Tirzepatide is a once-weekly injectable medication that activates both GLP-1 and GIP receptors. It was first approved under the brand name Mounjaro in May 2022 for adults with type 2 diabetes to improve blood sugar control. In November 2023 the same molecule received a separate FDA approval under the brand name Zepbound specifically for chronic weight management in adults with obesity or overweight plus at least one weight-related condition.
The distinction between Mounjaro and Zepbound is primarily the approved indication, not the drug itself. Both products contain identical tirzepatide in the same pen devices and dose strengths. The dual approval allows physicians to prescribe the medication for either diabetes or weight loss depending on the patient’s primary diagnosis and medical needs.
This article explains the current FDA-approved status of tirzepatide for weight loss, the clinical evidence that supported the approval, differences in how it is prescribed for diabetes versus obesity, and key considerations for patients and providers. The information reflects the regulatory landscape as of 2025.
Understanding Tirzepatide Approvals
The FDA approves medications for specific uses based on clinical trial data showing safety and efficacy for that indication. Mounjaro was studied in the SURPASS program, which enrolled people with type 2 diabetes. Those trials demonstrated significant A1C reductions and weight loss as secondary outcomes.
Zepbound was evaluated in the SURMOUNT program, which enrolled adults with obesity or overweight plus comorbidities but without diabetes. These studies focused primarily on weight loss as the main endpoint, with blood pressure, lipids, and quality-of-life measures as secondary outcomes. The data showed larger average weight reductions than seen with single GLP-1 agonists.
Because the active ingredient, dosing, and delivery device are the same, many clinicians prescribe Mounjaro off-label for weight loss when Zepbound is not covered or available. Off-label use is legal and common but may affect insurance reimbursement.
FDA-Approved Indications and Labeling
Mounjaro is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Weight loss is listed as a common side effect but not as a primary indication.
Zepbound is indicated for chronic weight management in adults with an initial BMI of 30 kg/m² or greater (obesity) or 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbid condition (hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, or cardiovascular disease). It must be used in addition to reduced-calorie diet and increased physical activity.
The two labels have different safety warnings, dosing instructions, and patient counseling sections tailored to the approved population. Both carry the same boxed warning about possible thyroid C-cell tumors based on rodent studies.
Clinical Evidence Supporting Weight-Loss Approval
The SURMOUNT-1 trial enrolled 2,539 adults with obesity or overweight (BMI ≥30 or ≥27 with comorbidity) but without diabetes. Participants received tirzepatide 5 mg, 10 mg, 15 mg, or placebo for 72 weeks. The 15 mg group lost an average of 20.9% body weight compared with 3.1% on placebo.
SURMOUNT-2 studied 938 adults with type 2 diabetes and obesity/overweight. Tirzepatide 10 mg and 15 mg produced 13.4% and 15.7% average weight loss versus 3.2% with placebo. A1C reductions were also superior.
SURMOUNT-3 and SURMOUNT-4 added intensive lifestyle intervention or withdrawal/maintenance phases. Both confirmed that continued treatment sustains loss, while discontinuation leads to substantial regain. These results supported the chronic weight-management indication.
Comparison of Tirzepatide vs Other Weight-Loss Medications
| Medication | Active Ingredient | Primary Mechanism | Average Weight Loss (1 year) |
|---|---|---|---|
| Zepbound | Tirzepatide | Dual GLP-1 + GIP agonist | 15–22% |
| Wegovy | Semaglutide | GLP-1 agonist | 12–17% |
| Saxenda | Liraglutide | GLP-1 agonist | 5–10% |
| Xenical | Orlistat | Lipase inhibitor | 5–10% |
| Phentermine/topiramate (Qsymia) | Combination | Appetite suppressant | 8–10% |
Tirzepatide currently shows the highest average weight loss among FDA-approved medications in long-term trials.
Side Effects and Safety Considerations
The most common side effects are gastrointestinal: nausea, diarrhea, vomiting, constipation, abdominal pain, and decreased appetite. These are dose-dependent and occur most often during escalation. Nausea affects 25–40% of patients at higher doses but usually improves after 4–8 weeks.
Rare but serious risks include pancreatitis, gallbladder-related events (cholelithiasis, cholecystitis), acute kidney injury (usually linked to dehydration), and hypersensitivity reactions. The prescribing label includes a boxed warning about possible thyroid C-cell tumors based on rodent studies; human relevance remains unclear.
Patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 should not use tirzepatide. Gastroparesis, severe gastrointestinal disease, or history of pancreatitis are also contraindications or require caution.
