Tirzepatide (Zepbound / Mounjaro)

Tirzepatide, marketed as Zepbound for weight management and Mounjaro for type 2 diabetes, is a once-weekly subcutaneous injection that simultaneously activates two incretin hormone receptors: GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). This dual mechanism produces greater reductions in caloric intake, enhanced energy metabolism, and superior glycemic control compared to GLP-1 agonism alone. In the SURMOUNT-1 trial (N=2,539, 72 weeks), patients on the highest 15 mg dose lost an average of 22.5% of their body weight, with 50-57% achieving 20% or more weight loss. The landmark SURMOUNT-5 head-to-head trial (N=751, 72 weeks) showed tirzepatide users lost 20.2% vs 13.7% for semaglutide -- a 47% greater relative reduction. Critically, 19.7% of tirzepatide patients lost 30% or more body weight, versus just 6.9% of semaglutide patients. GI discontinuation was lower with tirzepatide (2.7%) than semaglutide (5.6%). Side effects include nausea, diarrhea, vomiting, constipation, and abdominal pain. Black box warning for thyroid C-cell tumors (based on rodent studies) contraindicates use in patients with personal or family history of medullary thyroid carcinoma or MEN2 syndrome. Cost: List price $1,000-$1,086/month. Lilly self-pay vial program $399-$549/month. Savings card as low as $25/month for commercially insured. Medicare Part D covers Zepbound at $50/month via GLP-1 Bridge Program from July 2026. Eligibility: adults with BMI 30+ or BMI 27+ with a weight-related comorbidity.