Key Facts

Obesity is recognised as a chronic, relapsing disease by most major medical organisations. It is a leading preventable cause of morbidity and mortality in the UK.

Epidemiology

• 28% of UK adults are obese (BMI ≥30)
• 67% are overweight or obese (BMI ≥25)
• Childhood obesity: ~10% of Reception year, ~23% of Year 6 children are obese
• Socioeconomic deprivation is the strongest predictor of obesity prevalence
• UK prevalence has tripled since the 1980s

Aetiology

• Energy imbalance: chronic energy intake exceeding expenditure
• Environmental/behavioural: ultra-processed food, sedentary lifestyle, portion sizes
• Genetic: highly heritable (40-70%); polygenic in most cases
• Monogenic obesity: rare – leptin deficiency, MC4R mutations (most common monogenic cause)
• Endocrine: hypothyroidism, Cushing syndrome, GH deficiency (rare causes)
• Medications: corticosteroids, insulin, sulphonylureas, antipsychotics, antidepressants (mirtazapine, amitriptyline), beta-blockers, sodium valproate

Pathophysiology

• Adipose tissue is a metabolically active endocrine organ
• Excess visceral fat → chronic low-grade inflammation (elevated TNF-α, IL-6, CRP)
• Insulin resistance → type 2 diabetes
• Adipokine dysregulation: elevated leptin (leptin resistance), reduced adiponectin
• Mechanical effects: joint loading, airway compression
• Altered gut microbiome composition in obesity

Metabolic Complications

• Type 2 diabetes (risk increases 7-fold for BMI >30)
• Dyslipidaemia: raised triglycerides, low HDL
• Hypertension
• Non-alcoholic fatty liver disease
• Metabolic syndrome

Cardiovascular

• Coronary artery disease
• Heart failure (both HFrEF and HFpEF)
• Atrial fibrillation
• Venous thromboembolism

Respiratory

• Obstructive sleep apnoea
• Obesity hypoventilation syndrome (Pickwickian syndrome)

Other

• Osteoarthritis (weight-bearing joints)
• GORD
• Depression and anxiety
• Subfertility (anovulation in women, reduced sperm quality in men)
• Cancer: breast, colorectal, endometrial, oesophageal, pancreatic, kidney, and others

Red Flags

• Rapid weight gain → exclude Cushing syndrome, hypothyroidism
• Childhood obesity with learning difficulties → consider Prader-Willi syndrome
• Severe early-onset obesity (<5 years) → consider monogenic causes

Bedside

• BMI: weight (kg) / height² (m²)
• Waist circumference: ≥94cm (men) or ≥80cm (women) indicates central obesity
• Blood pressure
• Epworth Sleepiness Scale: screen for OSA

Bloods

• HbA1c or fasting glucose: screen for diabetes
• Lipid profile: total cholesterol, HDL, LDL, triglycerides
• LFTs: screen for NAFLD
• TFTs: exclude hypothyroidism
• FBC, U&Es: baseline
• Consider: cortisol (if Cushingoid features), fasting insulin (research settings)

Imaging

• Liver ultrasound/FibroScan: if suspected NAFLD
• Sleep study (polysomnography): if OSA symptoms

Special Tests

• QRISK3: cardiovascular risk assessment
• Mood assessment: PHQ-9 for depression screening
• Genetic testing: if severe early-onset obesity or syndromic features

Non-pharmacological

• Lifestyle modification (first-line for all patients):
  • Reduced calorie diet: 600 kcal/day deficit
  • Increased physical activity: 150 min/week moderate intensity, progressing to 300 min/week
  • Behavioural strategies: food diary, cognitive behavioural approaches
  • Very low-calorie diets (800 kcal/day) for 12 weeks under supervision in select patients (NICE NG28 for T2DM remission)

Pharmacological

• Orlistat 120mg TDS with meals (lipase inhibitor – reduces fat absorption by ~30%)
  • NICE: BMI ≥30 (or ≥28 with comorbidities)
  • Side effects: steatorrhoea, faecal urgency
• Semaglutide 2.4mg SC weekly (Wegovy – GLP-1 receptor agonist)
  • STEP trials showed mean weight loss of ~15%
  • NICE approved for BMI ≥35 with weight-related comorbidity (or ≥30 with specific criteria)
• Liraglutide 3.0mg SC daily (Saxenda) – alternative GLP-1 RA for weight management
• Tirzepatide (dual GIP/GLP-1 agonist) – SURMOUNT trial: ~20% weight loss

Surgical/Interventional (NICE CG189)

• Bariatric surgery indications:
  • BMI ≥40 (or ≥35 with significant comorbidities)
  • BMI ≥30-34.9 with recent-onset type 2 diabetes (as per NICE NG28)
  • Lower BMI thresholds for South Asian patients
• Procedures:
  • Roux-en-Y gastric bypass: gold standard, 25-30% weight loss
  • Sleeve gastrectomy: 20-25% weight loss, most commonly performed
  • Adjustable gastric band: 15-20% weight loss (declining use)
  • One anastomosis gastric bypass (OAGB): emerging option
• Post-operative: lifelong nutritional supplementation (iron, B12, folate, calcium, vitamin D), dietetic follow-up

Referral Criteria

• BMI ≥40 (or ≥35 with comorbidities) → bariatric surgery assessment (NICE CG189)
• Suspected endocrine cause → endocrinology
• Childhood obesity with dysmorphic features → genetics
• Disordered eating → eating disorders service

• Obesity reduces life expectancy by 2-4 years (BMI 30-35) or 8-14 years (BMI >40)
• 5-10% weight loss reduces diabetes risk by 58% (DPP trial), improves BP, lipids
• Bariatric surgery: >50% achieve and maintain >20% weight loss at 5 years
• Type 2 diabetes remission after bariatric surgery: 50-80% at 2 years (SOS study)
• Weight regain is common after lifestyle interventions alone (~50% regain by 2 years)
• GLP-1 receptor agonists show sustained weight loss while continued, with regain on cessation

BMI Classification (WHO, with NICE adjustments)

Landmark Trials in Obesity