Trial	Measured BMI	Adverse events	Health‐related quality of life and self‐esteem	All‐cause mortality	Morbidity
Atabek 2008	Expressed as BMI (kg/m2). Obesity defined as ≥ the 95th percentile for age and sex based on the standards of the CDC (IO)	Participants were asked to report any adverse effects every month. Serious adverse events defined as vomiting or lactic acidosis (SO)	N/I	N/I	Hyperinsulinaemia was defined from norms for pubertal stages 2 to 4: mid‐puberty > 30 mU/L, and postpubertal hyperinsulinism was defined by adult WHO criteria (> 20 mU/L). Insulin sensitivity was estimated using FGIR, HOMA‐IR and QUICKI (IO)
Berkowitz 2003	The change in raw BMI is not given. Instead it is expressed as % reduction in BMI (kg/m2). BMI also used to calculate BMI z score (calculated using CDC standards) Obesity defined as BMI 32 to 44 kg/m2 (IO)	Adverse events were recorded at each medical visit. In addition, blood pressure and heart rate were monitored closely, and any abnormalities were considered as adverse events. A serious adverse event was not defined (AO, IO, SO)	N/I	N/I	N/I
Berkowitz 2006	Expressed as BMI (kg/m2) in graphical format and % change in BMI in text and tabular format. Used Rosner 1998 to define obesity (IO)	The investigator recorded all adverse events, both observed and volunteered. The only serious event defined as excessive nausea and vomiting. Unclear whether suicide attempt and depression were defined as serious (AO, IO, SO)	N/I	2 suicide attempts ‐ did not result in mortality (AO, IO)	N/I
Chanoine 2005	Expressed as BMI (kg/m2). Used Barlow 1998 to define obesity (IO)	Gastrointestinal tract adverse effects assessed at each visit by a specially designed dictionary of standard terms for defecation patterns for reproducibility and consistency of reporting. Other adverse events were noted and followed by questioning. Serious adverse events included acute demyelinating encephalomyelitis, facial palsy, pneumonia, worsening of asthma, pain in the right side, pilonidal abscess, depression, asthma attack, seizure, admission for repair of deviated nasal septum, appendicitis, cholelithiasis, gallbladder disorder followed by cholecystectomy, adenoidal hypertrophy and aseptic meningitis. The trial also used electrocardiograms to detect abnormalities and measured gallbladder ultrasounds to detect gallstones (AO, IO, SO)	N/I	N/I	Gallstones and fatty liver infiltration or hepatomegaly identified by gallbladder ultrasound (IO)
Clarson 2009	Expressed as BMI (kg/m2). Obesity defined as BMI > 95th percentile for age and sex (no reference). BMI z scores calculated using the CDC reference data (IO)	No adverse events reported, trial highlights that metformin was well tolerated by all participants ‐ unclear how this was assessed	N/I	N/I	Insulin resistance was defined using HOMA > 3 (IO)
Franco 2014	Weight and height used to calculate BMI. Obesity defined by WHO classification (IO)	Adverse effects were investigated on a preset questionnaire and described voluntarily by the participant at each consultation (on average every 40 days). A serious adverse event was not defined (AO, SO)	N/I	N/I	N/I
Freemark 2001	Expressed change in BMI. Also expressed as BMI SDS. Used Rosner 1998 to adjusting for age, sex and race (IO)	Unclear how and when adverse events were assessed	N/I	N/I	Hyperinsulinaemia defined as fasting insulin concentration exceeding 15 μU/mL. Insulin sensitivity assessed by fasting insulin‐to‐glucose concentration ratio, QUICKI and HOMA‐IR (IO)
Garcia‐Morales 2006	Expressed as BMI (kg/m2). Used CDC growth charts (Kuczmarski 2000) (IO)	Adverse events were reported as they were detected by the participant or investigator. They were also assessed during visits. Severe adverse events defined as life‐threatening or those resulting in hospitalisation or producing long‐term disabilities (AO, IO, SO)	Health‐related quality of life assessed by a 36‐item Short‐Form Health Survey (SF‐36) questionnaire (Alonso 1995) (SO)	N/I	Comorbidities were accessed at baseline and follow‐up. These included high blood pressure, high glucose, high triglycerides, high cholesterol, high LDL and high HDL (IO)
Godoy‐Matos 2005	Expressed as BMI (kg/m2). Obesity defined as BMI between 30 and 45 (no reference) (IO)	Adverse events were assessed and recorded at each visit. A significant event was defined as a serious or rare event ‐ serious event not defined (AO, IO, SO)	N/I	N/I	N/I
Kendall 2013	Expressed as BMI (kg/m2). Obesity defined by UK BMI centile charts. No reference for how BMI SDS was calculated (IO)	How and when trial authors assessed adverse events was not described. No explanation to how they defined a severe/series event	N/I	N/I	Participants had hyperinsulinaemia, impaired fasting glucose or impaired glucose tolerance Insulin resistance/sensitivity was assessed using: HOMA‐IR, QUICKI, whole‐body insulin sensitivity index, adiponectin‐to‐leptin ratio (IO)
