Zepbound vs Wegovy: Weight Loss Results and How to Choose
Zepbound vs Wegovy: Weight Loss Results & How to Choose
Medical disclaimer: This article is for education only and is not medical advice. Medication choices, dosing, and side-effect management should be made with a licensed clinician using the FDA label and your personal medical history.
If you're comparing Zepbound vs Wegovy, you're usually trying to answer one question:
"Which one is likely to help me lose more weight—without wrecking my quality of life or my budget?"
The most direct head-to-head evidence to date suggests Zepbound (tirzepatide) produces greater average weight loss than Wegovy (semaglutide) at 72 weeks in adults with obesity but without diabetes: −20.2% vs −13.7% in a phase 3b randomized trial (NEJM, 2025).
But "better on average" isn't always "best for you." Below is a practical, evidence-backed comparison—mechanism, results, dosing, side effects, indications, and how to track fat vs muscle so your progress is real.
Quick takeaways (scan this first)
| Topic | Zepbound | Wegovy |
|---|---|---|
| What it is | Dual GIP/GLP-1 receptor agonist (Zepbound FDA label) | GLP-1 receptor agonist (Wegovy FDA label) |
| Available forms | Weekly injection | Weekly injection or daily pill (NPR) |
| Average weight loss in a head-to-head trial (72 weeks) | −20.2% | −13.7% (NEJM, 2025) |
| Standard titration (injection) | 2.5 mg → 5 → 7.5 → 10 → 12.5 → 15 mg (step up every ≥4 weeks) (Zepbound FDA label) | 0.25 mg → 0.5 → 1.0 → 1.7 → 2.4 mg (step up every 4 weeks) (Wegovy FDA label) |
| Common side effects | GI effects (nausea/diarrhea/vomiting/constipation) are common; boxed warning for thyroid C-cell tumors (rodents) (Zepbound FDA label) | Similar GI profile and boxed warning; also warns about gallbladder disease, pancreatitis, etc. (Wegovy FDA label) |
| Unique FDA-approved indications (besides weight management) | Moderate-to-severe obstructive sleep apnea in adults with obesity (Zepbound FDA label) | Reduced risk of major adverse cardiovascular events in certain adults with established CVD and obesity/overweight (Wegovy FDA label) |
Zepbound vs Wegovy: what are they (and why do they work)?
Both medications are used with a reduced-calorie diet and increased physical activity.
Wegovy (semaglutide): GLP-1 only
Semaglutide is a GLP-1 receptor agonist that supports weight loss through multiple pathways including improving glucose-dependent insulin secretion, slowing gastric emptying, and increasing satiety (so you feel full sooner and longer) (StatPearls: Semaglutide).
Wegovy is available as a once-weekly injection—and the FDA has now also approved a once-daily oral tablet (NPR; NBC News). The pill version offers a needle-free option for people who prefer not to inject. For a detailed breakdown of the oral option, see our guide: Wegovy pills: 2026 guide to approval, cost & results.
Zepbound (tirzepatide): GLP-1 + GIP
Tirzepatide activates two incretin receptors (GIP and GLP-1). Reviews of clinical trial data describe tirzepatide as a dual GIP/GLP-1 receptor co-agonist associated with meaningful body-weight reductions in clinical trials (PMC review). Zepbound is currently available as a once-weekly injection.
A simple way to picture it: Wegovy turns one appetite dial down; Zepbound turns two. The head-to-head trial suggests that can translate to greater average weight loss (NEJM, 2025).
Results: how much weight loss can you expect?
The most direct comparison: tirzepatide vs semaglutide at 72 weeks
In a randomized phase 3b trial in adults with obesity but without type 2 diabetes, tirzepatide produced a larger mean percent weight loss than semaglutide at week 72: −20.2% vs −13.7% and also reduced waist circumference more (−18.4 cm vs −13.0 cm) (NEJM, 2025).
What "on-label" trials show for each drug
| Trial snapshot | Outcome |
|---|---|
| Tirzepatide in adults with obesity (SURMOUNT-1) | Mean weight change at 72 weeks: −20.9% (15 mg) vs −3.1% placebo (NEJM, 2022) |
| Semaglutide in adults with obesity/overweight (STEP 1, injection) | Mean weight change at 68 weeks: −14.9% vs −2.4% placebo (NEJM, 2021) |
| Oral semaglutide 50 mg in adults with obesity/overweight | Mean weight change at 68 weeks: −15.1% vs −2.4% placebo (PubMed) |
A "trial-average math" shortcut (to estimate pounds)
Trial percentages can feel abstract. Converting them to pounds can make planning easier.
- Estimated Wegovy trial-average loss ≈ 0.149 × starting weight (NEJM, 2021)
- Estimated Zepbound trial-average loss (high dose) ≈ 0.209 × starting weight (NEJM, 2022)
Example: at 220 lb, that's ~33 lb (Wegovy trial-average) vs ~46 lb (Zepbound trial-average).
