Tirzepatide Guide
Tirzepatide is a dual GIP/GLP-1 receptor agonist marketed as Mounjaro for type 2 diabetes and Zepbound for weight management. In the SURMOUNT-1 trial, participants lost an average of 20.9% body weight at 72 weeks on the highest dose—the most effective weight loss medication tested to date. It's a weekly subcutaneous injection.
What Tirzepatide Is
Tirzepatide is the first dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. It activates both GIP and GLP-1 receptors, two separate gut hormone pathways that regulate appetite, blood sugar, and metabolism.
The FDA approved Mounjaro in May 2022 for type 2 diabetes at doses up to 15mg weekly. In November 2023, Zepbound was approved for chronic weight management at the same dose range. Same active ingredient, different brand names and approved indications.
Manufactured by Eli Lilly. Compounded versions are also available through telehealth providers when brand-name supplies are limited, using the same active ingredient prepared by compounding pharmacies.
How It Works: Dual Mechanism
Unlike semaglutide (GLP-1 only), tirzepatide activates both GIP and GLP-1 receptors. This dual action may explain the higher average weight loss seen in trials.
GLP-1GLP-1 Receptor Activation
- •Reduces appetite and food intake
- •Slows gastric emptying (keeps you fuller longer)
- •Increases insulin secretion when blood sugar rises
- •Decreases glucagon (reduces sugar production by liver)
GIPGIP Receptor Activation
- •Enhances insulin secretion (complements GLP-1 effect)
- •May increase energy expenditure and fat breakdown
- •Affects fat storage in adipose tissue
- •The mechanism isn't fully understood yet
Why Dual Activation Matters
GIP was initially thought to promote weight gain, making tirzepatide's success surprising. Current research suggests GIP and GLP-1 work synergistically—the combination produces greater effects than either alone. The exact mechanism is still being studied, but trial results speak for themselves.
Clinical Trial Results
The SURMOUNT trial program tested tirzepatide for weight management. The results showed significantly higher weight loss than any GLP-1 medication tested previously.
SURMOUNT-1: Weight Loss in Adults
New England Journal of Medicine, 2022
Adults without diabetes, average BMI 38. At 15mg dose, 91% lost at least 5% body weight, 69% lost at least 15%, and 50% lost at least 20%. Highest weight loss ever seen in a non-surgical obesity trial.
SURMOUNT-2: Adults with Type 2 Diabetes
The Lancet, 2023
Adults with type 2 diabetes, average BMI 36. Weight loss slightly lower than SURMOUNT-1 (similar to pattern seen with semaglutide), but still substantially higher than other diabetes medications. Significant improvement in glycemic control.
SURMOUNT-4: Direct Comparison to Semaglutide 1mg
Presented at American Diabetes Association 2023
Note: This compared tirzepatide 15mg to semaglutide 1mg (Ozempic dose), not the 2.4mg Wegovy dose. Still, tirzepatide showed roughly double the weight loss in this head-to-head trial.
Dosing Protocol
Like semaglutide, tirzepatide requires gradual dose escalation. Here's the standard titration schedule for Zepbound (weight management):
Weeks 1-4: 2.5mg
Starting dose to assess tolerance. Higher than semaglutide starting dose.
Weeks 5-8: 5mg
First increase. Many people notice appetite suppression at this dose.
Weeks 9-12: 7.5mg
Mid-range therapeutic dose. Some patients stay here as maintenance.
Weeks 13-16: 10mg
Higher therapeutic dose. Used in SURMOUNT trials with significant results.
Week 17-20: 12.5mg (Optional)
Intermediate step before maximum dose. Not everyone needs this step.
Week 21+: 15mg
Maximum dose. Showed 20.9% average weight loss in SURMOUNT-1 trial.
Note: Titration can be slowed or paused if you experience significant side effects. Not everyone needs to reach 15mg—your doctor will find the dose that balances efficacy with tolerability for you.
Side Effects
Side effect profile similar to semaglutide (both are GLP-1 agonists), with gastrointestinal effects being most common. SURMOUNT-1 data:
Most Common (SURMOUNT-1)
Note: Slightly lower rates than semaglutide in some categories, possibly due to different titration schedule or dual mechanism effects.
Serious (Rare but Important)
Pancreatitis
Inflammation of pancreas. Discontinue if severe persistent abdominal pain occurs.
Gallbladder problems
Rapid weight loss increases gallstone risk. Monitor for right upper abdominal pain.
Hypoglycemia
Low blood sugar risk increases if used with insulin or sulfonylureas in diabetic patients. Monitor glucose levels.
Thyroid tumors
Boxed warning based on rodent studies (not confirmed in humans). Avoid if family history of medullary thyroid carcinoma or MEN 2.
Discontinuation Rates
In SURMOUNT-1, about 6% of participants stopped tirzepatide due to side effects, compared to 2% in the placebo group. Most discontinuations occurred early during dose escalation. Side effects typically improve over time as your body adapts.
Bottom line: Most people tolerate tirzepatide, but gastrointestinal side effects are common initially. Slow titration and dietary adjustments help.
Cost & Access
Brand-Name (Zepbound/Mounjaro)
Eli Lilly manufactures both formulations. Mounjaro approved for diabetes, Zepbound for weight management. Pricing varies by dose level.
Compounded Tirzepatide
Prepared by compounding pharmacies when brand-name supplies are limited. Same active ingredient, not FDA-approved like manufactured drugs.
Tirzepatide vs Semaglutide: Quick Comparison
| Feature | Tirzepatide | Semaglutide |
|---|---|---|
| Mechanism | Dual GIP/GLP-1 agonist | GLP-1 agonist only |
| Avg Weight Loss | 20.9% (SURMOUNT-1, 15mg) | 14.9% (STEP 1, 2.4mg) |
| Maximum Dose | 15mg weekly | 2.4mg weekly |
| Titration Time | ~20 weeks to max | ~16 weeks to max |
| Nausea Rate | 31% (SURMOUNT-1) | 44% (STEP 1) |
| Brand Names | Mounjaro, Zepbound | Ozempic, Wegovy |
| Manufacturer | Eli Lilly | Novo Nordisk |
| List Price | ~$1,000/month | ~$1,300/month |
Which One to Choose?
Tirzepatide shows higher average weight loss in trials, but semaglutide has been available longer with more real-world data. Both work well. The choice often comes down to insurance coverage, availability, cost, and individual tolerance. Your doctor can help determine which makes sense for your situation.
Compare All GLP-1 Medications
See how tirzepatide, semaglutide, liraglutide, and dulaglutide stack up on efficacy, costs, dosing, and side effects.
Medical Disclaimer
This information is for educational purposes only and does not constitute medical advice. Tirzepatide is a prescription medication that requires physician supervision. We are not healthcare providers and cannot recommend whether this medication is appropriate for you.
Clinical trial data presented here is drawn from published research including the SURMOUNT trial program. Individual results vary significantly. Talk to your doctor about potential risks, benefits, and alternatives specific to your health situation.