Tirzepatide Dosing Guide

Tirzepatide Dosing Calculator

Use this calculator to determine your current dose and track your titration schedule based on FDA-approved protocols:

FDA-Approved Dosing Protocols

Tirzepatide is available under two brand names with different approved indications and dosing schedules. Mounjaro is approved for type 2 diabetes, while Zepbound is approved for chronic weight management. Both use the same active ingredient but follow distinct titration protocols optimized for their respective indications.

Mounjaro (Type 2 Diabetes)

Standard Titration Schedule

The FDA-approved dosing for type 2 diabetes follows a gradual escalation protocol designed to minimize gastrointestinal side effects while achieving glycemic control. The starting dose is significantly lower than the maintenance dose, with increases occurring every 4 weeks based on tolerability and glycemic response.

Dose Selection Considerations

The optimal maintenance dose varies by individual. In the SURPASS clinical trials, the 5 mg dose produced substantial HbA1c reductions (1.9% average decrease) and was sufficient for many patients to reach their glycemic targets. The 10 mg dose provided additional benefit (2.1% HbA1c reduction) with acceptable tolerability in most patients. The 15 mg dose offered maximal efficacy (2.3% HbA1c reduction) but with higher rates of gastrointestinal side effects.

Healthcare providers typically escalate to higher doses only if:

• HbA1c remains above target on current dose
• Patient tolerates current dose without significant side effects
• Additional weight loss is desired (higher doses produce greater weight reduction)
• Patient has been on current dose for at least 4 weeks

Maintenance Dosing

Once an effective dose is reached, patients continue that dose indefinitely. In clinical trials, most patients remained on their maintenance dose for years without need for further escalation. However, dose adjustments may be necessary if:

• Glycemic control deteriorates (HbA1c rises above target)
• Significant weight changes occur
• Other diabetes medications are added or removed
• Side effects become intolerable (may require dose reduction)
• Kidney function declines (though no dose adjustment is required for mild-moderate impairment)

Zepbound (Chronic Weight Management)

Weight Loss Titration Schedule

The FDA-approved dosing for weight management follows a similar escalation pattern but with a different target dose range. The SURMOUNT clinical trials established that higher doses produce greater weight loss, with the 10 mg and 15 mg doses showing superior efficacy.

Target Maintenance Dose

For weight management, the 10 mg and 15 mg doses are considered optimal. In the SURMOUNT-1 trial, participants on 10 mg lost an average of 19.5% of body weight, while those on 15 mg lost 20.9%. The 5 mg dose, while effective for diabetes, produced less weight loss (15.0%) and is generally not recommended as a maintenance dose for weight management unless higher doses are not tolerated.

Dose Optimization Strategy

The recommended approach for weight management is to escalate to the highest tolerated dose, typically 10 mg or 15 mg. Patients should remain on each dose for at least 4 weeks before escalating to assess both efficacy and tolerability. If significant nausea or other gastrointestinal side effects occur, the escalation can be slowed or the patient can remain on the current dose longer before advancing.

Administration Technique

Injection Sites

Tirzepatide is administered as a subcutaneous injection in the abdomen, thigh, or upper arm. The abdomen (except within 2 inches of the navel) is the most common injection site and may have slightly faster absorption. Patients should rotate injection sites weekly to prevent lipohypertrophy (fatty lumps under the skin) or lipoatrophy (loss of fat tissue).

Injection Timing

Tirzepatide can be administered at any time of day, with or without meals. The key is consistency - patients should inject on the same day each week. If a dose is missed, it should be administered as soon as possible within 4 days (96 hours) of the missed dose. If more than 4 days have passed, skip the missed dose and resume the regular schedule.

Pre-filled Pen Instructions

Mounjaro and Zepbound come in single-dose pre-filled pens that require no reconstitution:

1. Remove pen from refrigerator 30 minutes before injection to allow it to reach room temperature
2. Check the medication - it should be clear and colorless to slightly yellow
3. Wash hands thoroughly with soap and water
4. Clean injection site with alcohol swab and let dry
5. Remove pen cap and place pen perpendicular to skin
6. Press pen firmly against skin until you hear the first click
7. Keep pressing - you'll hear a second click after about 5-10 seconds
8. Count to 10 before removing pen from skin
9. Dispose of pen in sharps container (do not reuse)

Storage Requirements

Unopened tirzepatide pens must be stored in the refrigerator at 36-46°F (2-8°C). Do not freeze. Once removed from the refrigerator, pens can be kept at room temperature (up to 86°F/30°C) for up to 21 days. Protect from light by keeping in the original carton until use. Never use a pen that has been frozen, even if it has thawed.

