Tirzepatide (Zepbound)

Tirzepatide, marketed as Zepbound for obesity and Mounjaro for type 2 diabetes, is a first-in-class dual agonist that simultaneously activates both GLP-1 and GIP receptors. This dual mechanism amplifies satiety signaling beyond what GLP-1 alone can achieve, leading to calorie reduction that outpaces any single-receptor agent by over 32%, as shown by the 20.2% weight loss in SURMOUNT-5 versus Semaglutide 2.4mg (Wegovy)'s 13.7% — a 6.5 percentage point gap that is clinically enormous. FDA approved for chronic weight management in November 2023, landmark data from the SURMOUNT-1 trial at 15mg showed a mean 20.9% weight loss versus placebo's 3.1% over 72 weeks. A network meta-analysis gave tirzepatide the highest SUCRA score of 91.2 among GLP-1 class drugs. Dosing starts at 2.5mg weekly, titrating over 20 weeks to 10mg or 15mg via auto-injector with no food restrictions. Through Lilly Direct, self-pay price runs $299 to $449 monthly, down from $1,023 to $1,349 list. 2026 formulary changes dropped Zepbound from CVS Caremark, but Medicare's Bridge program from July 1, 2026 reopens coverage at ~$50 monthly for 3.4 million beneficiaries. Ideal for patients with BMI ≥30, or ≥27 with comorbidity, prioritizing maximum efficacy.