Maahs 2006	Expressed as BMI (kg/m2). Obesity defined as BMI that exceeded the 85th percentile for age and sex (assume this from the CDC standards) (IO)	Adverse events assessed at each monthly visit. Serious/severe adverse events not defined (AO, IO, SO)	Health‐related quality of life assessed by 4 questionnaires: Brief Symptom Inventory (Derogatis 1983), Parents and Children's KINDL (Ravens‐Sieberer 2001), IWQOL‐Kids (Kolotkin 1997; Kolotkin 2001), and a global ratings scale (SO)	Defined as suicide ‐ 1 participant in the orlistat group (AO, IO)	N/I
Mauras 2012	Expressed as BMI (kg/m2). BMI % determined using CDC standards (Kuczmarski 2000) (IO)	Trial authors did not describe how and when adverse events were assessed. Did not report number or type of adverse events	N/I	N/I	Elevated hsCRP and fibrogen concentrations were measured by immuno‐nephelometry (IO)
NCT00001723	BMI SDS calculated for age and sex according to CDC standards (IO)	Events were collected by systematic assessment. Trial authors did not define what a serious adverse event was (IO, SO)	N/I	N/I	N/I
Ozkan 2004	Expressed as BMI (kg/m2). Severe obesity defined as weight for height index > 140% (no reference) (IO)	Unclear how and when adverse events were assessed. All with mild gastrointestinal complaints apart from 2 (mild diffuse hair loss and another with muscle cramps). A serious/severe event was not defined	N/I	N/I	N/I
Prado 2012	Expressed as BMI (kg/m2). Obesity defined as BMI > 95th percentile for age and sex (no reference) (IO)	Adverse events monitored by ALT, AST and haemoglobin levels (IO)	N/I	N/I	Risk factors for diabetes mellitus type 2: high glycaemia fasting, high postload glucose or high insulin sensitivity. Insulin sensitivity accessed by HOMA
Rezvanian 2010	Expressed as BMI (kg/m2). Gave baseline BMI SDS (calculated using revised CDC growth charts: Kuczmarski 2000 but did not give follow‐up measurements (IO)	Participants and parents educated on possible signs of symptoms of hypoglycaemia. They were also given a 24‐hour mobile phone number to call if any adverse events occurred. No definition of severe/serious adverse events (SO)	N/I	N/I	N/I
Srinivasan 2006	Raw BMI (kg/m2) data not provided BMI z score (presented only on a graph) was calculated from the CDC reference data 2000. Obesity defined by the International Obesity Task Force (Cole 2000) (IO)	Unclear how and when adverse events were assessed. No definition for serious/severe events	N/I	N/I	Clinical suspicion of insulin resistance defined by fasting insulin‐to‐glucose ratio or presence of acanthosis nigricans (assessed by severity at the neck by a validated scale) Insulin sensitivity was accessed by SI clamp (minimal model), fasting insulin and fasting glucose (IO)
Van Mil 2007	Expressed as BMI (kg/m2). BMI SDS was determined using the Dutch age‐ and sex‐adjusted BMI curves (Hansen 1998). Obesity defined as ≥ 97th percentile (no reference) (IO)	Adverse events were determined at each visit. Heart rate, DBP, SBP were monitored throughout the trial. No definition of a serious/severe event (AO, IO, SO)	N/I	N/I	N/I
Wiegand 2010	Expressed as BMI (kg/m2) ‐ reference: Park 2009. Also provided BMI SDS, no reference (IO)	Adverse events determined at the 3‐month and 6‐month visit by a clinical and biochemical assessment. No definition of a serious/severe event (AO, IO, SO)	N/I	N/I	Risk factors for type 2 diabetes: acanthosis nigricans, signs of metabolic syndrome and impaired fasting glucose Insulin sensitivity was assessed by HOMA‐IR and insulin sensitivity index (IO)
Wilson 2010	Expressed as BMI (kg/m2). Used CDC charts to convert BMI to BMI z score (Kuczmarski 2000) (IO)	Adverse events assessed at each visit. An appendectomy was defined as a serious/severe event (AO, IO, SO)	N/I	N/I	N/I
Yanovski 2011	Expressed as BMI (kg/m2). Also expressed as BMI SDS (no reference) (IO)	Adverse events accessed at each visit and by laboratory analysis. A serious/severe event was not defined (AO, IO, SO)	N/I	N/I	Insulin sensitivity was calculated (from a SI clamp) using the metabolic rate‐to‐steady‐state insulin ratio. Insulin resistance estimated using HOMA‐IR (IO)
aIn addition to definition of endpoint measurement, description who measured the outcome (AO: adjudicated outcome measurement; IO: investigator‐assessed outcome measurement; SO: self‐reported outcome measurement). ALT: alanine transaminase; AST: aspartate transaminase; BMI: body mass index; BMI SDS: body mass index standard deviation score; CDC: Centers for Disease Control and Prevention; DBP: diastolic blood pressure; FGIR: fasting insulin concentration/fasting glucose concentration; HbA1c: glycosylated haemoglobin A1c; HDL: high‐density lipoprotein; HOMA(‐IR): homeostasis model assessment (insulin resistance); hsCRP: high sensitivity C‐reactive protein; IWQOL: Impact of Weight on Quality of Life questionnaire; LDL: low‐density lipoprotein; N/I: not investigated; OGTT: oral glucose tolerance test; QUICKI: quantitative insulin check index; SBP: systolic blood pressure; SI clamp: insulin sensitivity clamp; WHO: World Health Organization.