Wegovy vs Zepbound: Side-Effect Rates From the Two FDA Labels

The difference is the molecule and the approved uses. Wegovy's semaglutide is a GLP-1 analogue with 94% of the sequence of human GLP-1, per the 2024 FDA label.1 Zepbound's tirzepatide is a dual GIP and GLP-1 receptor agonist, per the August 2026 label.2 Both are approved for weight management in adults with a BMI of 30 or more, or 27 or more with a weight-related condition.4 Wegovy is also approved from age 12, to cut heart risk and for the liver disease MASH; Zepbound is also approved for sleep apnea.1,5,2

The table draws on the Wegovy labels of 2024 and June 2026 and the Zepbound label of August 2026.1,5,2

The Wegovy vs Zepbound compare page sets the active ingredient, the form, the approved uses and the pharmacy acquisition cost of each drug side by side. Readers whose prescriber has settled on semaglutide can start at semaglutide online.

On the FDA labels, Wegovy (semaglutide) reports higher rates of the common stomach side effects than Zepbound (tirzepatide), but each drug was tested against its own placebo group, not against the other. In the pooled STEP 1, 2 and 4 trials, nausea hit 44% of adults on Wegovy 2.4 mg versus 16% on placebo, per the June 2026 label.6 In the pooled SURMOUNT-1 and SURMOUNT-2 trials, nausea hit 25% to 29% on Zepbound 5 mg to 15 mg versus 8% on placebo, per the August 2026 label.2

The rates below come from the Wegovy label of June 2026 (pooled STEP 1, 2 and 4, 2.4 mg dose) and the Zepbound label of August 2026 (pooled SURMOUNT-1 and SURMOUNT-2, 5 mg, 10 mg and 15 mg doses), each next to its own placebo group.6,2

The share who stopped for side effects is close between the two drugs. On Wegovy, 6.8% stopped versus 3.2% on placebo, most often for nausea (1.8% versus 0.2%), vomiting (1.2% versus 0%) and diarrhea (0.7% versus 0.1%).6 On Zepbound, 4.8% to 6.7% stopped versus 3.4% on placebo.2 The placebo groups differ too: 16% of placebo patients in the STEP pool reported nausea, against 8% in the SURMOUNT pool, so the two label tables are not a like-for-like test.6,2

SURMOUNT-5, a trial that gave both drugs to similar people, reported that the most common adverse events in both the tirzepatide and the semaglutide groups were gastrointestinal, most were mild to moderate, and most occurred during dose escalation.3

Zepbound (tirzepatide) caused more weight loss than Wegovy (semaglutide) in a head-to-head trial. SURMOUNT-5, published in 2025, randomized 751 adults with obesity but no type 2 diabetes to the highest tolerated dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) weekly for 72 weeks.3 Tirzepatide was superior for body weight and waist circumference at week 72, and more people on tirzepatide lost at least 10%, 15%, 20% and 25%.3 The trial was open-label and funded by Eli Lilly, Zepbound's maker.3

Seven of the SURMOUNT-5 authors were Eli Lilly staff, and the trial is registered as NCT05822830.3

Each label also reports its own placebo-controlled trials. The numbers below count everyone who started the trial, from the Zepbound label of August 2026 (SURMOUNT-1, 72 weeks, adults with obesity and no diabetes) and the Wegovy label of June 2026 (STEP 1 at 68 weeks and STEP UP at 72 weeks, adults without diabetes).2,6

These trials differ in length, in placebo response and in who joined, so each label number stands against its own placebo, not against the other drug. Counting everyone who started, Zepbound 15 mg beat placebo by 17.8 percentage points at week 72 (95% CI -19.3 to -16.3),2 and Wegovy 2.4 mg beat placebo by 12.4 points at week 68 in STEP 1 (95% CI -13.3 to -11.6).6 In STEP UP, the 7.2 mg dose of Wegovy beat the 2.4 mg dose by 3.3 points (95% CI -4.9 to -1.6).6

This article is for information only and is not medical advice. Talk to a licensed clinician before you start, change or stop a medicine.