Missed Dose Protocol

Within 4 Days of Scheduled Dose

If you remember within 4 days (96 hours) of your scheduled injection day, administer the dose as soon as possible. Then resume your regular weekly schedule. For example, if your regular day is Monday and you remember on Thursday, inject on Thursday and then return to Monday injections.

More Than 4 Days Late

If more than 4 days have passed since your scheduled dose, skip that dose entirely and wait until your next regularly scheduled day. Do not double the dose to make up for the missed injection. Taking two doses close together significantly increases the risk of severe nausea, vomiting, and other gastrointestinal side effects.

Changing Injection Day

If you need to permanently change your injection day, you can do so as long as the last dose was administered at least 3 days (72 hours) earlier. For example, if you inject on Mondays but want to switch to Fridays, you can inject on Friday as long as it's been at least 3 days since Monday. Once you inject on the new day, continue that schedule weekly.

Dose Adjustments for Special Populations

Renal Impairment

No dose adjustment is required for patients with mild, moderate, or severe renal impairment, including those with end-stage renal disease. Tirzepatide is eliminated primarily through protein catabolism rather than renal excretion. However, patients with severe renal impairment may experience more gastrointestinal side effects and should be monitored closely during dose escalation.

Hepatic Impairment

No dose adjustment is required for patients with hepatic impairment. Clinical studies included patients with mild to moderate hepatic impairment without safety concerns. However, tirzepatide has not been studied in patients with severe hepatic impairment, so use caution in this population.

Elderly Patients

No dose adjustment is required based on age alone. However, elderly patients may be more susceptible to gastrointestinal side effects and dehydration. A slower titration schedule (remaining on each dose for 6-8 weeks instead of 4 weeks) may improve tolerability in patients over 65 years old.

Pediatric Use

Tirzepatide is not approved for use in patients under 18 years of age. Safety and efficacy have not been established in pediatric populations. Clinical trials in adolescents are ongoing but results are not yet available.

Drug Interactions Affecting Dosing

Insulin and Insulin Secretagogues

When tirzepatide is added to insulin or sulfonylurea therapy, the dose of insulin or sulfonylurea should be reduced to minimize hypoglycemia risk. In clinical trials, insulin doses were typically reduced by 20-30% when initiating tirzepatide. Sulfonylureas were often discontinued entirely or reduced to the lowest available dose. Close glucose monitoring is essential during the first 4-8 weeks of combination therapy.

Oral Medications

Tirzepatide delays gastric emptying, which can affect the absorption of oral medications. For medications where timing is critical (such as oral contraceptives, levothyroxine, or antibiotics), consider taking them at least 1 hour before or 4 hours after tirzepatide injection. However, since tirzepatide is injected weekly, this interaction is less clinically significant than with daily GLP-1 agonists.

Warfarin

Tirzepatide may affect warfarin absorption and metabolism. Patients on warfarin should have their INR monitored more frequently when starting tirzepatide and after dose changes. Warfarin dose adjustments may be necessary.

Overdose Information

Can Tirzepatide Overdose Be Fatal?

There are no reported cases of fatal tirzepatide overdose in clinical trials or post-marketing surveillance. Unlike insulin, tirzepatide does not cause severe hypoglycemia that could be life-threatening. However, significant overdose can cause severe and prolonged gastrointestinal symptoms that may lead to serious complications if not properly managed.

