Zepbound vs Wegovy: the head-to-head trial, the labels and the price

Most GLP-1 comparisons stitch together separate placebo-controlled trials, which enrolled different people under different conditions. Zepbound against Wegovy is the exception. SURMOUNT-5, published in The New England Journal of Medicine in July 2025 (Aronne and colleagues), was "a phase 3b, open-label, controlled trial" in which "adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks." A total of 751 people were randomized.

The result, in the paper's words: "The least-squares mean percent change in weight at week 72 was -20.2% (95% confidence interval [CI], -21.4 to -19.1) with tirzepatide and -13.7% (95% CI, -14.9 to -12.6) with semaglutide (P<0.001)." Waist circumference fell "-18.4 cm ... with tirzepatide and -13.0 cm ... with semaglutide". "Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%." On side effects the abstract says only that "the most common adverse events in both treatment groups were gastrointestinal, and most were mild to moderate in severity and occurred primarily during dose escalation."

The labels give each drug's own placebo-controlled result in adults with obesity or overweight and without diabetes. Zepbound's Study 1 ran 72 weeks in 2,539 adults at fixed doses; Wegovy's Study 2 ran 68 weeks in 1,961 adults at 2.4 mg. Both groups started near 105 kg with a BMI around 38. The figures below are for everyone randomized, and each drug is compared only with its own placebo group.

Wegovy also comes as a 7.2 mg weekly pen, Wegovy HD, tested in its own 72-week trials, and as a 25 mg daily tablet; our comparison of every approved GLP-1 carries those figures, and the pill against the pen has its own guide. Neither the 7.2 mg dose nor the tablet was in SURMOUNT-5.

Semaglutide, the drug in Wegovy and Ozempic, is a GLP-1 receptor agonist: it activates the receptor for GLP-1, a gut hormone the label calls "a physiological regulator of appetite and caloric intake". Tirzepatide, the drug in Zepbound and Mounjaro, is what its label calls "a GIP receptor and GLP-1 receptor agonist", acting on a second gut-hormone receptor as well. Both labels say the drug delays gastric emptying. Both are injected once a week, "at any time of day, with or without meals", into the abdomen or thigh; Wegovy's label adds the upper arm, and Zepbound's adds the back of the upper arm when another person gives the injection.

Both labels step the dose up every four weeks to limit stomach side effects. Zepbound starts at 2.5 mg, which "is for treatment initiation and is not approved as a maintenance dosage", moves to 5 mg after four weeks, and "may be increased in 2.5 mg increments, after at least 4 weeks on the current dose" to a maintenance dose of 5, 10 or 15 mg chosen on "treatment response and tolerability". Wegovy starts at 0.25 mg and steps through 0.5, 1 and 1.7 mg to 2.4 mg, the recommended maintenance dose (1.7 mg is the alternative, and 7.2 mg is allowed after at least four weeks at 2.4 mg when more weight loss is clinically indicated). Zepbound comes as single-dose pens, single-dose vials, four-dose vials and a four-dose KwikPen; Wegovy as single-dose pens, a four-dose FlexTouch pen, syringes and tablets. The vial and KwikPen matter for price, below.

The two labels share their core warnings: the boxed warning on thyroid C-cell tumors seen in rodents, acute pancreatitis, gallbladder disease, acute kidney injury from fluid loss, severe gastrointestinal reactions, hypersensitivity, low blood sugar when combined with insulin or a sulfonylurea, diabetic retinopathy complications in type 2 diabetes, and pulmonary aspiration (inhaling stomach contents) under general anesthesia or deep sedation. Wegovy's label also lists a heart rate increase as a warning; Zepbound's reports a mean rise of 1 to 3 beats per minute among its adverse reactions. Nausea led both drugs' adverse-reaction tables: 25 to 29 percent on Zepbound against 8 on placebo by dose, and 44 percent on Wegovy against 16. Injection-site reactions were reported by 6 to 8 percent on Zepbound against 2, and 1.4 percent on Wegovy against 1.

Those two rows are not a verdict on which drug is gentler. Each label opens its adverse-reactions section by saying that rates from one drug's trials "cannot be directly compared" to another's, because the trials enrolled different people and counted differently, and the head-to-head trial's abstract reports only that gastrointestinal events were the most common in both arms. Our side-effects guide prints each label's full table with its own placebo column, the serious-risk rates, and the stop-and-call symptoms; hair loss, reported at 3 percent on Wegovy and 4 to 5 percent on Zepbound against 1 on placebo, has its own page.

Both makers publish cash prices. Lilly's Zepbound page, read September 24, 2026, lists the KwikPen or four single-dose vials "Self-pay, starting at $299" a month, and says "The $299 per month is for the Zepbound KwikPen or vial, not Zepbound single-dose Pen." Its offer terms give the regular KwikPen price by dose: "$299 for 2.5 mg, $399 for 5 mg, $499 for 7.5 mg, $699 for 10 mg, $699 for 12.5 mg, and $699 for 15 mg." A $449 purchase offer applies automatically to the first KwikPen fill of 7.5 mg and up and continues only if each refill is bought "within 45 days of the delivery/received date" of the previous one; after that the terms say the "purchase offer will not apply", and Lilly may end the offer "at any time". Novo's NovoCare Pharmacy page, read the same day, prices the Wegovy pen at "$199 for each month of 0.25 mg and 0.5 mg" for two monthly fills for new patients through December 31, 2026, "then $349 per month for Wegovy® 0.25 mg, 0.5 mg, 1 mg, 1.7 mg or 2.4 mg and $399 per month for Wegovy® HD (semaglutide) injection 7.2 mg", a month being one box of four pens.

So at a maintenance dose a cash payer spends $349 a month on Wegovy through 2.4 mg ($399 at 7.2 mg), and on the Zepbound KwikPen $399 at 5 mg, or $449 at 10 or 15 mg with on-time refills and $699 without (our arithmetic from the two grids above). With commercial insurance that covers the drug, both savings cards bring the cost to as little as $25, with savings capped at $100 a month, and Medicare's GLP-1 Bridge covers both for eligible Part D enrollees at a $50 monthly copay, Zepbound as the KwikPen only. Our Wegovy and Zepbound cost guide carries the full grids and conditions, and the GLP-1 program directory lists which online programs prescribe each drug and what they add to the maker's price.

On weight alone, the randomized head-to-head favors Zepbound by 6.5 percentage points of body weight at 72 weeks (20.2 against 13.7), in people without type 2 diabetes, at the highest dose each person could tolerate. On cash price at maintenance, Wegovy through 2.4 mg costs $50 to $350 a month less than the Zepbound KwikPen, depending on dose and refill timing. On risk, the labels share their core warnings and offer no basis for calling one gentler. The other approved uses differ: Wegovy carries indications for cardiovascular risk reduction in adults with established heart disease and for MASH, a liver disease, and Zepbound one for obstructive sleep apnea in adults with obesity. A prescriber weighs those against the rest of a person's health.