Dosing and Administration for Weight Loss
Zepbound follows a gradual titration schedule to improve tolerability:
- Weeks 1–4: 2.5 mg once weekly
- Weeks 5–8: 5 mg once weekly
- Weeks 9–12: 7.5 mg once weekly
- Weeks 13–16: 10 mg once weekly
- Weeks 17+: 12.5 mg or 15 mg once weekly (maximum dose)
Injections are subcutaneous in the abdomen, thigh, or upper arm. Patients rotate sites weekly to reduce irritation. The pen is single-use and should be stored refrigerated until first use, then at room temperature or refrigerated for up to 30 days.
Missed doses should be taken within 4 days if possible; otherwise, skip and resume the regular schedule. Never take two doses within 3 days of each other.
Lifestyle Support for Optimal Results
Tirzepatide works best when paired with a reduced-calorie diet and increased physical activity. Aim for a 500–750 kcal daily deficit through portion control and nutrient-dense foods. Protein intake of 1.6–2.2 g/kg ideal body weight helps preserve lean mass.
Strength training 2–3 times per week prevents excessive muscle loss. Aerobic activity (150 minutes moderate intensity weekly) supports cardiovascular health and fat oxidation. Sleep 7–9 hours nightly; poor sleep raises hunger hormones and reduces satiety signals.
Stress management reduces cortisol-driven cravings. Simple practices like deep breathing or short walks help maintain adherence.
Insurance Coverage and Access Considerations
Zepbound is covered by many commercial plans for weight management when criteria are met (BMI ≥30 or ≥27 with comorbidity). Prior authorization is common and may require documentation of previous weight-loss attempts. Medicare Part D excludes coverage for obesity drugs alone.
Manufacturer savings cards reduce copays to as low as $25–$50 per month for commercially insured patients (subject to annual caps). Patient assistance programs provide free medication to qualifying low-income uninsured individuals. Patient advocacy groups can assist with appeals if coverage is denied.
When to Consult Your Healthcare Provider
Contact your prescriber if side effects interfere with daily life, eating becomes too difficult, or weight loss is slower than expected after reaching higher doses. They can adjust titration speed, manage symptoms, or evaluate underlying conditions.
Seek immediate care for severe abdominal pain, persistent vomiting, signs of dehydration, or allergic reactions. Report any neck lumps or swallowing difficulty, which require thyroid evaluation.
Regular follow-up visits monitor A1C (if diabetic), blood pressure, lipids, and body composition. These appointments also allow discussion of maintenance dosing or long-term plans.
Tirzepatide is FDA-approved for chronic weight management under the brand Zepbound when specific BMI and comorbidity criteria are met. The approval is supported by large trials showing 15–22% average body weight reduction over 72 weeks at higher doses. It offers one of the most potent non-surgical options available, but like all medications it requires medical supervision and lifestyle support for safe, sustained results.
FAQ
Is Zepbound the same medication as Mounjaro?
Yes. Both contain identical tirzepatide in the same pens and doses. The only difference is the FDA-approved indication: Mounjaro for type 2 diabetes and Zepbound for chronic weight management.
What BMI do I need to qualify for Zepbound?
Zepbound is approved for adults with BMI ≥30 kg/m² (obesity) or BMI ≥27 kg/m² (overweight) with at least one weight-related condition such as hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, or cardiovascular disease.
How much weight can I expect to lose on Zepbound?
Average loss in trials was 15–22% of starting body weight at the 10 mg and 15 mg doses over 72 weeks. Individual results vary based on adherence, starting weight, diet, and activity level.
Is tirzepatide approved for weight loss in people without diabetes?
Yes. Zepbound is specifically approved for chronic weight management regardless of diabetes status, provided BMI and comorbidity criteria are met. Mounjaro is approved only for type 2 diabetes.
Can my doctor prescribe Mounjaro off-label for weight loss?
Yes, physicians may prescribe Mounjaro off-label for weight loss when clinically appropriate. Insurance coverage for off-label use is often denied, so patients may pay full cash price or use manufacturer assistance programs.
What should I do if my insurance denies coverage for Zepbound?
Appeal the denial with medical documentation of BMI, comorbidities, and previous weight-loss attempts. Ask your doctor to submit a prior authorization or letter of medical necessity. Manufacturer copay cards or patient assistance programs can help bridge the gap.
Dr. Usman is a medical content reviewer with 12+ years of experience in healthcare research and patient education. He specializes in evidence-based health information, medications, and chronic health topics. His work is based on trusted medical sources and current clinical guidelines to ensure accuracy, transparency, and reliability. Content reviewed by Dr. Usman is for educational purposes and does not replace professional medical advice.