Tirzepatide vs Semaglutide: Zepbound vs Wegovy, Explained

“Tirzepatide vs semaglutide,” “Zepbound vs Wegovy” and “Mounjaro vs Ozempic” are among the most searched questions in metabolic medicine. This guide describes what the two molecules are, what direct comparisons exist, what each has shown in cardiovascular outcome trials, and how their US labels differ. It is descriptive only: it does not recommend either drug.

Updated November 4, 2026.

Which brand is which?

Tirzepatide is made by Eli Lilly and sold as Mounjaro (type 2 diabetes) and Zepbound (weight management and sleep apnea). Semaglutide is made by Novo Nordisk and sold as Ozempic (type 2 diabetes), Wegovy (weight management and related uses) and Rybelsus, an oral diabetes tablet. Each pair is the same molecule under two brand names, with different labeled uses. For deeper profiles, see our tirzepatide landscape and semaglutide landscape.

How do the mechanisms differ?

Semaglutide is a GLP-1 receptor agonist: it mimics one gut hormone. Tirzepatide is a dual agonist that activates both the GIP and GLP-1 receptors, as described in the published trial abstracts. Both are given as once-weekly injections in the trials discussed here, and the Zepbound label carries a boxed warning about thyroid C-cell tumors seen in rats. Whether the second receptor explains differences in trial results is a research question; the trials below measure outcomes, not mechanism.

What does head-to-head evidence show?

Two randomized trials compare the drugs directly, and both were funded by Eli Lilly and were open-label (participants and investigators knew which drug was used).

• SURMOUNT-5 (obesity, no diabetes): 751 adults were randomized to the maximum tolerated dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks. Mean weight change was -20.2% with tirzepatide and -13.7% with semaglutide; waist circumference fell 18.4 cm versus 13.0 cm. The results were published in the New England Journal of Medicine in 2025. A journal summary by the American College of Cardiology reported that discontinuation because of gastrointestinal events was 2.7% with tirzepatide and 5.6% with semaglutide.
• SURPASS-2 (type 2 diabetes): 1,879 patients were randomized to tirzepatide 5, 10 or 15 mg or semaglutide 1 mg for 40 weeks. HbA1c fell by 2.01, 2.24 and 2.30 percentage points on tirzepatide versus 1.86 on semaglutide, and weight differences versus semaglutide were -1.9, -3.6 and -5.5 kg. Nausea occurred in 17 to 22% of tirzepatide patients and 18% of semaglutide patients.

Both trials measured weight or blood sugar, not heart attacks or strokes. Both were sponsored by the maker of tirzepatide; we did not find an independent head-to-head trial.

What do the cardiovascular outcome trials show?

There is no trial that compares the two drugs on cardiovascular events. Each was tested in a different setting:

• SELECT (semaglutide 2.4 mg): 17,604 adults aged 45 or older with established cardiovascular disease and a BMI of 27 or more, without diabetes, were randomized against placebo. The primary composite (cardiovascular death, nonfatal heart attack or nonfatal stroke) occurred in 6.5% on semaglutide and 8.0% on placebo (hazard ratio 0.80, 95% CI 0.72 to 0.90). Adverse events led to permanent discontinuation in 16.6% versus 8.2%. Novo Nordisk funded the trial.
• SURPASS-CVOT (tirzepatide): 13,299 patients with type 2 diabetes and atherosclerotic cardiovascular disease were randomized to tirzepatide or dulaglutide, an active comparator rather than placebo. The primary event occurred in 12.2% versus 13.1% (hazard ratio 0.92, 95.3% CI 0.83 to 1.01). Tirzepatide met non-inferiority; superiority was not shown. Eli Lilly funded the trial.

These numbers should not be set side by side as if they came from one study. SELECT used a placebo comparator in people without diabetes; SURPASS-CVOT used an active comparator in people with diabetes. A hazard ratio against placebo and one against an active drug answer different questions.

How do the US labels differ?

As of November 4, 2026, per the labels on DailyMed:

• Wegovy (injection): reduce major adverse cardiovascular events in adults with established cardiovascular disease and obesity or overweight; weight reduction in adults and in patients aged 12 and older with obesity; and, under accelerated approval, noncirrhotic MASH with moderate to advanced fibrosis. A Wegovy tablet carries the cardiovascular and adult weight indications.
• Zepbound: weight reduction in adults with obesity, or overweight with a weight-related condition, and moderate to severe obstructive sleep apnea in adults with obesity. We did not find a cardiovascular indication on this label.
• Ozempic (injection): glycemic control in adults with type 2 diabetes, reduction of major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease, and reduction of kidney outcomes in adults with type 2 diabetes and chronic kidney disease.
• Mounjaro: glycemic control in adults and patients aged 10 and older with type 2 diabetes, and, since August 2026, reduction of major cardiovascular events in adults with type 2 diabetes at high risk.

Why are cross-trial comparisons risky?

Different trials enroll different people, use different doses and durations, and define endpoints differently. SELECT enrolled people with existing cardiovascular disease; SURMOUNT-5 enrolled adults with obesity without diabetes; SURPASS-2 enrolled people with type 2 diabetes. Placebo-controlled and active-comparator designs are not interchangeable, and open-label designs can influence how participants and investigators behave. Only SURMOUNT-5 and SURPASS-2 randomized the two drugs against each other, and only for weight and blood sugar. For help with reading trial records, see our ClinicalTrials.gov guide.

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This article is for informational and competitive-intelligence purposes only and is not medical advice. Approvals, labels and trial results change; verify details against current prescribing information and primary sources.