What is the difference between Mounjaro (tirzepatide) and Ozempic (semaglutide)?

Mounjaro vs Ozempic: Key Differences

Mounjaro (tirzepatide) demonstrates superior glycemic control and weight reduction compared to Ozempic (semaglutide), with tirzepatide achieving greater HbA1c reductions and approximately 1.9-5.5 kg more weight loss across dose comparisons. 1

Mechanism of Action

• Tirzepatide (Mounjaro) is a dual GIP/GLP-1 receptor agonist, activating both glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors 2, 3
• Semaglutide (Ozempic) is a selective GLP-1 receptor agonist only 2, 1
• Both medications stimulate insulin secretion and reduce glucagon secretion in a glucose-dependent manner, improve satiety, and promote weight loss 2

Glycemic Efficacy

Tirzepatide achieves superior HbA1c reduction across all dose comparisons:

• Tirzepatide 5 mg reduces HbA1c by -2.01 percentage points vs semaglutide 1 mg at -1.86 percentage points (difference -0.15%, P=0.02) 1
• Tirzepatide 10 mg achieves -2.24 percentage points reduction (difference -0.39%, P<0.001) 1
• Tirzepatide 15 mg achieves -2.30 percentage points reduction (difference -0.45%, P<0.001) 1
• Network meta-analysis confirms tirzepatide 15 mg is most efficacious (-21.61 mmol/mol), followed by tirzepatide 10 mg (-20.19 mmol/mol), then semaglutide 2.0 mg (-17.74 mmol/mol) 4

Weight Loss Efficacy

Tirzepatide produces substantially greater weight reduction:

• Tirzepatide 5 mg: 1.9 kg more weight loss than semaglutide 1 mg (P<0.001) 1
• Tirzepatide 10 mg: 3.6 kg more weight loss (P<0.001) 1
• Tirzepatide 15 mg: 5.5 kg more weight loss (P<0.001) 1
• Compared to placebo, tirzepatide achieves 5.27-9.57 kg reduction vs semaglutide's 2.52-4.97 kg reduction 4
• In patients with T2D and obesity/overweight, tirzepatide 15 mg shows statistically significant greater odds of achieving ≥5% and ≥15% weight reduction versus semaglutide 2.4 mg 5

Cardiovascular and Metabolic Benefits

• Tirzepatide 15 mg demonstrates statistically significant improvements in waist circumference, fasting plasma glucose, and triglycerides compared to semaglutide 2.4 mg 5
• Real-world evidence suggests tirzepatide reduces major adverse cardiovascular events (MACE) more than semaglutide (HR 0.86,95% CI 0.74-0.99) in patients with OSA and T2D 6
• Both medications have proven cardiovascular safety, though semaglutide has more established CVOT data showing MACE reduction 2

Safety Profile

Both medications have generally comparable safety profiles:

• Gastrointestinal adverse events are the most common side effects for both drugs (nausea 17-22% tirzepatide vs 18% semaglutide; diarrhea 13-16% vs 12%; vomiting 6-10% vs 8%) 1
• Hypoglycemia rates are low and similar: 0.2-1.7% with tirzepatide vs 0.4% with semaglutide 1
• Neither medication increases risk of serious adverse events or severe hypoglycemia compared to placebo 4
• Both have minimal hypoglycemia risk when used as monotherapy but may increase hypoglycemic potential when combined with insulin or sulfonylureas 2

Dosing and Administration

• Tirzepatide: 5 mg, 10 mg, or 15 mg subcutaneous injection once weekly 1
• Semaglutide (Ozempic): 0.5 mg, 1.0 mg, or 2.0 mg subcutaneous injection once weekly 2, 4
• Both require dose titration to minimize gastrointestinal side effects 2

Clinical Decision-Making

Choose tirzepatide when:

• Maximum glycemic control is needed (HbA1c >2% above goal) 1
• Weight loss is a primary treatment objective 3, 5
• Patient has obesity/overweight with T2D requiring aggressive metabolic intervention 5

Choose semaglutide when:

• Established cardiovascular disease is present and proven MACE reduction is priority 2
• Insurance formulary restrictions limit tirzepatide access 3
• Patient preference favors medication with longer track record 2

Common Pitfalls

• Don't assume equivalent efficacy between these agents—tirzepatide consistently outperforms semaglutide for glycemic and weight outcomes 1
• Avoid combining either medication with DPP-4 inhibitors or other GLP-1 receptor agonists 2
• Monitor for gastrointestinal side effects, particularly during dose escalation, as these are dose-dependent 1
• Consider that cost-effectiveness analyses show variable results depending on comparator and willingness-to-pay thresholds 2