Ozempic vs. Zepound for Weight Loss
Tirzepatide (Zepbound) demonstrates superior weight loss (20.9%) compared to semaglutide (Ozempic/Wegovy) (14.9%) in clinical trials, making it the more effective option for weight management. 1
Mechanism of Action
- Semaglutide is a GLP-1 receptor agonist that works by stimulating insulin secretion, lowering glucagon secretion, delaying gastric emptying, and inhibiting food intake through actions on the hypothalamus 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 approach to weight management 1
Efficacy Comparison
- Semaglutide 2.4mg weekly demonstrated mean weight loss of 14.9% at 68 weeks in clinical trials (vs 2.4% with placebo) 1, 3
- Tirzepatide 15mg weekly showed greater weight loss of 20.9% in clinical trials, with a mean difference of 4.23kg (95% CI: 3.22-5.25) compared to semaglutide 1
- For semaglutide, 69-79% of participants achieved ≥10% weight loss and 51-64% achieved ≥15% weight loss 4
Administration and Dosing
- Both medications are administered as subcutaneous injections once weekly 1
- Both require gradual dose titration to mitigate gastrointestinal side effects 2, 1
- Semaglutide for obesity management is FDA-approved at 2.4mg weekly (higher than doses used for T2DM alone) 2
- Tirzepatide was FDA approved for obesity treatment in November 2023 1
Side Effects and Safety Profile
- Both medications share similar adverse effect profiles, with gastrointestinal effects predominating, including nausea, vomiting, diarrhea, and constipation 1
- For semaglutide, gastrointestinal adverse events are typically transient, mild-to-moderate in severity, and subside with time 3
- More participants discontinue semaglutide treatment due to gastrointestinal events compared to placebo (4.5% vs. 0.8%) 3
- Both medications are contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 2, 1
- Both are associated with increased risk of pancreatitis and gallbladder disease 2, 1
Cardiovascular Benefits
- Semaglutide has demonstrated cardiovascular benefits, with the SELECT study showing reduced risk of cardiovascular events in patients with obesity 2
- Specifically, semaglutide 2.4mg reduced the composite incidence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR 0.80) in patients with cardiovascular disease and BMI ≥27 1
- Both medications have demonstrated cardiovascular benefits in clinical studies 1
Long-Term Considerations
- Weight regain occurs after discontinuation of semaglutide (11.6% of lost weight regained), highlighting the need for long-term use 2, 1
- Both medications should be used in conjunction with lifestyle interventions (hypocaloric diet and physical activity) for optimal results 2, 1
- Long-term use is necessary as these medications are treating obesity as a chronic disease 1
Special Populations
- Weight loss appears to be lower in individuals with type 2 diabetes compared to those without diabetes for both medications 2, 1
- For patients with type 2 diabetes, both medications offer dual benefits of weight loss and improved glycemic control 1
Cost Considerations
- The average wholesale prices are around $1,600 for a 30-day supply of semaglutide and $1,272 for tirzepatide 1
- Cost and insurance coverage may significantly impact treatment decisions for both medications 1
Clinical Decision Making
- For patients seeking maximum weight loss, tirzepatide would be the preferred option given its superior efficacy 1
- For patients with established cardiovascular disease, semaglutide has robust evidence for cardiovascular risk reduction 2, 1
- Both medications should be considered as long-term treatments, as weight regain occurs after discontinuation 2, 1