Overview

Obesity Management

1. Clinical Overview

Summary

Obesity is a complex, chronic, relapsing disease defined by excessive fat accumulation (Body Mass Index ≥30 kg/m²) that presents a risk to health. It is a major driver of non-communicable diseases, including Type 2 Diabetes, cardiovascular disease, and cancer. Pathophysiology involves disregulation of appetite control pathways (leptin/ghrelin/GLP-1) and energy balance, rather than simply a lack of willpower. Management follows a tiered approach: Tier 2 (Lifestyle), Tier 3 (Pharmacotherapy including GLP-1 analogues), and Tier 4 (Bariatric Surgery). The emergence of highly effective incretin-based therapies (Semaglutide, Tirzepatide) has revolutionised medical management. [1,2]

Key Facts

Definition: BMI ≥30 kg/m² (Obese), 25-29.9 (Overweight). Lower thresholds for Asian populations (≥27.5 and ≥23).
Waist Circumference: Better predictor of visceral fat and metabolic risk than BMI alone. High risk: Men >102cm, Women >88cm.
Tiers of Care:
- Tier 1: Public health prevention.
- Tier 2: Primary care lifestyle intervention.
- Tier 3: Specialist weight management (Pharmacotherapy).
- Tier 4: Bariatric surgery.
GLP-1 Analogues: Semaglutide (Wegovy) induces ~15% weight loss; Tirzepatide (Mounjaro) ~20%.
Surgery: Most effective long-term treatment, inducing remission of T2DM in >60% of cases.

Clinical Pearls

Obesity is a Disease: Recognise obesity as a physiological dysfunction of energy regulation (Set Point Theory), not a moral failing. Hormonal adaptations (reduced leptin, increased ghrelin) fight against weight loss, causing "yo-yo" regain.

The "Obesity Paradox": In some chronic conditions (e.g., heart failure, dialysis), higher BMI is associated with better survival, possibly due to nutritional reserve ("reverse epidemiology").

Prescribing by Weight: Many drugs (e.g., antibiotics, anticoagulants) may need dose adjustment in obesity. Conversely, fixed doses may be sub-therapeutic.

Orlistat: The "educational" side effects (oily spotting, urgent diarrhoea) only occur if the patient eats fat. It enforces a low-fat diet through negative reinforcement.

2. Epidemiology

Incidence

Global Pandemic: Worldwide obesity has nearly tripled since 1975.
UK Prevalence: ~28% of adults are obese; ~36% overweight.
Children: 20% of Year 6 children (aged 10-11) in UK are obese.

Comorbidities (The "4 Ms")

Category	Conditions
Metabolic	Type 2 Diabetes, Hypertension, Dyslipidaemia, Gout, Fatty Liver (MASLD), PCOS, Infertility.
Mechanical	Osteoarthritis (Knee/Hip/Back), Obstructive Sleep Apnoea (OSA), Gastro-oesophageal Reflux (GORD).
Mental	Depression, Anxiety, Low self-esteem, Stigma.
Malignant	Increased risk of Oesophageal, Colorectal, Breast, Endometrial, and Renal cancers.

3. Pathophysiology

Regulation of Energy Balance

Hypothalamus (Arcuate Nucleus): Central control centre.
Orexigenic (Hunger): NPY/AgRP neurons. Stimulated by Ghrelin (from stomach).
Anorexigenic (Satiety): POMC/CART neurons. Stimulated by Leptin (adipose), GLP-1/PYY (gut), Insulin (pancreas).

Dysregulation in Obesity

Leptin Resistance: High fat mass = High leptin. The brain stops responding to the "full" signal.
Gut Dysbiosis: Altered microbiome extracts more energy from food.
Adiposopathy: "Sick fat". Adipocytes release inflammatory cytokines (TNF-α, IL-6) → Insulin Resistance and systemic inflammation.

4. Clinical Presentation

Assessment

Red Flags (Secondary Causes)

History

Weight trajectory, dietary habits (be non-judgemental), physical activity, sleep, stress.

