice	‐	13.7 (1.1)	‐	26.6 (0.8)	‐		‐
	C: placebo + healthy eating and physical activity advice	‐	13.4 (1.4)	‐	26.2 (0.6)	‐		‐
Srinivasan 2006	I: metformin first then placebo + standardised information on healthy eating and exercise	54	12.5 (2.2)	‐	‐	‐	Information on healthy eating and exercise	Suspicion of insulin resistance; 89% participants had acanthosis nigricans
	C: placebo first then metformin + standardised information on healthy eating and exercise			‐	‐	‐
Van Mil 2007	I: sibutramine + energy‐restricted diet and exercise plan	45	14.1 (1.0)	‐	30.1 (4.5)	80.8 (15.6)	Diet and exercise plan	‐
	C: placebo + energy‐restricted diet and exercise plan	58	13.8 (1.5)	‐	33.3 (5.0)	89.2 (16.4)		‐
Wiegand 2010	I: metformin + multiprofessional lifestyle intervention	72	15.1	‐	34.3 (5)	‐	Lifestyle intervention	All had risk factors for developing type 2 diabetes: acanthosis nigricans, signs of the metabolic syndrome, impaired fasting glucose, and positive family history of type 2 diabetes, or with impaired glucose tolerance
	C: placebo + multiprofessional lifestyle intervention	62	15	‐	35.5 (5.8)	‐
Wilson 2010	I: metformin + lifestyle intervention programme	67	14.8 (1.3)	5.4 (0.3)	35.9 (5.7)	95.9 (16.6)	Lifestyle intervention given during run‐in period and follow‐up sessions provided monthly for the remainder of the trial; a multivitamin tablet and calcium carbonate 1000 mg was taken daily	‐
	C: placebo + lifestyle intervention programme	66	15.0 (1.5)	5.3 (0.3)	35.9 (4.7)	101.8 (15.7)		‐
Yanovski 2011	I: metformin + dietitian‐administered weight‐reduction programme	57	10.1 (1.6)	‐	34.2 (6.8)	76.4 (23.1)	A monthly dietitian administered weight‐reduction programme; a daily chewable multivitamin containing cyanocobalamin 6 mg was also prescribed	26.4% had paediatric metabolic syndrome. 64% showed a presence of acanthosis nigricans; all participants had fasting hyperinsulinaemia.
	C: placebo + dietitian‐administered weight‐reduction programme	64	10.4 (1.4)	‐	34.6 (6.2)	80.1 (20.5)		31.9% had paediatric metabolic syndrome. 68% showed a presence of acanthosis nigricans; all participants had fasting hyperinsulinaemia
"‐" denotes not reported. ALT: alanine transaminase; AST: aspartate transaminase; BMI: body mass index; C: comparator; HbA1c: glycosylated haemoglobin A1c; HDL: high‐density lipoprotein; HsCRP: high sensitivity C‐reactive protein; I: intervention; LDL: low‐density lipoprotein; SD: standard deviation.