Overdose Symptoms

Symptoms of tirzepatide overdose are primarily gastrointestinal and may include:

• Severe nausea and vomiting - May persist for several days due to tirzepatide's long half-life
• Severe diarrhea - Can lead to dehydration and electrolyte imbalances
• Abdominal pain - May be severe and cramping in nature
• Dehydration - From fluid losses through vomiting and diarrhea
• Hypoglycemia - More likely if patient is also taking insulin or sulfonylureas
• Acute pancreatitis - Rare but serious complication of overdose
• Acute kidney injury - Secondary to severe dehydration

Overdose Management

There is no specific antidote for tirzepatide overdose. Management is supportive and symptomatic:

1. Discontinue tirzepatide immediately - Do not administer the next scheduled dose
2. Monitor vital signs and hydration status - Check blood pressure, heart rate, and signs of dehydration
3. Provide aggressive hydration - IV fluids may be necessary for severe vomiting or diarrhea
4. Monitor blood glucose - Check every 2-4 hours, especially if patient is on other diabetes medications
5. Antiemetic medications - Ondansetron or promethazine for severe nausea
6. Monitor for pancreatitis - Check lipase levels if severe abdominal pain develops
7. Monitor kidney function - Check creatinine and electrolytes if dehydration is severe

Recovery Timeline

Due to tirzepatide's 5-day half-life, overdose symptoms may persist for 1-2 weeks. The medication cannot be removed by dialysis. Symptoms typically peak within 24-48 hours of overdose and gradually improve over 5-10 days. Patients should not resume tirzepatide until symptoms have completely resolved and should restart at a lower dose than the overdose amount.

Preventing Accidental Overdose

Accidental overdose is rare with pre-filled pens but can occur if:

• Patient injects twice in one week (forgetting they already injected)
• Patient uses a higher-dose pen than prescribed
• Patient injects two pens thinking one is insufficient
• Compounded tirzepatide is incorrectly reconstituted or measured

To prevent overdose, patients should mark their calendar after each injection and keep used pens until the next injection day as a reminder.

Monitoring Requirements

Baseline Assessment

Before starting tirzepatide, patients should have:

• HbA1c measurement (for diabetes indication)
• Fasting lipid panel
• Comprehensive metabolic panel (kidney and liver function)
• Baseline weight and BMI
• Blood pressure measurement
• Personal and family history of medullary thyroid carcinoma or MEN 2
• History of pancreatitis
• Diabetic retinopathy screening (for diabetes patients)

Ongoing Monitoring

During tirzepatide therapy, regular monitoring should include:

• HbA1c - Every 3 months until stable, then every 6 months
• Weight - Monthly during titration, then every 3 months
• Blood pressure - At each visit (may decrease with weight loss)
• Kidney function - Every 6-12 months, more frequently if impaired
• Lipid panel - Every 6-12 months (typically improves with weight loss)
• Signs of pancreatitis - Educate patients to report severe abdominal pain
• Diabetic retinopathy - Annual eye exams for diabetes patients
• Gallbladder disease - Educate patients about symptoms of gallstones

When to Discontinue

Consider discontinuing tirzepatide if:

• Acute pancreatitis develops
• Severe, persistent gastrointestinal side effects occur
• Acute kidney injury develops
• Severe allergic reaction occurs
• Patient becomes pregnant (discontinue immediately)
• Diabetic retinopathy worsens rapidly
• Patient develops medullary thyroid carcinoma
• Inadequate response after 6 months at maximum tolerated dose

Cost Considerations

Brand Name Pricing

Tirzepatide is expensive, with list prices around $1,000-1,400 per month depending on the dose. Mounjaro and Zepbound have identical pricing despite different indications. Higher doses cost more due to the larger amount of active ingredient per pen.

Insurance Coverage

Insurance coverage varies significantly:

• Mounjaro (diabetes) - Generally well-covered by insurance with prior authorization. Copays typically $25-100/month with commercial insurance.
• Zepbound (weight loss) - Coverage is less consistent. Many plans exclude weight loss medications entirely. Medicare does not cover weight loss medications.
• Prior authorization - Usually required, documenting BMI ≥30 (or ≥27 with comorbidities) and previous weight loss attempts.

Manufacturer Savings Programs

Eli Lilly offers savings cards that can reduce out-of-pocket costs to $25-$550 per month for commercially insured patients. These programs have eligibility requirements and may not be available with government insurance (Medicare, Medicaid).

Compounded Tirzepatide

Due to high costs and shortages, compounded tirzepatide has become available at $200-400/month. However, compounded versions are not FDA-approved, may have quality and potency variations, and lack the safety oversight of brand-name products. The FDA has issued warnings about compounded GLP-1 agonists.