Review of Systems

Snoring (OSA), Joint pain (OA), Menstrual irregularity (PCOS).

Medications

Check for obesogenic drugs (Steroids, Atypical Antipsychotics, Sulfonylureas, Sodium Valproate, Beta-blockers).

5. Clinical Examination

Measurements

BMI: Weight (kg) / Height (m)².
Waist Circumference: Measure at midpoint between iliac crest and lowest rib.
Blood Pressure: Use appropriate large cuff to avoid false elevation.

Signs of Comorbidities

Acanthosis Nigricans: Dark velvety patches (neck/axilla) → Insulin Resistance.
Hirsutism: PCOS.
Hepatomegaly: Fatty liver.
Dependent Oedema: Heart failure or venous insufficiency.

6. Investigations

Routine Panel

HbA1c / Fasting Glucose: Screen for Pre-diabetes/Diabetes.
Lipid Profile: Dyslipidaemia.
Liver Function Tests: ALT/AST/GGT (Screen for MASLD).
Thyroid Function: TSH.

Selected Investigations

Sleep Studies: If OSA suspected (STOP-Bang score).
Echocardiogram: If heart failure suspected.
Dexa Scan: Bone density (can be difficult in severe obesity).

7. Management

Management Algorithm

           BMI ASSESSMENT
                ↓
    ┌───────────┼───────────┐
  25-29.9     30-34.9     35-39.9      ≥40
(Overweight)  (Obesity I) (Obesity II) (Obesity III)
    ↓           ↓           ↓           ↓
 TIER 1/2    TIER 2      TIER 3      TIER 3/4
(Lifestyle) (Lifestyle) (Specialist) (Surgery)
                            +           +
                        Drugs if    Consider if
                        comorbid    BMI &gt;35+
                                    comorbid

Tier 1 & 2: Lifestyle Interventions

Diet:
- Calorie deficit (e.g., -600 kcal/day) is key.
- Approaches: Low Carb, Low Fat, Mediterranean, Meal Replacement. (Adherence matters more than type).
Activity:
- 150 mins moderate activity/week (prevention).
- 300 mins/week often needed for weight loss.
Behavioural: Support groups, goal setting, self-monitoring.

Tier 3: Pharmacotherapy

Criteria: BMI ≥30, or ≥27 with comorbidities.

GLP-1 Receptor Agonists (s.c. injection)
- Liraglutide (Saxenda): Daily. ~5-8% loss.
- Semaglutide (Wegovy): Weekly. ~15% loss.
- Mechanism: Delays gastric emptying, acts on hypothalamus to increase satiety.
- Side Effects: Nausea, vomiting, diarrhoea (usually transient). Risk of pancreatitis/gallstones.
Dual Agonists (GLP-1 / GIP)
- Tirzepatide (Mounjaro): Weekly. ~20-22% loss. Superior to Semaglutide in head-to-head.
Orlistat (Xenical)
- Mechanism: Pancreatic lipase inhibitor. Blocks ~30% fat absorption.
- Side Effects: Steatorrhoea, faecal urgency/incontinence if high fat intake.
- Role: Second line / lower cost option.
Mysimba (Naltrexone/Bupropion): Central appetite suppressant. Moderate efficacy.

Tier 4: Bariatric Surgery

Criteria (NICE): BMI ≥40, or 35-40 with significant comorbidity (T2DM, BP). rapid access if BMI >35 + recent onset T2DM.

Procedure	Mechanism	Weight Loss	Remission T2DM
Roux-en-Y Bypass	Restrictive + Malabsorptive	60-70% EWL	~80%
Sleeve Gastrectomy	Restrictive + Hormonal (Ghrelin↓)	50-60% EWL	~60%
Gastric Band	Restrictive (Adjustable)	40-50% EWL	Lower

EWL = Excess Weight Loss.

8. Complications

Surgical Complications

Dumpings Syndrome (Bypass): Hypoglycaemia/diarrhoea after sugar intake.
Nutritional Deficiencies: Iron, B12, Calcium, Folate. Requires lifelong supplementation.
Internal Hernia (Bypass risk).

