Intensive Weight Loss Intervention Versus Bariatric Surgery for Adults With Severe and Complex Obesity: the LightBAR Randomised Trial

Metabolic syndrome severity Z-score

Weight (kg)

4-metre gait speed (m/s)

Quality of life, SF36-mental component score (scale from 0-100, higher scores indicate better mental health)

Proportion of participants with at least one serious adverse event (according to ICH-GCP guidelines)

• Anaemia (haemoglobin <6.8 mmol/L (<110 g/L))
• Severe and persistent/recurrent gastrointestinal symptoms (i.e.: reflux, nausea/vomiting, constipation, diarrhoea, abdominal pain - defined according to a modification of Rome IV criteria).
• Symptomatic hypotension (episode with loss of consciousness, seizures, or other severe mental impairments due to suspected orthostatic hypotension).
• Hypoglycaemia (episode with loss of consciousness, seizures or other severe mental impairments requiring third party assistance (level 3) or documented glucose concentration <3.0 mmol/l (level 2) or initiation of medication related to documented reactive hypoglycaemia).
• Incident alcohol abuse, other addictive disorder, self-inflicted harm, or eating disorders (Initiation of treatment (behavioural or pharmacological) for addictive disorders or documented self-inflicted harm not requiring hospitalisation (outpatient visits to emergency rooms, GP etc).

Proportion of participants with metabolic syndrome

Systolic and diastolic blood pressure (mmHg)

Pulse rate (beats per minute)

Fasting glucose concentration (mmol/l)

Haemoglobin A1c (mmol/mol)

Fasting insulin concentration (pmol/L)

HOMA2-IR (calculated from glucose and C-peptide concentration) (ratio)

Fasting lipid profile (HDL, LDL and triglycerides) (mmol/L)

Estimated Glomerular Filtration Rate (eGFR), creatinine (µmol/L), calculated from creatinine, sex and years

High-sensitivity C-reactive protein (hsCRP), mg/L

Fib-4 (ALT/AST/platelets) (ratio)

Proteinuria, measured as urine albumin/creatinine (ratio)

Thyroid-stimulating hormone (IU/L)

Proportion of participants with body weight loss of ≥20% and ≥15%

Waist circumference (cm)

Body fat (%) and lean body mass (%) assessed by DXA

Time spent sedentary and active (moderate to vigorous physical activity) estimated by SENS activity tracker (minutes/day)

Number of sit to stands completed 30 Second Sit to Stand test

• Glucose-lowering medications (number, type)
• Lipid-lowering medications (number, type)
• Blood pressure-lowering medications (number, type)
• Medication for pain relief (number, type)
• Weight loss medication (number, type)
• Medication used for psychiatric disorders (antidepressants, anxiolytics, antipsychotics) (number, type)

• Iron
• B12
• Folate
• Vitamin D
• Hyperparathyroidism

• BMD of weight bearing regions: hip (total hip and femoral neck) and lumbar region
• BMD of non-weight bearing region: forearm of non-dominant hand (ultradistal and 1/3 distal radius)

Epworth Sleepiness Scale Questionnaire Score (scale from 0-24, higher scores indicate more sleepiness)

Estimated sleep and wake time (minutes/day)

Movement during sleep estimated by SENS.

EQ-5D-5L, index score (score between -1 and 1, higher scores indicate better health)

EQ-5D-5L, VAS score (scale from 0-100, higher scores indicate better health)

Short-Form-36, physical component score (scale from 0-100, higher scores indicate better physical health)

Eating Disorder Examination Questionnaire (EDE-Q) score (scale from 0 to 6, higher scores indicate higher degree of eating disorder)

Weight Bias Internalization Scale (WBIS-M) score (scale from 1-7, higher scores indicate higher degree of internalised weight bias)

Major Depression Inventory (MDI) (scale from 0-50, higher scores indicate more symptoms of depression)

Work productivity and impairment (WPAI) score points (scale from 0-100, higher scores indicate more limitations in ability to work and lower productivity)

Self-reported number of days sick leave during follow-up

Time spent in level 1 hypoglycaemic range (interstitial fluid glucose (IFG) <3.9 mmol/L)

Number of hypoglycaemic events (15 minutes of IFG<3 mmol/L)

Glucose variability (CV)

Self-reported hypoglycaemic symptoms as recorded in hypoglycaemic symptom diary (reported descriptively)

• Common gene variants with low to moderate effect on the phenotype for the construction of aggregate genetic risk scores
• Rare variants with potential functional effects in genes known to harbour high-impact obesity variants e.g. MC4R, LEP, LEPR, POMC, PCSK1, SIM1, NTRK2, MC3R, MRAP2, BDNF, SH2B1, KSR2

Quality of life (measured using EQ-5D-5L)

24-month costs, DKK

Incremental cost per quality-adjusted-life-year (QALY) gained, DKK

Predicted lifetime QALYs gained

Predicted lifetime healthcare costs, DKK

Long-term incremental cost effectiveness ratios

• Proportion of participants who die from any cause
• Proportion of participants with a major CVD outcome consisting of any of the following (each of the components will be assessed exploratively): myocardial infarction, stroke, hospitalisation for angina, coronary-artery bypass grafting, percutaneous coronary intervention, hospitalisation for heart failure, peripheral vascular disease

• Proportion of participants on glucose-lowering medications
• Proportion of participants on lipid-lowering medications
• Proportion of participants on blood pressure-lowering medications
• Proportion of participants on medication for pain relief
• Proportion of participants on weight loss medication
• Proportion of participants on medication used for psychiatric disorders (antidepressants, anxiolytics, antipsychotics)

• Proportion of participants with any diagnosis of cancer
• Proportion of participants with cancers known to be associated with obesity: GI tract including liver and kidney and reproduction organs (including breast for women and prostate for men)

• Proportion of participants with any surgical procedure related to bariatric surgery: revisional surgery for late complications eg internal hernia, stomal ulcer; and conversion surgery eg change of operation from index procedure to another for weight regain or complications; or new bariatric procedures
• Proportion of participants with surgical procedures related to obesity and/or weight loss: eg cholecystectomy, body contouring surgery, elective arthroplasty

• Proportion of participants with any fracture
• Proportion of participants with major osteoporotic fracture (hip, spine, wrist, humerus)

Employment status each participant

Salary for each participant

Number of absence days

Proportion of participants with any sick leave

Proportion of participants with long-term sick leave (more than 4 weeks continuous sickness absence)