Obesity & Weight Loss
Obesity (BMI ≥30) affects over 42% of US adults and is associated with T2D, cardiovascular disease, and multiple cancers. The peptide-based GLP-1/GIP drug class has fundamentally changed the treatment landscape since 2021, with multiple FDA-approved agents achieving 15–22%+ weight loss in clinical trials.
Relevant Peptides
FDA-approved Wegovy: ~15% weight loss. The current clinical standard.
FDA-approved Zepbound: ~21% weight loss. Current efficacy benchmark.
Phase III: triple agonist with ~24% Phase II weight loss.
Phase III: 22.7% weight loss in CagriSema combination.
FDA-approved Saxenda: ~6% weight loss. First-generation.
FDA-approved Bydureon: ~3-4% weight loss.
Phase III failed primary endpoints; limited human efficacy.
FDA-approved for visceral fat in HIV lipodystrophy.
Regulatory Context
The GLP-1/GIP drug class is the most rapidly expanding area in obesity pharmacology:
- 2021: Semaglutide (Wegovy) approved for obesity
- 2022: Tirzepatide (Mounjaro) approved for T2D
- 2023: Tirzepatide (Zepbound) approved for obesity
- 2024-2025: Retatrutide, CagriSema, Orforglipron in Phase III
Compounding Status
Following FDA shortage resolution for both semaglutide (2024) and tirzepatide (2024), compounding these agents is now federally prohibited. Multiple enforcement actions have been taken against compound pharmacies.
Evidence Hierarchy
For obesity treatment, the evidence hierarchy is clear:
- Tirzepatide: 21% weight loss, Phase III RCT, FDA approved
- Semaglutide: 15% weight loss, Phase III RCT, FDA approved
- Liraglutide: 6% weight loss, Phase III RCT, FDA approved
- Exenatide: 3-4% weight loss, Phase III RCT, FDA approved
- AOD-9604: Failed Phase III
Prescribers and patients should start at the top of this hierarchy with evidence-based FDA-approved agents.
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