Disease Complications

See "4 Ms" epidemiology.
Pickwickian Syndrome: Obesity Hypoventilation Syndrome.

9. Prognosis and Outcomes

Sustainability

Lifestyle: Only 5-10% maintain significant weight loss at 5 years.
GLP-1s: Highly effective while taken. Rebound weight gain is common upon cessation (chronic disease needing chronic treatment).
Surgery: Most durable option, but 20-30% regain some weight long-term.

Mortality Benefit

Bariatric surgery reduces all-cause mortality, primarily by reducing cardiovascular death and cancer.

10. Evidence and Guidelines

Key Guidelines

Guideline	Organisation	Key Recommendations
CG189	NICE (2014, updated)	Tiers of care. Surgical criteria.
TA875	NICE (2023)	Semaglutide recommended for BMI ≥35 (or ≥30 with special criteria) for max 2 years.
Obesity Management	Endocrine Society	Escalation to pharmacotherapy/surgery for non-responders.

Landmark Studies

1. STEP Trials (Semaglutide Treatment Effect in People with obesity) [3]

STEP 1: Semaglutide 2.4mg vs Placebo.
Result: -14.9% weight loss vs -2.4%.
Impact: Established Semaglutide as game-changer.

2. SURMOUNT-1 (Tirzepatide) [4]

Result: Up to 22.5% weight loss with 15mg dose.
Impact: Efficacy approaching surgical levels.

3. SOS Study (Swedish Obese Subjects)

Result: Bariatric surgery reduced long-term mortality (29% reduction) and diabetes incidence compared to matched controls over 20 years.

11. Patient and Layperson Explanation

Why is losing weight so hard?

It is not your fault. Your body has a "set point" for weight. When you diet, your body thinks it is starving: it hormones make you hungrier and slow down your metabolism to protect your fat stores. This is why "eat less, move more" often fails in the long run.

Treatments available

Lifestyle: Healthy changes are the foundation, but often need help.
Injections (Wegovy/Saxenda): These copy a natural hormone that tells your brain "I'm full". They are very effective at turning down the "food noise" in your head.
Surgery: For severe obesity, surgery changes your stomach size and hormones. It is a major operation but has the best long-term results and can cure diabetes.

Does it matter?

Yes. Losing just 5-10% of your body weight (e.g., 10kg if you are 100kg) massively improves your health. It lowers blood pressure, improves diabetes, and reduces joint pain. You don't need to be "skinny" to be healthy.

12. References

Primary Sources

NICE Guideline CG189. Obesity: identification, assessment and management. 2014.
Rubino F, et al. Joint International Consensus Statement for Ending Stigma of Obesity. Nat Med. 2020;26:485-497.
Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384:989-1002.
Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387:205-216.
Sjöström L. Review of the key results from the Swedish Obese Subjects (SOS) trial - a prospective controlled intervention study of bariatric surgery. J Intern Med. 2013;273:219-234.

13. Examination Focus

Common Exam Questions

Surgery: "A 45-year-old man with BMI 42 and T2DM requests surgery. Does he qualify?"
- Answer: Yes. NICE criteria BMI ≥40 alone, or BMI 35-40 with comorbidity.
Pharmacology: "Mechanism of Orlistat?"
- Answer: Gastric and Pancreatic Lipase Inhibitor.
Endocrinology: "Patient on Liraglutide develops severe abdominal pain and vomiting. Diagnosis?"
- Answer: Acute Pancreatitis (rare but serious side effect).
Paediatrics: "Syndromic cause of obesity with hyperphagia?"
- Answer: Prader-Willi Syndrome.

Viva Points

GLP-1 mechanism: Central satiety + Delayed gastric emptying.
Nutritional deficiency post-bypass: Need B12 (lost intrinsic factor), Iron, Calcium, Vit D.
Metabolic Surgery: The concept that surgery works via hormonal changes (incretins) not just restriction.

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.