Zepbound vs. Wegovy: Comparing weight loss drugs

Zepbound vs. Wegovy: Comparing weight loss drugs

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.

In this comparison between Wegovy versus Zepbound, SaveHealth, a prescription discount/savings card website, explores the differences between GLP-1 agonists.

Mechanism of action: Zepbound versus 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

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.

New England Journal of Medicine-published SURMOUNT-5 trial confirmed Zepbound's superior weight reduction in a head-to-head comparison.

FDA-approved indications

Zepbound

• Adults with BMI ≥30 (obesity).
• Adults with BMI ≥27 plus at least one weight-related comorbidity (symptomatic heart failure with preserved ejection fraction, metabolic dysfunction-associated steatohepatitis).
• Moderate-to-severe obstructive sleep apnea management with obesity.

Wegovy

• Adults and adolescents (12-plus) with obesity (BMI ≥30).
• Overweight adults (BMI ≥27) plus at least one weight-related comorbidity (symptomatic heart failure with preserved ejection fraction, noncirrhotic metabolic dysfunction associated with moderate to advanced fibrosis).
• 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: 2.5 mg weekly for four weeks.
• Increase by 2.5 mg monthly.
• Maintenance: 5 mg, 10 mg, or 15 mg.

Wegovy Titration

• Start: 0.25 mg weekly for four weeks.
• Gradual escalation over 16-20 weeks.
• Maintenance: 1.7 mg or 2.4 mg.

Common adverse effects (percent 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.

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 and 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 one year), rebound hunger, and metabolic changes.
• Tapering protocols are recommended under medical supervision.

Lilly's 2025 data shows Zepbound maintains efficacy for two-plus years with continuous use.

This story was produced by SaveHealth and reviewed and distributed by Stacker.