What is the difference between Tirzepatide (dual GIP and GLP-1 receptor agonist) and Zepbound (tirzepatide)?

Tirzepatide vs. Zepbound: Understanding the Difference

Tirzepatide and Zepbound are the same medication - Zepbound is simply the brand name for tirzepatide when prescribed specifically for weight management, while the same molecule is marketed as Mounjaro when used for type 2 diabetes treatment. 1

Mechanism of Action

Tirzepatide is a novel synthetic peptide with dual-hormone agonistic activity that works by:

• Acting as a GLP-1 (glucagon-like peptide-1) receptor agonist, similar to medications like semaglutide
• Additionally activating the GIP (glucose-dependent insulinotropic polypeptide) receptor 1, 2
• This dual-receptor activation mechanism distinguishes it from single-target GLP-1 receptor agonists like semaglutide and liraglutide 3

Clinical Efficacy

Tirzepatide demonstrates superior efficacy compared to single GLP-1 receptor agonists:

• Produces greater weight loss (20.9% at 15mg dose over 72 weeks) compared to semaglutide (15.1% with subcutaneous semaglutide) 1
• Meta-analyses show tirzepatide 15mg weekly provides 5.1% more weight loss than semaglutide 2.4mg weekly 1
• Achieves greater HbA1c reductions (2.01-2.30%) compared to semaglutide (1.86%) 3, 2
• A significant proportion of patients (23.0-62.4%) can achieve normoglycemia (HbA1c <5.7%) 2

Administration and Dosing

• Both Zepbound and tirzepatide are administered as once-weekly subcutaneous injections 1, 2
• Available in doses of 5mg, 10mg, and 15mg 2, 4
• Tirzepatide was FDA approved for obesity treatment in November 2023 (as Zepbound) 1

Pharmacological Properties

• Tirzepatide shows an imbalanced mechanism of action with greater engagement of the GIP receptor than the GLP-1 receptor 5
• At the GLP-1 receptor, tirzepatide demonstrates biased signaling, favoring cAMP generation over β-arrestin recruitment 5
• This unique signaling profile may contribute to its enhanced efficacy for insulin secretion 5
• The molecule is an acylated peptide engineered to bind to albumin, allowing for once-weekly dosing 6

Side Effects and Safety

• Similar adverse event profile to GLP-1 receptor agonists
• Most common side effects are gastrointestinal: nausea, vomiting, diarrhea, and constipation 2, 4
• Gastrointestinal side effects are dose-dependent and can be mitigated with slow dose titration 3
• Cardiovascular safety has been demonstrated in clinical trials, with no increased risk of major adverse cardiovascular events 2

Clinical Applications

• Tirzepatide (as Zepbound) is indicated for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity 1
• The same molecule (as Mounjaro) is indicated for improving glycemic control in adults with type 2 diabetes 4
• Shows promise for treating metabolic dysfunction-associated steatotic liver disease (MASLD) 1, 3
• May offer benefits for cardiovascular risk reduction, though dedicated cardiovascular outcome trials are ongoing 2

Key Differences from Other GLP-1 Agonists

• Dual-receptor mechanism (GIP + GLP-1) versus single-receptor targeting 3, 2
• Greater weight loss efficacy compared to semaglutide and liraglutide 1, 3
• Superior glycemic control compared to other GLP-1 receptor agonists 3, 2
• Unique biased signaling properties at the GLP-1 receptor 5

In summary, tirzepatide represents a significant advancement in incretin-based therapies with its dual-receptor mechanism providing superior efficacy for both weight management and glycemic control compared to traditional GLP-1 receptor agonists.