Zepbound vs Wegovy: Complete Comparison
Both Zepbound and Wegovy are FDA-approved weight loss medications that work by mimicking glucagon-like peptide-1 (GLP-1). However, they have different mechanisms, clinical efficacy, and dosing schedules. This comprehensive guide compares both drugs to help you understand which might be better for your situation.
Overview: What Are Zepbound and Wegovy?
Zepbound and Wegovy represent two of the most effective weight loss medications available today. Both are injectable medications approved by the FDA for chronic weight management in adults with obesity or overweight with weight-related health conditions.
Zepbound is the brand name for tirzepatide when used for weight loss. Tirzepatide is also sold as Mounjaro for type 2 diabetes management. Zepbound was approved by the FDA in November 2023.
Wegovy is the brand name for semaglutide when used specifically for weight loss. Semaglutide is also sold as Ozempic for type 2 diabetes management. Wegovy was approved by the FDA in June 2021, making it one of the earlier GLP-1 receptor agonists approved for chronic weight management.
How Zepbound and Wegovy Work: Mechanism of Action
While both are GLP-1 receptor agonists, they have slightly different mechanisms of action that explain some differences in efficacy and side effects.
Zepbound (Tirzepatide): Dual GLP-1/GIP Agonist
Zepbound is a dual agonist, meaning it activates receptors for both GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). This dual mechanism makes it more potent than single GLP-1 agonists.
- GLP-1 activation reduces appetite and increases feelings of fullness
- GIP activation enhances energy expenditure and improves glucose control
- Combined effect leads to greater weight loss and metabolic improvements
Wegovy (Semaglutide): Single GLP-1 Agonist
Wegovy activates only GLP-1 receptors. While less complex than Zepbound's dual mechanism, it's still highly effective for weight loss and metabolic health.
- GLP-1 activation slows gastric emptying
- Reduces appetite through central nervous system signaling
- Improves insulin secretion and glucose metabolism
Clinical Trial Results: SURMOUNT vs STEP
The most compelling evidence comes from head-to-head clinical trial data. Zepbound's efficacy was demonstrated through the SURMOUNT trials, while Wegovy's was demonstrated through the STEP trials.
SURMOUNT Trials (Zepbound/Tirzepatide)
- SURMOUNT-3: 21.4% average weight loss at 15 mg dose (n=731)
- SURMOUNT-2: 21% average weight loss (n=639)
- SURMOUNT-1: 22.5% average weight loss at highest dose
- Duration: 68 weeks of treatment
- Comparison: Superior to semaglutide in head-to-head studies
STEP Trials (Wegovy/Semaglutide)
- STEP-4: 17.4% average weight loss at 2.4 mg dose (n=803)
- STEP-3: 17.6% average weight loss (n=611)
- STEP-2: 10.1% average weight loss at lower doses
- STEP-1: First Phase 3 trial showing 15.3% weight loss
- Duration: Similar 68-week treatment period
Weight Loss Efficacy: Head-to-Head Comparison
Based on clinical trial data, Zepbound produces numerically greater weight loss than Wegovy at equivalent time points. However, both medications are highly effective, and individual results vary significantly.
Key Findings:
- Zepbound: ~21-22.5% average weight loss
- Wegovy: ~17-17.4% average weight loss
- Difference: Approximately 4-5% in favor of Zepbound
- Individual variation: Some patients on Wegovy lose 20%+, others lose 5-10%
- Duration needed: Full effects typically seen after 4-6 months of treatment
It's crucial to understand that average weight loss doesn't predict individual outcomes. Your genetics, baseline weight, adherence to lifestyle changes, and metabolism significantly influence results with either medication.
Dosing Schedules and Titration
Both medications require a gradual dose increase to minimize side effects. However, their dosing schedules differ significantly.
Zepbound (Tirzepatide) Dosing
- Starting dose: 2.5 mg injected subcutaneously once weekly
- Maintenance dose: Increases by 2.5 mg every 4 weeks
- Available doses: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg
- Max recommended dose: 15 mg weekly
- Injection volume: Single-dose pen (pre-filled)
Wegovy (Semaglutide) Dosing
- Starting dose: 0.25 mg injected subcutaneously once weekly
- Titration: Increases by 0.25 mg every week for 4 weeks, then 0.5 mg increments
- Available doses: 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg
- Max recommended dose: 2.4 mg weekly
- Injection volume: Multi-dose pen (5 pens per month) or pre-filled pens
Note: Zepbound uses higher doses but similar efficacy, suggesting greater potency. Wegovy requires a longer titration period, which can delay reaching therapeutic doses.
Side Effects and Tolerability
Both medications have similar side effect profiles. Gastrointestinal symptoms are most common, especially during titration phases.
Common Side Effects (Both Medications)
- Nausea: 25-40% of patients (most common, usually transient)
- Vomiting: 5-12% of patients
- Diarrhea: 20-23% of patients
- Constipation: 15-20% of patients
- Abdominal pain: 15% of patients
- Decreased appetite: Desired effect, but can be excessive
Serious Adverse Events
- Pancreatitis: Rare but serious; discontinue immediately if suspected
- Severe allergic reactions: Very rare
- Gallbladder issues: May increase risk with rapid weight loss
- Hypoglycemia: If combined with diabetes medications
- Retinopathy: Possible in diabetic patients (requires monitoring)
Side effects are typically dose-dependent and often improve after the first 2-4 weeks on each dose. Taking medication with food, staying hydrated, and eating smaller meals can help manage GI symptoms.
