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et al., A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH, N Engl J Med

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Current FDA-Approved Weight Loss Medications: GLP-1 and Dual Agonists (Most Effective): Tirzepatide (Zepbound) Approval: November 2023 Mechanism: Dual GIP/GLP-1 receptor agonist Average Weight Loss: 15-22% of body weight Administration: Weekly injection Semaglutide (Wegovy) Approval: June 2021 Mechanism: GLP-1 receptor agonist Average Weight Loss: 10-15% of body weight Administration: Weekly injection Liraglutide (Saxenda) Approval: December 2014 Mechanism: GLP-1 receptor agonist Average Weight Loss: 5-8% of body weight Administration: Daily injection Older Weight Loss Medications (Less Effective): Phentermine-Topiramate (Qsymia) Approval: July 2012 Mechanism: Appetite suppressant + anticonvulsant Average Weight Loss: 7-9% of body weight Administration: Daily pill Naltrexone-Bupropion (Contrave) Approval: September 2014 Mechanism: Opioid antagonist + antidepressant Average Weight Loss: 4-5% of body weight Administration: Daily pill Orlistat (Xenical, Alli) Approval: April 1999 (prescription), 2007 (OTC) Mechanism: Lipase inhibitor (blocks fat absorption) Average Weight Loss: 3-5% of body weight Administration: Three times daily with meals Phentermine (Adipex-P, Lomaira) Approval: 1959 Mechanism: Appetite suppressant Average Weight Loss: 5-7% of body weight Administration: Daily pill Restriction: Short-term use only (12 weeks) Effectiveness Ranking: Why GLP-1 Medications Dominate: The top three most effective medications are all GLP-1 receptor agonists

Medication use: Certain medications, such as proton pump inhibitors (PPIs), can interfere with B12 absorption

Weight loss plateau mechanisms appear to be primarily metabolic adaptation rather than receptor tolerance