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🔹 FDA-approved agents (liraglutide, semaglutide, tirzepatide) now deliver 15–25% sustained weight loss 🔹 Next-gen triple agonists (e.g., retatrutide) in trials show even greater promise 🔹 Benefits extend beyond weight: T2D, CVD, MASLD, HFpEF, CKD, OSA Key clinical principles emerging: ✔️ Right patient, right molecule (BMI ≥30 or ≥27 with comorbidities) ✔️ Slow titration, lowest effective dose to reduce GI intolerance and lean mass loss ✔️ Clear targets: 5–10% loss in 3–6 months (15–20% in high-risk patients) ✔️ Structured switching from GLP-1 → dual/triple agonists when response plateaus ✔️ Ongoing monitoring (labs, BP, QoL, DEXA where indicated) ✔️ Strong patient counseling: lifelong therapy mindset, nutrition, resistance training In elderly patients, caution is key protecting muscle mass with adequate protein and strength training is non-negotiable
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