Cost and Insurance Coverage
Pricing and insurance coverage are critical factors in choosing between these medications. Both have similar costs, but coverage varies widely by insurance plan.
Retail Pricing (Without Insurance)
- Zepbound: Approximately $1,350-$1,450 per month (4 pens)
- Wegovy: Approximately $1,320-$1,400 per month (4 pens)
- Difference: Negligible; both are expensive
Insurance Coverage
- Most major insurers now cover both medications for weight loss
- Prior authorization often required
- Coverage depends on BMI, comorbidities, and plan-specific criteria
- Medicare does NOT cover weight loss medications
- Medicaid coverage varies by state
Copay Assistance and Discounts
- Novo Nordisk (Wegovy): Offers copay cards reducing costs to $0-$250/month for eligible patients
- Eli Lilly (Zepbound): Offers similar copay reduction programs
- GoodRx: May offer discounts on both medications at certain pharmacies
- Direct discount programs: Some manufacturers offer direct pricing programs
Recommendation: Before choosing based on cost, check with your insurance provider and ask about copay assistance programs. Actual out-of-pocket costs may be $0-$250/month with assistance.
Quick Comparison Table
| Factor | Zepbound (Tirzepatide) | Wegovy (Semaglutide) |
|---|---|---|
| Average Weight Loss | 21-22.5% | 17-17.4% |
| Mechanism | Dual GLP-1/GIP agonist | GLP-1 agonist only |
| Max Dose | 15 mg weekly | 2.4 mg weekly |
| Injection Frequency | Once weekly | Once weekly |
| Titration Period | ~16 weeks (4-week increments) | ~6-8 weeks (weekly increments) |
| Monthly Cost (Uninsured) | $1,350-$1,450 | $1,320-$1,400 |
| Common Side Effects | Nausea, diarrhea, vomiting | Nausea, diarrhea, vomiting |
| FDA Approval for Weight Loss | November 2023 | June 2021 |
| Diabetes Version Available | Mounjaro (T2D) | Ozempic (T2D) |
| Insurance Coverage | Increasingly common | Well-established |
Who Should Choose Zepbound vs Wegovy?
Choose Zepbound If:
- You want maximum weight loss potential (slightly higher average results)
- You prefer rapid dose escalation (reach max dose in 16 weeks vs 8+ weeks)
- You have metabolic concerns beyond weight (GIP activation improves energy expenditure)
- You're willing to use a newer medication with longer-term data still accumulating
Choose Wegovy If:
- You prefer a medication with longer established safety data (approved 2021)
- You want to reach therapeutic doses faster (shorter titration)
- You've already had success with other semaglutide products (Ozempic)
- Your insurance strongly prefers Wegovy with better coverage
Frequently Asked Questions
In clinical trials, Zepbound (tirzepatide) produced greater average weight loss. SURMOUNT-3 showed average weight loss of 21.4% of body weight with Zepbound, while STEP 4 showed 17.4% with Wegovy. However, individual results vary significantly. Both are highly effective GLP-1 receptor agonists.
Yes, many patients switch from Wegovy to Zepbound under medical supervision. However, you should not switch without consulting your doctor. If switching, your doctor may recommend starting at a lower Zepbound dose and titrating up. The two drugs have different mechanisms and dosing schedules, so your injection routine will change.
Both drugs are similarly priced at around $1,350 per month without insurance. However, actual costs depend heavily on your insurance coverage, copay assistance programs, and pharmacy discounts. GLP-1 manufacturers offer copay cards that can reduce out-of-pocket costs to $0-$250/month for eligible patients. Compare actual prices at your pharmacy.
Both have similar side effect profiles. Nausea is most common, affecting 25-40% of patients in clinical trials. The difference is minimal. Side effects are typically dose-dependent and often improve over time. Individual tolerance varies significantly. Some patients tolerate one better than the other for reasons not fully understood.
Both are injected once weekly. Zepbound doses range from 2.5 mg to 15 mg per week. Wegovy doses range from 0.6 mg to 2.4 mg per week. Zepbound requires higher doses but maintains similar efficacy, suggesting it may be a more potent formulation. Both use the same injection frequency.
Insurance coverage depends on your plan and indication. Many plans now cover both for weight loss and obesity treatment. Mounjaro (tirzepatide for diabetes) has different coverage than Zepbound. Prior authorization is often required. Contact your insurance provider directly. Most plans prefer generic alternatives if available, though both are relatively new brand names.
Weight typically returns if the medication is discontinued without maintaining lifestyle changes. Studies show that patients regain 50% of lost weight within 6 months of stopping. Long-term management usually requires continued medication. Maintaining healthy diet and exercise habits can slow rebound weight gain.
Yes, but with caution. Both can lower blood sugar levels. If you have type 2 diabetes and take other medications, your doctor must monitor and adjust doses. Zepbound is specifically approved for weight loss in people with obesity. Some patients with diabetes prefer Mounjaro (tirzepatide for diabetes) instead, which is specifically designed for glucose control.