EditorialDrugsZepbound vs Wegovy - Differences in Weight Loss Drug Comparison

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 

Feature 

Zepbound 

Wegovy

Drug Class 

Dual GIP/GLP-1 receptor agonist 

GLP-1 receptor agonist

Hormones Targeted 

GLP-1 + GIP 

GLP-1

Appetite Regulation

Reduces hunger signals via brain + GI

Primarily slows gastric emptying

Metabolic Effects

Enhances insulin sensitivity

Lowers cardiovascular risk

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) + at least 1 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: 2.5mg 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 

Characteristic 

Zepbound 

Wegovy

Time to Max Dose 

12-20 weeks 

16-20 weeks

Injection Sites 

Thigh/Abdomen/Arm 

Thigh/Abdomen/Arm

Missed Dose Protocol 

≤4 days late 

≥2 days between

Common adverse effects (% incidence):

Side Effect 

Zepbound 

Wegovy

Nausea 

12-29% 

16-44%

Diarrhea 

12-23% 

9-30%

Constipation 

6-17% 

3-24%

Injection Site Reactions 

3-8% 

3%

Side Effect 

Zepbound 

Wegovy

Fatigue 

5-7% 

11%

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

Discounts for other GLP-1 Agonists

This article is for educational purposes only and does not substitute for professional medical advice. Always consult your healthcare provider before starting or changing medication.

Recent prescriptions savings

coupons from$10.76Save 52%
coupons from$311.87Save 73%
coupons from$11.52Save 53%
coupons from$4.69Save 80%
coupons from$15.90Save 83%
coupons from$4.44Save 83%
coupons from$5.58Save 78%
coupons from$10.57Save 85%

Free generic prescription coupons

coupons from$5.90Save 93%
coupons from$10.26Save 76%
coupons from$11.19Save 73%
coupons from$6.83Save 84%
coupons from$17.63Save 50%
coupons from$311.87Save 73%
coupons from$2.26Save 92%
coupons from$8.23Save 88%

Free branded prescription coupons

coupons from$7.20Save 78%
coupons from$3687.51Save 82%
coupons from$214.62Save 85%
coupons from$5.61Save 85%
coupons from$48.30Save 71%
coupons from$54.29Save 82%
coupons from$5.27Save 81%
coupons from$8.55Save 86%