Zepbound vs Wegovy - Differences in Weight Loss Drug Comparison

By: Noah W Chung | PharmD

In this comparison between Wegovy vs Zepbound, SaveHealth the prescription discount website explores the differences. Zepbound (tirzepatide) and Wegovy (semaglutide) are FDA-approved injectable medications revolutionizing weight management. Both belong to the incretin mimetic drug class but differ in their mechanisms: Zepbound activates both GLP-1 and GIP receptors, while Wegovy targets only GLP-1. These medications help regulate appetite, slow gastric emptying, and promote satiety, making them powerful tools for chronic weight management in qualified patients.  Learn more and see savings for other GLP-1 agonists on SaveHealth.

Mechanism of Action: Zepbound vs Wegovy Comparison 

Zepbound's dual-action approach may lead to more significant weight loss by simultaneously targeting two hunger-regulating pathways. 

Efficacy and Weight Loss Outcomes: Wegovy vs Zepbound 

Clinical trials demonstrate distinct results: 

• Zepbound: Participants lost 20.2% of body weight on average (50.3 lbs) over 72 weeks in SURMOUNT-5 trials. 

• Wegovy: Average weight loss of 13.7% (33.1 lbs) in similar studies. 

Key secondary outcomes: 

• 64.6% of Zepbound users achieved ≥15% weight loss vs 40.1% with Wegovy 

• Zepbound reduced waist circumference by 7.2 inches vs Wegovy's 5.1 inches 

NEJM-published SURMOUNT-5 trial confirmed Zepbound's superior weight reduction in head-to-head comparison 

FDA-Approved Indications

• Adults with BMI ≥30 (obesity) 

• Adults with BMI ≥27 + at least 1 weight related comorbidity (symptomatic heart failure w/preserved ejection fraction, metabolic dysfunction associated steatohepatitis)

• Moderate-to-severe obstructive sleep apnea management with obesity

Wegovy: 

• Adults + adolescents (12+) with obesity (BMI ≥30) 

• Overweight adults (BMI ≥27)

• Cardiovascular risk reduction in adults with heart disease 

Wegovy holds broader pediatric approval, while Zepbound offers OSA-specific indications Dosage and Administration 

Zepbound Titration: 

• Start: 2.5mg weekly × 4 weeks 

• Increase by 2.5mg monthly → Maintenance: 5mg, 10mg, or 15mg 

Wegovy Titration: 

• Start: 0.25mg weekly × 4 weeks 

• Gradual escalation over 16-20 weeks → Maintenance: 1.7mg or 2.4mg 

Wegovy vs Zepbound - Safety Profile and Side Effects 

Common adverse effects (% incidence):

Serious risks include pancreatitis, gallbladder issues, and thyroid C-cell tumors (boxed warning for both). Wegovy shows higher rates of hypoglycemia in diabetes patients. 

Zepbound vs Wegovy - Patient Considerations 

Ideal Candidates: 

• Zepbound: Adults needing >15% weight loss with metabolic comorbidities 

• Wegovy: Patients prioritizing cardiovascular protection or requiring pediatric use

Contraindications: 

• Personal/family history of medullary thyroid carcinoma 

• Multiple endocrine neoplasia type 2 

• Severe GI disease 

Novant Health emphasizes comprehensive care - medications work best with dietary changes + exercise regimens 

Long-Term Use and Discontinuation 

• Both medications require ongoing use to maintain weight loss 

• Abrupt cessation may lead to: 

  • Weight regain (70-80% of lost weight within 1 year) 

  • Rebound hunger 

  • Metabolic changes 

• Tapering protocols recommended under medical supervision 

Lilly's 2025 data shows Zepbound maintains efficacy for 2+ years with continuous use

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