FDA Status: FDA Approved
Tirzepatide: A Comprehensive Scientific Summary
Tirzepatide is the first dual GIP/GLP-1 receptor agonist approved for clinical use. Developed by Eli Lilly, it represents a new class of metabolic therapy that targets two incretin pathways simultaneously.
Mechanism of Action
Tirzepatide works by activating two receptors:
- GLP-1 Receptor: Reduces appetite, slows gastric emptying, and stimulates insulin secretion from the pancreas
- GIP Receptor: Enhances fat metabolism, improves insulin sensitivity in fat tissue, and appears to reduce the nausea commonly associated with GLP-1 drugs
The combination of both pathways creates a synergistic effect — greater weight loss and metabolic improvement than either pathway alone.
How It Differs from Semaglutide
Semaglutide targets only GLP-1 receptors. Tirzepatide targets both GLP-1 and GIP. In head-to-head trials (SURPASS-2), tirzepatide showed superior blood sugar control and greater weight loss compared to semaglutide 1mg.
Clinical Trial Data
SURMOUNT-1 (Obesity without Diabetes)
- 2,539 adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one comorbidity
- 15mg dose: Average weight loss of 20.9% at 72 weeks
- 10mg dose: Average weight loss of 19.5%
- 5mg dose: Average weight loss of 15.0%
SURMOUNT-3 (Intensive Lifestyle + Tirzepatide)
- Participants who first completed a 12-week intensive lifestyle program
- Additional 26.6% total body weight loss with tirzepatide 15mg
SURPASS Trials (Type 2 Diabetes)
- Consistent HbA1c reductions of 2.0-2.5% across doses
- Superior to semaglutide 1mg, insulin glargine, and insulin degludec
Dosage Protocol
Standard Titration Schedule (once weekly subcutaneous injection):
| Month | Dose | Purpose | |-------|------|---------| | 1 | 2.5 mg | Loading/tolerance | | 2 | 5.0 mg | Therapeutic start | | 3 | 7.5 mg | Escalation | | 4 | 10.0 mg | Mid-range | | 5 | 12.5 mg | Escalation | | 6+ | 15.0 mg | Maximum dose |
Dose escalation should only occur under physician guidance.
Safety Profile
Common side effects:
- Nausea (most common, usually improves over time)
- Diarrhea
- Decreased appetite
- Constipation
- Injection site reactions
Serious risks:
- Pancreatitis (rare but reported)
- Gallbladder problems
- Thyroid C-cell tumors (seen in animal studies — carries a boxed warning)
- Hypoglycemia when combined with insulin or sulfonylureas
Contraindications:
- Personal or family history of medullary thyroid carcinoma (MTC)
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
FDA Approval Status
- Mounjaro (type 2 diabetes): FDA approved May 2022
- Zepbound (chronic weight management): FDA approved November 2023
- Available only by prescription
Common Stacks
Tirzepatide is typically used as monotherapy. Some practitioners combine it with:
- TB-500 (for tissue repair during rapid weight loss)
- GHK-Cu (for skin elasticity support)
Profile last updated: July 2025