Dosing schedules (and why titration changes the timeline)
Both drugs are designed to ramp slowly to improve tolerability.
Zepbound dosing chart (typical escalation)
| Weeks | Dose |
|---|---|
| 1–4 | 2.5 mg weekly (initiation) |
| 5–8 | 5 mg weekly |
| 9–12 | 7.5 mg weekly (if needed) |
| 13–16 | 10 mg weekly (if needed) |
| 17–20 | 12.5 mg weekly (if needed) |
| 21+ | 15 mg weekly (if needed; max) |
Zepbound dosing increases are typically in 2.5 mg increments after at least 4 weeks on the current dose; maintenance doses include 5, 10, or 15 mg weekly for weight management (Zepbound FDA label).
Missed dose rule (Zepbound): take as soon as possible within 4 days; otherwise skip and resume your schedule (Zepbound FDA label).
Wegovy dosing chart (standard escalation—injection)
| Weeks | Dose |
|---|---|
| 1–4 | 0.25 mg weekly |
| 5–8 | 0.5 mg weekly |
| 9–12 | 1.0 mg weekly |
| 13–16 | 1.7 mg weekly |
| 17+ | 2.4 mg weekly (or 1.7 mg if not tolerated) |
Source: Wegovy FDA label. For a deeper walk-through, see our guide: Wegovy dosing chart and weekly schedule.
Wegovy pill dosing
The oral Wegovy tablet also uses a dose-escalation (titration) approach—starting low and increasing—because gastrointestinal side effects are common early and during dose jumps (NBC News). The pill is taken once daily (vs. once weekly for the injection) and must be taken on an empty stomach with a sip of water, then you wait 30 minutes before eating, drinking, or taking other oral medications (NPR; USA Today). For complete pill dosing details, see: Wegovy pills: 2026 guide to approval, cost & results.
Side effects and safety: what's similar, what's different?
What's similar
Both medications:
- Commonly cause GI side effects, especially during dose escalation.
- Carry a boxed warning about thyroid C-cell tumors observed in rodents, and are contraindicated with a personal/family history of medullary thyroid carcinoma (MTC) or MEN2 (Zepbound FDA label; Wegovy FDA label).
- Warn about serious but uncommon risks including pancreatitis and gallbladder disease, and both delay gastric emptying (relevant for anesthesia/deep sedation) (Zepbound FDA label; Wegovy FDA label).
The Wegovy pill shares a similar GI side-effect profile with the injection—nausea, diarrhea, and vomiting are commonly reported (NPR).
Notable differences to discuss with your clinician
- Oral contraceptives: Zepbound can affect absorption of oral medications due to delayed gastric emptying; the label specifically advises switching to a non-oral contraceptive or adding a barrier method for 4 weeks after initiation and each dose escalation if using oral contraceptives (Zepbound FDA label).
- Indication differences: Wegovy includes an indication to reduce major adverse cardiovascular events in certain adults with established CVD and obesity/overweight (Wegovy FDA label). Zepbound includes treatment of moderate-to-severe obstructive sleep apnea in adults with obesity (Zepbound FDA label).
Fat loss vs muscle loss: the detail most "Zepbound vs Wegovy" articles miss
Scale weight can drop for multiple reasons: fat, muscle, glycogen, and water. That's why the scale can be a frustrating scoreboard—especially if you're lifting weights, changing carbs/sodium, or dealing with GI side effects.
Wegovy body composition data (DEXA substudy)
In an exploratory DEXA analysis from STEP 1, semaglutide was associated with reductions in total fat mass and visceral fat mass, while lean mass also decreased in absolute terms (though lean mass percentage improved due to significant fat loss) (Journal of the Endocrine Society, 2021).
Zepbound: why body composition tracking matters even more when weight loss is larger
Tirzepatide can produce very large total weight loss in trials (e.g., roughly −20.9% at 72 weeks on 15 mg in SURMOUNT-1) (NEJM, 2022). When total weight loss is that big, it's common for some of the loss to be lean mass in absolute terms—even if the majority is fat.
That's why a "bigger weight-loss drug" can increase the importance of tracking body composition: you want to verify that you're losing mostly fat, and catch early signs of excessive lean-mass loss so you can adjust protein intake, resistance training, and the pace of loss.
The BodySpec approach: track what the scale can't show
A bathroom scale tells you only total weight change—not whether you're losing fat, holding onto muscle, or just bouncing water weight.
A DEXA scan can quantify:
- fat mass vs lean mass (so you can see if your plan is "muscle-sparing")
- regional fat distribution
- an estimate of visceral fat (deep belly fat)
Start here if you're new: The DEXA scan: body fat, muscle, and bone density testing.
A simple tracking cadence: baseline → 8–12 weeks → maintenance dose → every 3–6 months.
Prep matters for trend accuracy: Prepare for your BodySpec scan.
