Tirzepatide vs Semaglutide

SURMOUNT-5 head-to-head: −20.2% with tirzepatide vs −13.7% with semaglutide at 72 weeks; more patients reached ≥15–25% loss. Network/meta-analyses echo greater loss with tirzepatide. ^{[1][2][3][20][24]}

SURPASS-2: tirzepatide 5–15 mg reduced A1C and weight more than semaglutide 1 mg over 40 weeks; multiple NMAs show larger A1C drops with tirzepatide. ^[4][21][25]

SELECT: semaglutide 2.4 mg reduced MACE by 20% vs placebo in obesity without diabetes. Tirzepatide's SURPASS-CVOT showed non-inferiority vs dulaglutide (not superiority vs placebo); HFpEF data are promising but not a broad CVOT win yet. ^{[6][7][8][18][19]}

Real-world and trial curves show larger early weight and A1C deltas with tirzepatide during escalation; SURMOUNT-5 and comparative analyses show higher odds of ≥10–15% loss earlier. ^[1][24]

GI AEs common for both during titration. Some meta-analyses suggest higher overall GI AE rates with higher-dose tirzepatide; semaglutide shows more gallbladder events in some analyses. Discontinuations in SURMOUNT-5 were numerically higher with semaglutide. ^[1][22][23]

Semaglutide offers an oral option (Rybelsus) though with strict fasting and ~0.8% bioavailability; both have weekly injections. Tirzepatide has no oral form. ^[10][11][12]

List prices are high for both; manufacturers offer direct self-pay vial programs around $499/month (Zepbound) and similar cash offers for Wegovy via NovoCare. Coverage varies by plan/formulary. ^[14][15][16]

Both are FDA-approved biologic peptide drugs with fixed-dose pens/vials and rigorous QC; avoid compounded or "research" semaglutide/tirzepatide due to FDA warnings. ^[9]