Wegovy HD vs. Zepbound: semaglutide 7.2 mg against tirzepatide

Wegovy HD is not a new molecule. It is the same semaglutide as standard Wegovy, delivered at three times the old 2.4 mg ceiling from a single-dose 7.2 mg/0.75 mL pen, and it acts on one receptor, GLP-1. Zepbound is tirzepatide, which activates both the GIP and GLP-1 receptors. The road to each top dose is different. Wegovy climbs through 0.25, 0.5, 1, 1.7 and 2.4 mg at four-week steps, and the label permits 7.2 mg only after at least four weeks on 2.4 mg when further weight reduction is clinically indicated, so the first 7.2 mg dose comes no earlier than week 21. Zepbound starts at 2.5 mg and rises by 2.5 mg no sooner than every four weeks to a 15 mg maximum. The labels diverge beyond weight: Wegovy injection also carries cardiovascular risk reduction and MASH indications, while Zepbound carries obstructive sleep apnea. The 7.2 mg dose itself is approved for adult weight reduction only.

No trial has put Wegovy HD against Zepbound, so the fair comparison is two labels read side by side. In the Wegovy label's Study 8 (STEP UP), 1,407 adults with obesity and without diabetes were randomized 5:1:1 to semaglutide 7.2 mg, 2.4 mg or placebo for 72 weeks. Intention-to-treat weight change was -18.8% on 7.2 mg, -15.5% on 2.4 mg and -3.9% on placebo, and 45.5% of the 7.2 mg group lost at least a fifth of their body weight, against 32.3% on 2.4 mg. In adults with type 2 diabetes (Study 9, STEP UP T2D) the same three arms reached -13.2%, -10.4% and -3.8%. Zepbound's label reports SURMOUNT-1: over 72 weeks, tirzepatide produced -15.0% at 5 mg, -19.5% at 10 mg and -20.9% at 15 mg, against -3.1% on placebo. The only randomized trial involving both molecules is SURMOUNT-5 (New England Journal of Medicine, 2025), where tirzepatide reduced weight by 20.2% against 13.7% for semaglutide, but semaglutide there was capped at 2.4 mg. On paper the gap has narrowed to about two percentage points; whether it has closed is a question no trial has yet been designed to answer.

Both drugs are dominated by gastrointestinal effects that cluster around dose increases. In the Wegovy label's pooled 7.2 mg trials, nausea affected 39% on 7.2 mg against 35% on 2.4 mg and 13% on placebo, vomiting 22% against 16% and 6%, and constipation 20% against 19% and 8%. The new signal is dysesthesia, meaning tingling, burning or painful skin, reported by 22% on 7.2 mg, 6% on 2.4 mg and 0.3% on placebo; 23% of those affected had their dose reduced. Hair loss reached 6%. Zepbound's label lists nausea in 25-29% of patients across doses, diarrhea in 19-23%, vomiting in 8-13% and injection-site reactions in 6-8%, with dysesthesia at 0.4% or less. Both carry the boxed warning for thyroid C-cell tumors, both are contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2, and both list pancreatitis, gallbladder disease and aspiration under anesthesia.

Wegovy HD is built for a narrow group: people already on Wegovy 2.4 mg, tolerating it, and still short of the goal their prescriber set. For them, stepping up keeps the same molecule, the same weekly day and the cardiovascular indication, and avoids restarting a fresh titration at 2.5 mg. It fits less well for anyone who struggled with nausea at 2.4 mg, and the 22% dysesthesia rate deserves a conversation before the step. Zepbound suits someone starting from scratch who wants the drug with the larger reported weight reduction at its top dose, and it is the only one of the pair labeled for obstructive sleep apnea. Price may tip it: NovoCare lists Wegovy HD at $399 a month self-pay (NovoCare Wegovy price guide, April 2026 edition, checked 28 Sep 2026), while LillyDirect lists Zepbound at $449 a month from 7.5 mg upward (usetemi.com/medications/zepbound, checked 28 Sep 2026). Neither suits someone with a personal or family history of medullary thyroid carcinoma or MEN 2. Neither fixes a routine problem either: if weekly doses are being missed, a higher ceiling changes little. Make the decision with a prescriber who knows your full history.