What is the difference between Wegovy (semaglutide) and Tirzepatide?

Differences Between Wegovy (Semaglutide) and Tirzepatide

Tirzepatide offers superior weight loss compared to semaglutide (Wegovy), with clinical trials showing 20.9% weight reduction for tirzepatide versus 14.9% for semaglutide. 1, 2

Mechanism of Action

• Semaglutide (Wegovy) is a GLP-1 receptor agonist that acts on the hypothalamus to suppress appetite, delay gastric emptying, increase glucose-dependent insulin release, and decrease glucagon secretion 2
• Tirzepatide is a dual-hormone agonist that acts on both GLP-1 receptors AND glucose-dependent insulinotropic polypeptide (GIP) receptors, providing a more comprehensive metabolic effect 2, 3
• Both medications are administered as subcutaneous injections once weekly 1, 2

Efficacy for Weight Loss

• Tirzepatide 15mg weekly demonstrates superior weight loss (20.9%) compared to semaglutide 2.4mg weekly (14.9%) in clinical trials 1, 2
• Real-world data shows tirzepatide produces mean weight loss of 16.5% versus 14.1% with semaglutide after one year of treatment 4
• Meta-analysis confirms tirzepatide produces significantly greater weight loss than semaglutide (mean difference = 4.23kg; 95% CI: 3.22-5.25) 5
• The weight loss effect appears to be dose-dependent for both medications 1

Glycemic Control (for patients with diabetes)

• Tirzepatide shows greater HbA1c reduction compared to semaglutide in patients with type 2 diabetes 6, 7
• In the SURPASS-2 trial, tirzepatide reduced HbA1c by 2.01-2.30 percentage points compared to 1.86 percentage points with semaglutide 6
• Tirzepatide improves insulin sensitivity and insulin secretory responses to a greater extent than semaglutide 3

Side Effects

• Both medications share similar adverse effect profiles, primarily gastrointestinal in nature 2, 6
• Common side effects include nausea, vomiting, diarrhea, and constipation 1, 6
• Gastrointestinal side effects tend to be mild to moderate and dose-dependent 6
• Both medications have minimal risk for hypoglycemia when used as monotherapy 1

FDA Approval Status

• Semaglutide (Wegovy) 2.4mg weekly was FDA approved for obesity treatment in June 2021 2, 4
• Tirzepatide (Zepbound) was FDA approved for obesity treatment in November 2023 1, 4
• Tirzepatide is also available under the brand name Mounjaro for type 2 diabetes treatment 4

Cardiovascular Benefits

• Both medications have demonstrated cardiovascular benefits 1, 2
• Semaglutide has shown a reduction in the composite incidence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR 0.80) in patients with cardiovascular disease and BMI ≥27 1, 2
• Tirzepatide has shown trends toward cardiovascular event reduction in clinical trials, though dedicated cardiovascular outcome trials are still ongoing 3

Cost Considerations

• Both medications are similar in cost, with average wholesale prices around $1,600 for a 30-day supply of semaglutide and $1,272 for tirzepatide 1
• Insurance coverage may significantly impact out-of-pocket costs for patients 2

Clinical Decision Algorithm

1. For maximum weight loss: Choose tirzepatide (superior weight reduction) 1, 2, 5
2. For patients with type 2 diabetes: Consider tirzepatide (better glycemic control) 6, 7
3. For patients with established cardiovascular disease: Either medication may provide cardiovascular benefits, with more robust evidence currently available for semaglutide 1, 2
4. For patients concerned about injection frequency: Both require once-weekly administration 1, 2

Important Caveats

• Both medications require gradual dose titration to minimize gastrointestinal side effects 2
• Weight regain occurs after discontinuation, highlighting the need for long-term use 2
• Both medications are contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 1, 2
• The full weight loss effect may take several months to achieve with either medication 1, 4