Intensive Weight Loss Intervention Versus Usual Care for Adults With Obesity

Weight (kg)

Proportion of participants with weight loss ≥20%

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

4-metre gait speed (m/s)

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

Proportion of participants that experienced at least one serious adverse event (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 30 Second Sit to Stand test

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

Sleep duration using SENS Motion accelerometers (hours/day)

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

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)

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), 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 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)