Wegovy vs Zepbound
The Most Important Obesity Drug Comparison — Direct Trial Data from SURMOUNT-5
Wegovy (semaglutide 2.4 mg) and Zepbound (tirzepatide 15 mg) are the two leading FDA-approved obesity drugs. SURMOUNT-5 (2025) directly compared them head-to-head: tirzepatide produced approximately 47% more relative weight loss. Yet Wegovy holds stronger cardiovascular outcome data (SELECT, 2023) while Zepbound's MMO trial is ongoing. Track either in Shotlee to measure your personal results.
Mechanism of Action
Wegovy (Semaglutide 2.4 mg)
- →GLP-1 receptor agonist — single incretin mechanism
- →Mimics endogenous GLP-1 released after meals
- →Suppresses appetite via hypothalamic GLP-1 receptors
- →Slows gastric emptying, prolonging satiety
- →Glucose-dependent insulin secretion enhancement
- →Half-life ~7 days; once-weekly autoinjector pen
- →SELECT trial: 20% MACE reduction in obesity + CVD (2023)
Zepbound (Tirzepatide 15 mg)
- →Dual GIP + GLP-1 receptor agonist
- →GIP receptor activation enhances adipose insulin sensitivity
- →GIP co-signalling may reduce GLP-1-driven nausea
- →Additive appetite suppression from two incretin pathways
- →Deeper weight loss vs GLP-1 monotherapy in all trials
- →Half-life ~5 days; once-weekly autoinjector pen
- →SURMOUNT-MMO cardiovascular outcomes trial ongoing
Head-to-Head Comparison
| Factor | Wegovy | Zepbound |
|---|---|---|
| Active molecule | Semaglutide | Tirzepatide |
| Receptor targets | GLP-1 only | GIP + GLP-1 |
| FDA approval (obesity) | June 2021 | November 2023 |
| Max dose | 2.4 mg weekly | 15 mg weekly |
| Weight loss — STEP-1/SURMOUNT-1 | 14.9% (sema 2.4 mg, 68 wks) | 20.9% (tirz 15 mg, 72 wks) |
| Direct head-to-head (SURMOUNT-5) | Reference arm | ~47% more weight loss vs Wegovy |
| Nausea incidence | ~44% (STEP-1) | ~31% (SURMOUNT-1 15 mg) |
| Cardiovascular outcome trial | SELECT 2023: 20% MACE reduction | MMO trial ongoing |
| Monthly cost (uninsured) | ~$1,300–1,400 | ~$1,000–1,200 |
| T2D brand | Ozempic | Mounjaro |
Data from STEP-1 (Wilding et al., NEJM 2021), SURMOUNT-1 (Jastreboff et al., NEJM 2022), and SURMOUNT-5 (2025). [1, 2, 3]
Weight Loss: The Numbers
Wegovy 2.4 mg (STEP-1)
14.9%
Mean body weight loss at 68 weeks in STEP-1 (N=1961, adults with obesity, no T2D).
Zepbound 15 mg (SURMOUNT-1)
20.9%
Mean body weight loss at 72 weeks in SURMOUNT-1 (N=2539, adults with obesity, no T2D).
SURMOUNT-5 head-to-head
~47%
More relative weight loss with tirzepatide vs semaglutide in the 2025 direct head-to-head trial.
Choose Based on Your Goal
Maximum weight loss
Strongest cardiovascular evidence
Lower nausea rates
Cost and insurance access
Earlier FDA approval history
Which Is Right for You?
For pure weight loss efficacy, the evidence favours Zepbound. SURMOUNT-5 (2025) is the definitive direct comparison: tirzepatide produced approximately 47% more relative weight loss than semaglutide. This is consistent with the individual trial data — SURMOUNT-1 showing 20.9% vs STEP-1's 14.9%.
Wegovy's key advantage is cardiovascular outcome data. The SELECT trial (2023) was the first obesity drug to show a statistically significant reduction in MACE (20%) in adults with obesity and established CVD — a landmark result. Zepbound's SURMOUNT-MMO cardiovascular trial is ongoing.
Tolerability: SURMOUNT-1 reported ~31% nausea rate vs ~44% for STEP-1. However, both trials used different populations and titration schedules, so direct nausea comparison should be interpreted with caution. Both drugs share the same class of GI side effects and are managed with slow dose escalation.
Track Either in Shotlee
Shotlee tracks Wegovy and Zepbound dose schedules, injection logs, weight charts, and side effect notes. If you switch between them, your baseline data stays intact for your prescriber to review.
Wegovy vs Zepbound: Common Questions
Zepbound. In individual trials: Zepbound 15 mg achieved ~20.9% weight loss (SURMOUNT-1) vs ~14.9% for Wegovy (STEP-1). In the 2025 SURMOUNT-5 direct head-to-head, tirzepatide produced approximately 47% more relative weight loss than semaglutide.
Currently, yes. SELECT (2023) showed a 20% MACE reduction with semaglutide 2.4 mg in people with obesity and CVD — the first obesity drug to achieve this. Zepbound's cardiovascular outcomes trial (SURMOUNT-MMO) is ongoing.
Trial data suggests Zepbound has lower nausea rates (~31% in SURMOUNT-1 vs ~44% in STEP-1 for Wegovy). Both drugs are managed with slow dose escalation to minimise GI side effects.
Yes, with prescriber guidance. No washout period is required. Start tirzepatide at 2.5 mg regardless of prior semaglutide dose and escalate normally. Track both in Shotlee so your prescriber can compare your response to each.
Both have limited obesity drug coverage. Some commercial plans, Medicare, and state Medicaid programmes cover one or both. Zepbound is often slightly less expensive without insurance. Check your specific plan formulary and manufacturer savings programmes.
References
- [1]Clinical TrialWilding JPH, et al. "Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP-1)." NEJM. 2021;384(11):989-1002.
- [2]Clinical TrialJastreboff AM, et al. "Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)." NEJM. 2022;387(3):205-216.
- [3]Clinical TrialLincoff AM, et al. "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)." NEJM. 2023;389(24):2221-2232.
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