Intensive Weight Loss Intervention Versus Usual Care for Adults With Severe and Complex Obesity

Metabolic syndrome severity Z-score (scale from -4 to 4, mean is 0, higher scores indicate a worse outcome)

Weight (kg)

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

4-metre gait speed (m/s)

Proportion of participants with weight loss ≥20%

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

Proportion of participants with incident eating disorders during the intervention period

• Bone mineral density (g/cm²) of hip (total hip and femoral neck),
• Bone mineral density (g/cm²) of lumbar region

Waist circumference (cm)

• Body fat percentage
• Visceral fat percentage
• Subcutaneous fat percentage

Proportion of participants with weight loss ≥10%

Objectively measured moderate to vigorous physical activity (MVPA) using SENS Motion accelerometers (hours/day)

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

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

Sleep duration using SENS Motion accelerometers (hours/day)

• Proportion of participants prescribed glucose-lowering medications (number, type)
• Proportion of participants prescribed lipid-lowering medications (number, type)
• Proportion of participants prescribed blood pressure-lowering medications (number, type)
• Proportion of participants prescribed medication for pain relief (number, type)
• Proportion of participants prescribed use of medications for psychiatric disorders (number, type)

Systolic and diastolic blood pressure (mmHg)

Pulse rate (beats per minute)

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)

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

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

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

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

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

Quality of life (measured using the 5-level EQ-5D version, EQ-5D-5L VAS score (scale from 0-100, higher scores indicate better health)

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

Employment status for 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)