Tirzepatide
Also known as: Mounjaro, Zepbound, LY3298176
A dual GLP-1/GIP receptor agonist developed by Eli Lilly, FDA-approved for both Type 2 diabetes (Mounjaro) and obesity (Zepbound), showing up to 22.5% weight loss in trials.
Quick Facts
What Is Tirzepatide?
Tirzepatide is a first-in-class dual GLP-1/GIP receptor agonist developed by Eli Lilly and Company. It is marketed under two brand names: Mounjaro (approved for Type 2 diabetes in May 2022) and Zepbound (approved for chronic weight management in November 2023). It represents a significant advancement over single-agonist GLP-1 drugs like semaglutide.
What makes tirzepatide unique is its dual mechanism. While drugs like semaglutide (Ozempic/Wegovy) only activate the GLP-1 receptor, tirzepatide activates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors. This dual activation produces greater weight loss and metabolic improvements than GLP-1 agonists alone, as demonstrated in multiple head-to-head clinical trials.
Tirzepatide is a 39-amino acid synthetic peptide based on the GIP sequence, with modifications that allow it to also activate GLP-1 receptors. Its long half-life of approximately 5 days allows for convenient once-weekly dosing.
How Does Tirzepatide Work?
Tirzepatide works through two complementary hormonal pathways:
GLP-1 receptor activation: GLP-1 (glucagon-like peptide-1) is an incretin hormone released by the gut after eating. Activating GLP-1 receptors in the brain reduces appetite and increases feelings of fullness (satiety). In the pancreas, it stimulates insulin secretion and suppresses glucagon release, improving blood sugar control. GLP-1 activation also slows gastric emptying, meaning food stays in the stomach longer, contributing to reduced food intake.
GIP receptor activation: GIP (glucose-dependent insulinotropic polypeptide) is another incretin hormone. While its role in weight management is still being fully understood, GIP receptor activation appears to enhance the effects of GLP-1, improve insulin sensitivity in fat tissue, potentially influence fat metabolism and distribution, and work synergistically with GLP-1 signaling to amplify appetite suppression.
Combined effects: The dual activation creates a more powerful metabolic intervention than either pathway alone. Clinical trials consistently show that tirzepatide produces greater weight loss, better blood sugar control, and more significant improvements in cardiometabolic risk factors compared to GLP-1-only drugs.
Effects on body composition: Research indicates that approximately 70-80% of weight lost on tirzepatide is fat mass, with 20-30% being lean mass. This ratio is comparable to weight loss from caloric restriction alone, though ongoing research is examining whether concurrent resistance training can improve lean mass preservation.
Clinical Trial Results
SURMOUNT-1 (Obesity, no diabetes): The pivotal weight loss trial enrolled 2,539 adults with BMI ≥30 (or ≥27 with comorbidities). At 72 weeks:
- 15 mg dose: -22.5% mean body weight loss (vs -2.4% placebo)
- 10 mg dose: -21.4% mean weight loss
- 5 mg dose: -16.0% mean weight loss
- Over 90% of participants lost at least 5% body weight
- 63% of participants at the 15 mg dose lost at least 20%
SURPASS-2 (Head-to-head vs semaglutide 1mg): Tirzepatide at all doses (5, 10, 15 mg) produced greater reductions in HbA1c and body weight compared to semaglutide 1 mg in patients with Type 2 diabetes. The 15 mg tirzepatide group lost 12.4 kg vs 6.2 kg for semaglutide 1 mg.
SURMOUNT-2 (Obesity with Type 2 diabetes): Mean weight loss of 14.7% (15 mg) at 72 weeks, significantly exceeding placebo.
Additional findings: Tirzepatide has shown benefits for obstructive sleep apnea (SURMOUNT-OSA), heart failure with preserved ejection fraction (SUMMIT), and non-alcoholic steatohepatitis (SYNERGY-NASH), suggesting broad cardiometabolic benefits beyond weight loss.
Tirzepatide Dosage Chart
Tirzepatide uses a gradual dose-escalation protocol to minimize gastrointestinal side effects:
| Phase | Dose | Duration | Notes |
|---|---|---|---|
| Starting dose | 2.5 mg/week | Weeks 1-4 | Initiation dose (not a maintenance dose) |
| First escalation | 5 mg/week | Weeks 5-8 | First effective dose; some patients may stay here |
| Second escalation | 7.5 mg/week | Weeks 9-12 | Intermediate dose if tolerating well |
| Third escalation | 10 mg/week | Weeks 13-16 | Many patients see optimal results here |
| Fourth escalation | 12.5 mg/week | Weeks 17-20 | Intermediate to maximum dose |
| Maximum dose | 15 mg/week | Week 21+ | Maximum approved dose for best results |
Key dosing notes: The 2.5 mg starting dose is not intended for ongoing treatment — it exists solely to allow the body to adjust. Dose increases should occur no sooner than every 4 weeks. If side effects are intolerable at a new dose, it is common to step back to the previous dose for another 4 weeks before re-attempting escalation. The injection is administered once weekly on the same day each week, at any time of day, with or without meals.
Side Effects & Safety
Most common side effects (occurring in >5% of participants):
- Nausea (12-31%, dose-dependent) — most common during dose escalation, typically improves over time
- Diarrhea (12-23%)
- Decreased appetite (this is partly the therapeutic mechanism)
- Vomiting (5-14%)
- Constipation (6-12%)
- Injection site reactions (mild, typically transient)
Serious warnings (from prescribing information):
- Thyroid C-cell tumors: Boxed warning based on rodent studies showing thyroid C-cell tumors with GLP-1 agonists. Not confirmed in humans but contraindicated in patients with personal/family history of medullary thyroid carcinoma or MEN 2.
- Pancreatitis: Cases of acute pancreatitis have been reported. Discontinue if pancreatitis is suspected.
- Gallbladder problems: Rapid weight loss increases gallstone risk. Report symptoms of gallbladder disease.
- Hypoglycemia: Risk increases when used with insulin or sulfonylureas.
Drug interactions: Tirzepatide's effect on gastric emptying may affect absorption of oral medications. Of particular note, oral contraceptives may be less effective during the first 4 weeks and any dose escalation period — alternative contraception is recommended.
Tirzepatide vs Semaglutide: Key Differences
The two most commonly compared weight loss medications differ in important ways:
| Factor | Tirzepatide | Semaglutide |
|---|---|---|
| Mechanism | Dual agonist (GLP-1 + GIP) | Single agonist (GLP-1 only) |
| Max weight loss (trials) | ~22.5% at 72 weeks | ~15.2% at 68 weeks |
| Brand names | Mounjaro / Zepbound | Ozempic / Wegovy |
| Dosing | Once weekly (SC) | Once weekly (SC) |
| Max dose | 15 mg | 2.4 mg (Wegovy) |
| Time on market | Since 2022 | Since 2017 |
| Developer | Eli Lilly | Novo Nordisk |
For a complete head-to-head analysis, see our dedicated Tirzepatide vs Semaglutide comparison page.
Frequently Asked Questions About Tirzepatide
Yes. Tirzepatide is the active ingredient. Mounjaro is the brand name for tirzepatide approved for Type 2 diabetes, while Zepbound is the brand name for tirzepatide approved specifically for weight management. Same drug, different brand names for different indications.
Clinical trials showed average weight loss of 22.5% at the highest dose (15 mg) over 72 weeks. For a 250 lb person, that translates to roughly 56 lbs. Individual results vary significantly based on dose, diet, exercise, and starting weight.
Head-to-head trial data (SURPASS-2) and cross-trial comparisons suggest tirzepatide produces greater weight loss than semaglutide. This is likely due to the addition of GIP receptor activation. However, both are effective medications and individual response varies.
Treatment starts at 2.5 mg weekly and escalates every 4 weeks: 2.5 → 5 → 7.5 → 10 → 12.5 → 15 mg. The maximum approved dose is 15 mg weekly. Most weight loss occurs at doses of 10 mg and above.
Most patients begin noticing reduced appetite within the first 1-2 weeks. Meaningful weight loss typically becomes apparent by weeks 4-8. The full effect builds over the entire 20+ week escalation period, with maximum results seen after 6-12 months at the target dose.
As of early 2026, compounding pharmacies had been producing tirzepatide under the FDA shortage provisions. However, the regulatory landscape around compounded tirzepatide has been evolving. Check current FDA guidance for the latest status of tirzepatide compounding availability.
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Disclaimer: This article is for informational and educational purposes only. It is not intended as medical advice. The information presented is based on published research and should not be used as a substitute for professional medical guidance. Always consult a qualified healthcare provider before starting any peptide protocol. Some peptides discussed may not be approved for human use by the FDA or equivalent regulatory bodies.