Tirzepatide
Dual GIP/GLP-1 Receptor AgonistFDA-approvedAlso known as: Mounjaro, Zepbound, LY3298176
A first-in-class dual GIP/GLP-1 receptor agonist that produces up to 22.5% body weight loss, approved for type 2 diabetes and obesity management.
Overview
Tirzepatide is a novel dual-action peptide developed by Eli Lilly that simultaneously activates both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. Approved as Mounjaro for type 2 diabetes (2022) and Zepbound for chronic weight management (2023), tirzepatide has demonstrated the most potent weight loss of any approved medication, with average reductions of 20-22.5% body weight in clinical trials. The dual-agonist approach represents a significant advance over single GLP-1 receptor agonists, as GIP receptor activation provides complementary metabolic benefits including enhanced fat oxidation, improved insulin sensitivity, and potentially better tolerability. Tirzepatide is administered once weekly via subcutaneous injection and has rapidly become one of the most sought-after obesity treatments worldwide.
Mechanism of Action
Tirzepatide acts as a dual incretin agonist: (1) GLP-1 receptor activation suppresses appetite centrally, slows gastric emptying, and stimulates glucose-dependent insulin secretion; (2) GIP receptor activation enhances insulin secretion, improves fat metabolism, may increase energy expenditure, and appears to improve tolerability of GI side effects; (3) Suppresses glucagon in a glucose-dependent manner; (4) Improves insulin sensitivity in peripheral tissues including adipose and muscle; (5) Reduces hepatic fat content, showing promise for MASH/NASH; (6) The combined GIP/GLP-1 action produces synergistic effects on weight loss and metabolic parameters beyond what either pathway achieves alone.
Molecular Formula
C225H348N48O68
Molecular Weight
4813.45 g/mol
Sequence
Modified GIP analog with GLP-1 receptor activity (39 amino acids with C20 fatty diacid moiety)
Dosage Protocols
Dose Range
2.5mg – 15mg
Frequency
Once weekly
Route
subcutaneous
Cycle Length
Ongoing (chronic therapy)
Start at 2.5mg for 4 weeks, then increase to 5mg. May increase by 2.5mg increments every 4 weeks to max of 15mg. Available in 2.5, 5, 7.5, 10, 12.5, and 15mg doses.
Source: FDA prescribing information (Mounjaro)
Side Effects
| Effect | Severity |
|---|---|
| Nausea | moderate |
| Diarrhea | mild |
| Vomiting | moderate |
| Constipation | mild |
| Decreased appetite | mild |
| Injection site reactions | mild |
| Pancreatitis | severe |
| Thyroid C-cell tumors | severe |
Pros & Cons
Produces the most significant weight loss of any approved drug — up to 22.5% in SURMOUNT-1
Dual GIP/GLP-1 mechanism may provide superior metabolic benefits and better GI tolerability vs GLP-1 alone
Once-weekly dosing with convenient auto-injector pen
Significant improvements in HbA1c, blood pressure, triglycerides, and liver fat
Over 50% of participants in weight loss trials achieved ≥20% body weight reduction
GI side effects remain common, particularly during dose escalation
Very expensive without insurance ($1,000-1,100/month) with limited weight-loss coverage
Significant supply constraints since launch
Lean muscle mass loss accompanies fat loss; resistance training essential
Long-term safety data beyond 2 years is still limited
Research Studies
Legal Status
FDA-approved for type 2 diabetes (Mounjaro, May 2022) and chronic weight management (Zepbound, November 2023). Prescription required. Insurance coverage varies by indication.
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