How to choose: a decision checklist to bring to your appointment
1) How important is "maximum average weight loss" vs "best-fit indication"?
- If the goal is maximum average weight loss, the head-to-head data favors tirzepatide (NEJM, 2025).
- If you specifically need Wegovy's CV risk-reduction indication (for qualifying adults), that may weigh heavily (Wegovy FDA label).
- If obstructive sleep apnea is part of the picture, Zepbound has an OSA indication in adults with obesity (Zepbound FDA label).
2) Injection vs. pill: what fits your routine?
If needles are a barrier, Wegovy now offers a daily pill option. The trade-off: the pill requires strict timing rules (empty stomach, wait 30 minutes before eating/drinking) every day, while the injection is just once weekly (NPR). In clinical trials, people who didn't follow the strict pill schedule lost less weight (NBC News).
| Feature | Zepbound | Wegovy injection | Wegovy pill |
|---|---|---|---|
| How often | Weekly | Weekly | Daily |
| Timing rules | No "empty stomach" rule | No "empty stomach" rule | Empty stomach + wait 30 min |
| Needles | Yes | Yes | No |
3) Which side effects are most likely to derail you?
Because both commonly cause GI symptoms, the practical question is often tolerability over time, especially during titration. In the head-to-head trial, GI adverse events were common in both groups and were generally mild to moderate during dose escalation (NEJM, 2025).
4) How likely are you to get insurance coverage?
Coverage varies widely by plan type.
- Medicaid obesity-drug coverage is limited; as of August 2024, 13 states covered GLP-1s for obesity treatment in fee-for-service Medicaid, often with prior authorization requirements (KFF, 2024).
- Employer coverage is evolving, but employers cite cost concerns and may tighten requirements (based on findings from the 2025 KFF Employer Health Benefits Survey and related interviews) (KFF, 2025).
Practical step: ask your prescriber's office what documentation your plan typically wants (BMI, comorbidities, prior attempts, etc.) and whether an appeal is realistic.
"If I choose either one, how do I make results better?" (the muscle-sparing playbook)
Medication is a tailwind—not the whole engine. If you want the best-looking and best-feeling outcome, protect lean mass.
- Set a protein target you can hit consistently. Most exercising adults do well in the 1.4–2.0 g/kg/day range (ISSN Position Stand).
- Lift 2–4x/week. (Even "minimum effective" strength training beats none.)
- Track body composition, not just scale weight. A DEXA scan can show whether your weight loss is mostly fat, or if lean mass is dropping faster than you'd like.
If you're worried about muscle loss during GLP-1 therapy, read: Ozempic muscle loss: how to prevent lean mass reduction.
And if your main health goal is reducing deep belly fat, see: The impact of weight loss on visceral fat (BodySpec data).
FAQ: Zepbound vs Wegovy
Is Zepbound "stronger" than Wegovy?
In a head-to-head randomized trial, tirzepatide led to greater average weight loss than semaglutide at 72 weeks (−20.2% vs −13.7%) (NEJM, 2025). "Stronger" isn't a formal medical term, but the average effect size was larger.
Do Zepbound and Wegovy have the same side effects?
They overlap heavily (GI symptoms are common, and both have a thyroid tumor boxed warning based on rodent data), but the labeling details differ (e.g., Zepbound's oral contraceptive guidance) (Zepbound FDA label; Wegovy FDA label).
Which is better for heart health?
Wegovy's label includes an indication to reduce major cardiovascular events in certain adults with established cardiovascular disease and obesity/overweight (Wegovy FDA label). Discuss your personal cardiovascular history with a clinician.
Which is better if I have sleep apnea?
Zepbound is indicated for moderate-to-severe obstructive sleep apnea in adults with obesity (Zepbound FDA label).
Is there a pill version of Wegovy?
Yes—the FDA has approved a once-daily oral Wegovy tablet (NPR; NBC News). In clinical trials, average weight loss with the pill was roughly 13% to 17% of starting body weight over ~64–68 weeks. The pill must be taken on an empty stomach with water, followed by a 30-minute wait before eating or drinking. For full details, see: Wegovy pills: 2026 guide to approval, cost & results.
Is there a pill version of Zepbound?
Not yet. As of now, Zepbound is only available as a once-weekly injection.
How do I know if I'm losing fat instead of muscle?
Use a body composition method that separates fat mass and lean mass—rather than relying on a scale that only shows total weight. DEXA does that, and can also estimate visceral fat (DEXA guide).
Next steps: make your choice measurable
If you're starting (or switching) GLP-1/GIP therapy, consider making your baseline objective:
- Get a baseline DEXA before or near your start date.
- Re-scan in 8–12 weeks (when titration is underway).
- Re-scan after you've been on a stable maintenance dose long enough to see a true trend.
To find the nearest BodySpec location and book, start here: BodySpec scheduling.
If you want deeper dives on each medication:
