What is the dose equivalent of Semaglutide (Glucagon-like peptide-1 (GLP-1) receptor agonist) and Tirzepatide (Dual Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist)?

Dose Equivalency Between Semaglutide and Tirzepatide

Direct Answer: No Established Dose Equivalency Exists

There is no formally established dose equivalency between semaglutide and tirzepatide because they are mechanistically different medications—tirzepatide is a dual GIP/GLP-1 receptor agonist while semaglutide is a selective GLP-1 receptor agonist—and direct dose-to-dose conversion is not clinically appropriate. 1, 2

Comparative Efficacy as a Proxy for "Equivalency"

While true dose equivalency cannot be established, comparative efficacy data from head-to-head trials provides the best available framework for understanding relative potency:

Weight Loss Outcomes

• Tirzepatide 5 mg weekly produces approximately 15.0% weight loss at 72 weeks 3
• Semaglutide 2.4 mg weekly produces approximately 14.9% weight loss at 68 weeks 2
• Tirzepatide 10 mg weekly produces approximately 19.5% weight loss 3
• Tirzepatide 15 mg weekly produces approximately 20.9% weight loss, representing a 6% absolute advantage over semaglutide 2.4 mg 2, 3

Glycemic Control Outcomes

• In direct comparison trials, tirzepatide 5 mg reduced HbA1c by 2.01 percentage points, tirzepatide 10 mg by 2.24 percentage points, and tirzepatide 15 mg by 2.30 percentage points, compared to semaglutide 1.0 mg which reduced HbA1c by 1.86 percentage points 4
• All three tirzepatide doses demonstrated statistical superiority over semaglutide 1.0 mg for HbA1c reduction, with differences ranging from -0.15 to -0.45 percentage points 4
• When compared to semaglutide 2.4 mg in indirect comparisons, tirzepatide 10 mg and 15 mg showed statistically significant greater HbA1c reductions 5

Weight Reduction in Head-to-Head Comparison

• In the SURPASS-2 trial, tirzepatide produced 1.9 kg, 3.6 kg, and 5.5 kg greater weight loss than semaglutide 1.0 mg at the 5 mg, 10 mg, and 15 mg doses respectively 4
• Tirzepatide 15 mg was associated with 6.5% additional weight loss compared to semaglutide 2.4 mg at 72 weeks 2

Practical Clinical Framework

For Weight Loss Prioritization

• If a patient is on semaglutide 2.4 mg weekly and requires greater weight loss, tirzepatide 10-15 mg weekly represents the superior option, not a dose-equivalent alternative 2, 3
• Tirzepatide 5 mg weekly produces roughly comparable weight loss to semaglutide 2.4 mg weekly (15.0% vs 14.9%) 2, 3

For Glycemic Control in Type 2 Diabetes

• Tirzepatide demonstrates dose-dependent superiority across all doses when compared to semaglutide for HbA1c reduction 4, 6
• The magnitude of HbA1c reduction with tirzepatide 5 mg exceeds that of semaglutide 1.0 mg, suggesting tirzepatide's lowest dose is more potent than semaglutide's standard diabetes dose 4, 6

Mechanistic Differences Preclude True Equivalency

• Tirzepatide binds to both GIP and GLP-1 receptors, though its affinity for the GLP-1 receptor is approximately five times less than that of endogenous GLP-1 1, 2
• Semaglutide is a selective GLP-1 receptor agonist with greater albumin affinity, resulting in prolonged action 1
• 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 2

Safety Profile Comparison

• Both medications share similar gastrointestinal adverse event profiles, with nausea occurring in 17-22% with tirzepatide and 18-40% with semaglutide 2
• Diarrhea occurs in 13-16% with tirzepatide and 12% with semaglutide, while vomiting occurs in 6-10% with tirzepatide and 8-16% with semaglutide 2, 4
• Both medications carry identical contraindications for personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 2, 3
• Hypoglycemia risk is minimal with both agents when used as monotherapy, with rates of 0.2-1.7% for tirzepatide and 0.4% for semaglutide 4

Switching Protocol (Not Dose Conversion)

From Semaglutide to Tirzepatide

• Discontinue semaglutide and initiate tirzepatide at 5 mg weekly the following week, regardless of prior semaglutide dose 3
• Follow standard tirzepatide titration: 5 mg weekly for 4 weeks, then increase to 7.5 mg, 10 mg, 12.5 mg, and finally 15 mg weekly based on tolerance and efficacy 3

From Tirzepatide to Semaglutide

• Discontinue tirzepatide and initiate semaglutide at 0.25 mg weekly the following week, regardless of prior tirzepatide dose 2
• Follow standard semaglutide titration over 16 weeks: 0.25 mg (weeks 1-4), 0.5 mg (weeks 5-8), 1.0 mg (weeks 9-12), 1.7 mg (weeks 13-16), and 2.4 mg weekly thereafter 2

Critical Clinical Caveat

The concept of "dose equivalency" between these medications is fundamentally flawed because tirzepatide consistently demonstrates superior efficacy across multiple outcomes at all dose levels when compared to semaglutide. 2, 4, 5, 6 The appropriate clinical question is not "what dose is equivalent?" but rather "which medication and dose best meets this patient's therapeutic goals for weight loss, glycemic control, and cardiovascular risk reduction?" 2