PMID-40743997 — EASO Framework for Obesity Pharmacological Treatment

[DRAFT — authored 2026-04-18. Guideline reference.]

Citation

Busetto L, Dicker D, Frühbeck G, Halford JCG, Sbraccia P, Yumuk V, Abdel-Wahab YHA, Albrecht E, Baretic M, Batterham RL, Boyle J, Caballero B, Carlsson LMS, Davies MJ, Hauner H, Heymsfield SB, Hopkins M, Kwaan M, Laville M, Lecube A, Nair SK, Rössner S, Toplak H, van der Valk ESM, Vettor R, Woodward E, Yeo GSH, Yumuk VD. European Association for the Study of Obesity (EASO) Framework for the Pharmacological Treatment of Obesity in Adults: A Consensus Statement. Nat Med. 2025;31(8):2450-2462. doi: 10.1038/s41591-025-03814-2. PMID: 40743997.

Scope

European Association for the Study of Obesity (EASO) consensus framework guiding pharmacological treatment of obesity across the European clinical-care landscape, harmonizing prior national-society guidance with 2024-2025 evidence (SURMOUNT series, STEP extension, SELECT, SURPASS series, REDEFINE interim).

Key Framework Elements

Philosophy

Obesity treated as chronic relapsing disease requiring long-term pharmacotherapy.
Goal paradigm: health-outcome improvement (CV, renal, hepatic, quality-of-life), not solely weight percentage.
Weight-loss threshold for clinical benefit: ≥5% body weight; most modern GLP-1/GIP-GLP-1 agents exceed ≥10-20%.

Eligibility

BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidity.
Adolescent criteria explicitly endorsed per STEP TEENS and SURPASS-PEDS (12+ years).
Pregnancy: contraindicated; preconception counseling required.

First-line Agents

Semaglutide 2.4 mg weekly (Wegovy) — weight loss and CV benefit established.
Tirzepatide 5-15 mg weekly (Mounjaro/Zepbound) — largest monotherapy weight-loss effect.
Liraglutide 3.0 mg daily (Saxenda) — older agent, retained as option where weekly injection preference or access constraints.

Emerging Agents (Acknowledged but not first-line endorsed)

Retatrutide (triple GLP-1/GIP/glucagon): ~24% weight loss in Phase 2; Phase 3 (TRIUMPH) ongoing.
CagriSema (cagrilintide + semaglutide): REDEFINE-2 demonstrates superiority to semaglutide; REDEFINE-1 result more modest. Status pending EMA regulatory action.
Orforglipron (oral non-peptide GLP-1): ATTAIN-1 evidence supports pathway; not yet approved.

Principles of Use

Titration: Slow titration reduces GI intolerance; minimum 4-8 weeks per step.
Response evaluation: Assess weight loss and comorbidity endpoints at 3-6 months; if <5% loss at recommended dose, consider switch.
Duration: Indefinite in most patients; weight regain anticipated on cessation.
Combination therapy: Not routinely recommended; sequential trials preferred.
Adjunct to lifestyle: Pharmacotherapy is adjunct, not replacement, for nutrition/physical activity counseling.

Safety Monitoring Framework

Baseline: renal function, LFTs, HbA1c, lipid panel, mental-health screen.
Periodic: same; add ocular history/symptom screen (NAION awareness post-EMA classification).
GI tolerance: dose-adjust or switch for persistent severe symptoms.
Thyroid: no routine US imaging recommended; counsel on C-cell risk per label.
Gallbladder: monitor for symptomatic cholelithiasis; rapid weight loss is the principal risk.

Special Populations

Elderly: Lean-mass loss concern; prioritize resistance exercise and adequate protein.
T2D + CV disease: Semaglutide or tirzepatide per outcome trial evidence.
T2D + CKD: Semaglutide (FLOW).
HFpEF: Semaglutide or tirzepatide (STEP-HFpEF, SUMMIT).
MASH/MASLD: Tirzepatide or semaglutide.
Sleep apnea: Tirzepatide (SURMOUNT-OSA).

Divergence from US Guidelines

EMA NAION "very rare" classification (June 2025) incorporated; EASO explicitly advises patient counseling on ocular symptoms. US labels (as of framework publication) had not adopted this classification.
EASO explicitly addresses compounded-product harm; strongly advises against compounded semaglutide outside of documented patient-specific medical necessity per European national compounding laws.

Evidence Level

Level I — Consensus statement with systematic-review underpinning.

Limitations (Author-acknowledged)

Heterogeneity of national regulatory environments across EASO member countries.
Data on adolescent, pregnant, and advanced-age populations still limited.
Long-term (>5 year) outcome durability being accumulated.

Linked Peptides

Related References

Orchestrator Notes

EU-origin guideline balancing the US-heavy evidence base in Module 5.
Useful for presenting international perspective in Lesson 5.1 comparative framework discussion.
Co-authored by Davies MJ (first author of REDEFINE-2) and Frühbeck (key obesity guideline figure).
Author list abbreviated above to key contributors; verify full author list at time of formal review.

PMID-40743997 – EASO Framework Obesity Pharmacological Treatment