What are the differences between Ozempic (semaglutide) and Mounjaro (tirzepatide)?

Ozempic vs. Mounjaro: Key Differences

Mounjaro (tirzepatide) delivers superior weight loss (20.9%) compared to Ozempic (semaglutide 1mg for diabetes), but Ozempic has proven cardiovascular benefits that Mounjaro has not yet demonstrated in dedicated outcome trials. 1

Mechanism of Action

Ozempic (semaglutide) is a selective GLP-1 receptor agonist that binds exclusively to GLP-1 receptors in the pancreas, brain, gastrointestinal tract, and other organs, stimulating glucose-dependent insulin secretion and suppressing appetite through hypothalamic pathways. 2

Mounjaro (tirzepatide) is a dual GIP/GLP-1 receptor co-agonist that activates both glucose-dependent insulinotropic polypeptide (GIP) receptors and GLP-1 receptors, producing synergistic effects on insulin secretion, glucagon suppression, appetite reduction, and increased energy expenditure through enhanced lipolysis and lipid oxidation. 2, 3

The dual-receptor activation of tirzepatide provides enhanced metabolic benefits including delayed gastric emptying, suppressed appetite, and improved insulin secretion compared to semaglutide's single-receptor action. 1

Weight Loss Efficacy

Tirzepatide demonstrates markedly superior weight loss:

• Tirzepatide 15mg weekly: 20.9% weight loss at 72 weeks 1
• Semaglutide 1mg weekly (Ozempic): approximately 7.0% weight loss in patients with type 2 diabetes 1
• Semaglutide 2.4mg weekly (Wegovy, not Ozempic): 14.9% weight loss at 68 weeks 1

The mean difference in weight loss between tirzepatide and semaglutide is 4.23kg (95% CI: 3.22-5.25), representing a clinically significant advantage. 4 This weight loss effect is dose-dependent for both medications. 1

Nearly 40% of patients achieve ≥25% total body weight loss with tirzepatide 15mg, compared to lower proportions with semaglutide. 1

Glycemic Control

Tirzepatide achieves superior HbA1c reduction:

• Tirzepatide: HbA1c reductions of 1.87-2.59% across doses, with 23.0-62.4% of patients achieving HbA1c <5.7% (normal range) 3
• Semaglutide 1mg: HbA1c reduction of approximately 1.4-1.48% 1

In head-to-head comparison, tirzepatide demonstrated superior HbA1c reduction compared to semaglutide 1mg, with a treatment difference of -0.45% (95% CI: -0.57 to -0.32; P<0.001). 5

Cardiovascular Benefits

This is where Ozempic has a critical advantage:

Semaglutide has proven cardiovascular benefit with a 26% reduction in composite cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.74,95% CI 0.58-0.95) in the SUSTAIN-6 trial. 1 Semaglutide 2.4mg also demonstrated a 20% reduction (HR 0.80) in the SELECT trial for patients with cardiovascular disease and BMI ≥27. 1

Tirzepatide has demonstrated cardiovascular safety (MACE-4 hazard ratios <1.0 with upper confidence bounds <1.3), but does not reduce all-cause mortality compared to usual care and lacks dedicated cardiovascular outcome trial data showing benefit. 1, 3

For patients with established cardiovascular disease, semaglutide 2.4mg (Wegovy) should be prioritized over tirzepatide due to proven cardiovascular risk reduction. 1

Cardiometabolic Advantages of Tirzepatide

Beyond weight loss, tirzepatide shows statistically significant advantages over semaglutide including:

• Greater waist circumference reduction 1
• Superior triglyceride reduction 1
• Better fasting glucose control 1
• Broader cardiometabolic improvements including blood pressure reduction and liver fat reduction 1

Administration and Dosing

Both medications are administered as subcutaneous injections once weekly. 1

Ozempic (semaglutide) dosing:

• Starting dose: 0.25mg weekly for 4 weeks 1
• Maintenance for diabetes: typically 0.5mg or 1.0mg weekly 1

Mounjaro (tirzepatide) dosing:

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

Slow titration is essential for both medications to minimize gastrointestinal side effects. 1

Side Effects and Safety

Both medications share similar adverse effect profiles:

• Gastrointestinal effects predominate: nausea (17-22% tirzepatide, 18-40% semaglutide), diarrhea (13-16% tirzepatide, 12% semaglutide), vomiting (6-10% tirzepatide, 8-16% semaglutide) 1, 5
• These effects are typically mild-to-moderate, dose-dependent, and decrease over time 1, 3

Serious but rare risks (identical for both):

• Pancreatitis (causality not definitively established) 1
• Gallbladder disease (cholelithiasis, cholecystitis) 1
• Minimal hypoglycemia risk when used as monotherapy 1

Absolute contraindication for both: Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2). 1, 2

Semaglutide has higher discontinuation rates due to adverse events, with 34 more discontinuations per 1000 patients compared to placebo. 1

Cost Considerations

• Semaglutide (Ozempic): approximately $1,600 per 30-day supply 1
• Tirzepatide (Mounjaro): approximately $1,272 per 30-day supply 1

Both require long-term financial planning, and insurance authorization may be challenging, particularly for obesity management without diabetes. 1

Clinical Decision Algorithm

Choose Mounjaro (tirzepatide) when:

• Maximum weight loss is the primary goal (BMI ≥30 or ≥27 with comorbidities) 1
• Patient has type 2 diabetes requiring aggressive glycemic control (HbA1c ≥1.5% above goal) 1
• No established cardiovascular disease is present 1
• Broader cardiometabolic benefits (triglycerides, waist circumference) are priorities 1

Choose Ozempic/Wegovy (semaglutide) when:

• Patient has established cardiovascular disease requiring proven cardiovascular protection 1
• Patient has chronic kidney disease (longer-term renal outcome data available) 1
• Cardiovascular risk reduction is the priority over maximum weight loss 1

For type 2 diabetes with obesity, prioritize tirzepatide over semaglutide 1mg (Ozempic) due to greater HbA1c reduction and superior weight loss. 1 However, for patients with established cardiovascular disease, consider semaglutide 2.4mg (Wegovy, not Ozempic) for proven cardiovascular benefit. 1

Important Caveats

Both medications must be used in conjunction with lifestyle modifications (reduced-calorie diet, minimum 150 minutes/week physical activity) for optimal results. 1

After cessation of either medication, significant weight regain occurs—patients regain one-half to two-thirds of lost weight within 1 year, highlighting the need for lifelong treatment. 1

No dose adjustment is required for either medication across all stages of chronic kidney disease, including eGFR <30 mL/min/1.73 m². 1

When initiating either medication in patients on insulin or sulfonylureas, reduce these agents by 20-50% to prevent hypoglycemia. 1