What is the mean weight loss with Ozempic (semaglutide) compared to other weight loss medications?

Mean Weight Loss: Ozempic vs Zepbound

Zepbound (tirzepatide) achieves superior weight loss of 20.9% compared to Ozempic (semaglutide 2.4mg) at 14.9%, representing a 6% absolute advantage at 72 weeks. 1

Direct Comparison Data

Tirzepatide demonstrates a mean difference of 4.23kg greater weight loss compared to semaglutide (95% CI: 3.22-5.25kg), with high strength of evidence supporting this superiority. 1

Specific Weight Loss Outcomes

Ozempic (Semaglutide 2.4mg weekly):

• Mean weight loss: 14.9% at 68 weeks in patients without diabetes 1, 2, 3
• Absolute weight loss: -12.3kg to -15.3kg from baseline 4, 3
• 69% of patients achieved ≥10% weight loss 2
• 51-64% achieved ≥15% weight loss 2
• 33.4% achieved ≥20% weight loss 4

Zepbound (Tirzepatide 15mg weekly):

• Mean weight loss: 20.9% at 72 weeks 1
• Represents 6.5% additional weight loss compared to semaglutide 2.4mg 1
• Superior cardiometabolic benefits including greater waist circumference reduction, triglyceride reduction, and fasting glucose control 1

Clinical Context for Weight Loss Differences

The dual-receptor mechanism of tirzepatide (GIP + GLP-1) provides enhanced metabolic benefits including more potent appetite suppression, delayed gastric emptying, and improved insulin secretion compared to semaglutide's single GLP-1 receptor action. 1

Weight Loss in Special Populations

Patients with type 2 diabetes experience lower weight loss with both medications:

• Semaglutide in diabetic patients: 4-9.6% weight loss 1, 2
• Weight loss appears consistently lower in individuals with diabetes compared to those without diabetes 1

For patients with diabetes specifically, Ozempic 1mg (the diabetes-approved dose) produces:

• Mean weight loss: -3.8kg to -5.5kg at 56 weeks 5
• This is substantially less than the 2.4mg obesity-approved dose 5

Practical Prescribing Implications

Tirzepatide should be prioritized as first-line therapy for obesity management due to its greatest weight loss magnitude and superior cardiometabolic benefits, with semaglutide 2.4mg as second choice if tirzepatide is unavailable or not tolerated. 1

For patients with established cardiovascular disease, semaglutide 2.4mg may be preferred despite lower weight loss, as it has proven cardiovascular outcome benefits with 20% reduction in composite cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80). 1

Dosing Considerations

Semaglutide titration schedule:

• Start 0.25mg weekly for 4 weeks
• Increase to 0.5mg weekly for 4 weeks
• Increase to 1.0mg weekly for 4 weeks
• Increase to 1.7mg weekly for 4 weeks
• Maintenance dose: 2.4mg weekly after 16 weeks 1

Tirzepatide titration schedule:

• Start 5mg weekly (FDA-approved starting dose) 1
• Titrate upward every 4 weeks based on tolerance
• Maximum dose: 15mg weekly 1

Safety Profile Comparison

Both medications share similar gastrointestinal adverse event profiles:

• Nausea: 17-22% with tirzepatide vs 18-40% with semaglutide 1
• Diarrhea: 13-16% with tirzepatide vs 12% with semaglutide 1
• Vomiting: 6-10% with tirzepatide vs 8-16% with semaglutide 1

Semaglutide has higher treatment discontinuation rates with 34 more discontinuations per 1000 patients compared to placebo, primarily from gastrointestinal effects. 1

Both medications carry identical contraindications: personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, with shared risks of pancreatitis and gallbladder disease. 1

Cost Considerations

Average wholesale prices are comparable:

• Semaglutide: approximately $1,600 per 30-day supply 1
• Tirzepatide: approximately $1,272 per 30-day supply 1
• Tirzepatide faces more insurance authorization barriers despite lower cost 1