Rybelsus vs Zepbound

semaglutide (GLP-1 receptor agonist) vs tirzepatide (Dual GIP and GLP-1 receptor agonist) — a complete side-by-side comparison.

Novo NordiskEli Lilly

Rybelsus weight loss

4.4%

Zepbound weight loss

22.5%

Rybelsus dosing

Once daily

Zepbound dosing

Once weekly

Reviewed by Dr. Elena Vance, DOLast reviewed 4 sources cited

Quick Summary

Rybelsus (semaglutide) and Zepbound (tirzepatide) are both incretin-based therapies. In clinical trials, Zepbound showed greater weight loss (22.5% vs 4.4%).

See the comparison table below for detailed side-by-side data.

Rybelsus vs Zepbound: Full Comparison

FeatureRybelsus(semaglutide)Zepbound(tirzepatide)
Active Ingredientsemaglutidetirzepatide
Drug ClassGLP-1 receptor agonistDual GIP and GLP-1 receptor agonist
ManufacturerNovo NordiskEli Lilly
FDA Approved2019-09-202023-11-08
Approved Indications
  • Type 2 diabetes mellitus (adjunct to diet and exercise)
  • Chronic weight management in adults with BMI ≥30 or ≥27 with at least one weight-related comorbidity (adjunct to diet and exercise)
  • Treatment of moderate-to-severe obstructive sleep apnea in adults with obesity (December 20, 2024)
Routeoralsubcutaneous injection
FrequencyOnce dailyOnce weekly
Starting Dose3 mg daily2.5 mg weekly
Maintenance Dose7 mg or 14 mg daily5 mg, 10 mg, or 15 mg weekly
Max Dose14 mg daily15 mg weekly
Weight Loss (%)4.4%22.5%
A1C Reduction1.4%N/A (not indicated for diabetes)
Key TrialPIONEER 1 (26 weeks)SURMOUNT-1 / SURMOUNT-5 (head-to-head vs semaglutide) (72 weeks)
List Price$935-$1,029/month$1,060-$1,176/month
With Insurance$25-$150/month (varies by plan)$25-$250/month (varies; weight-loss coverage is limited)
Savings Card$10/month (Novo Nordisk savings card, commercially insured)$25/month (Lilly savings card, commercially insured)

Side Effects: Rybelsus vs Zepbound

Side EffectRybelsusZepbound
Nausea11-20%24-33%
Abdominal pain5-11%10-14%
Diarrhea5-10%18-25%
Decreased appetite3-9%Not reported
Vomiting4-8%10-18%
Constipation3-5%13-17%
Pancreatitis (rare)<0.5%<1%
DyspepsiaNot reported7-10%
Injection site reactionNot reported3-7%
Hair lossNot reported5-6%
Gallbladder eventsNot reported1.6%

Severity scale: 1 (mild) to 5 (serious). Based on FDA prescribing information and clinical trial data.

Related Comparisons

Frequently Asked Questions

Sources & References

  1. Rybelsus FDA prescribing information
  2. Zepbound FDA prescribing information
  3. Aroda VR et al., Lancet 2019;394:39-50. FDA prescribing information.
  4. Jastreboff AM et al., N Engl J Med 2022;387:327-340. SURMOUNT-5: Lilly press release May 11, 2025.

This content is for informational purposes only and is not medical advice. Always consult your healthcare provider before making medication decisions. See our full medical disclaimer.