Obesity Pharmacotherapy
Anti-Obesity Drugs — Incretin Agents (GLP-1 RAs, Tirzepatide), Orlistat, Central Combinations, Setmelanotide & the Withdrawn-Agent Lessons
Past DNB + MPMSU · 3
MPMSUOct '25
DNBDec '13
DNBDec '11
Obesity Pharmacotherapy
1. Definition, scope & rationale for pharmacotherapy
- Obesity is a chronic, relapsing, progressive disease of excess and/or dysfunctional adipose tissue that impairs health; pharmacotherapy is an adjunct to — never a replacement for — lifestyle therapy (medical nutrition therapy, physical activity, behavioural modification) (G&G 14e Ch.51, pp.1031–32; FDA anti-obesity labels [FDA]).
- G&G frames weight loss primarily as a therapeutic goal within type 2 diabetes management ("in type 2 diabetes, lifestyle measures are directed at weight loss") and covers the anti-obesity drug class chiefly where it overlaps the incretin axis; agent-specific indications, dosing and adverse-effect detail draw on the FDA/EMA labels and landmark trials cited throughout (G&G 14e Ch.51, p.1031; FDA labels [FDA]).
- Pharmacotherapy is reserved for patients in whom obesity itself drives morbidity, because all agents carry adverse effects and weight is regained on discontinuation (see §11) — drug therapy is conceived as long-term/chronic, mirroring antihypertensive therapy (FDA labels [FDA]; STEP-4, SURMOUNT-4 [PMID: 33761273]).
- Indian disease burden context: obesity in Asian Indians manifests at lower BMI with greater central/visceral adiposity and cardiometabolic risk than in Western populations; Indian thresholds are accordingly lower (overweight BMI ≥23, obesity ≥25 kg/m2) — the ESI 2025 obesity guideline reframes "overweight" as Grade I obesity (adiposity without organ dysfunction) and Grade II obesity (adiposity with mechanical/metabolic complications) (ESI Clinical Practice Guidelines 2025 [ESI]).
1.1 Indications & BMI thresholds (adjunct to lifestyle)
- Standard (Western, FDA) eligibility for chronic anti-obesity pharmacotherapy: BMI ≥30 kg/m2 (obesity), OR BMI ≥27 kg/m2 (overweight) with ≥1 weight-related comorbidity — e.g. hypertension, type 2 diabetes, dyslipidaemia, obstructive sleep apnoea (OSA), cardiovascular disease (FDA labels: Xenical, Qsymia, Contrave, Saxenda, Wegovy, Zepbound [FDA]).
- Orlistat is additionally approved down to age ≥12 years with the same BMI logic (FDA Xenical label [FDA]).
- Asian-Indian–adjusted thresholds (because risk accrues earlier): treat at BMI ≥27.5 with comorbidity / ≥30 alone is too high a bar; Indian guidance favours lower action points and emphasises waist circumference (≥90 cm men, ≥80 cm women) and the waist-to-height ratio (ESI 2025 [ESI]).
- The BMI cut-points that trigger anti-obesity drug therapy (above) derive from the FDA labels and Indian guidelines; the corresponding BMI value used as a diabetes-screening trigger is lower (BMI >25, or >23 in persons of Asian descent) (FDA labels [FDA]; ESI 2025 [ESI]; G&G 14e Ch.51, p.1028).
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Obesity Pharmacotherapy
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