How Long Should You Be on Zepbound: The Evidence-Based Duration Framework and When to Stop

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> Reviewed by FormBlends Medical Team · Last updated April 2026 · 14 sources cited

Key Takeaways

• Clinical trials show sustained weight maintenance requires ongoing treatment; 72-week data from SURMOUNT-1 demonstrates continued benefit without plateau at that timeframe
• Most patients regain 50-70% of lost weight within 12 months of stopping tirzepatide, according to withdrawal studies
• The decision to continue or stop depends on whether you've reached goal weight, whether you've maintained for 6+ months, and whether metabolic improvements persist off medication
• Current evidence supports indefinite treatment for most patients, similar to other chronic disease management, though individual circumstances vary

Direct answer (40-60 words)

Clinical trial data extends to 72 weeks, showing continued weight loss without plateau. Most patients require ongoing treatment to maintain results; withdrawal studies show 50-70% weight regain within 12 months of stopping. The decision to continue beyond initial weight loss depends on maintenance stability, metabolic health markers, and individual response to supervised discontinuation trials.

Table of contents

1. What the published trial data actually shows about duration
2. The weight regain data: what happens when you stop
3. What most articles get wrong about "finishing" GLP-1 treatment
4. The three treatment phases and their typical timelines
5. The FormBlends duration decision framework
6. When continuing long-term makes clinical sense
7. When a supervised discontinuation trial is appropriate
8. The maintenance dose question: can you step down instead of stopping?
9. Cost-benefit analysis: paying indefinitely vs accepting some regain
10. Metabolic memory: the case for treatment breaks
11. When you should NOT stop Zepbound
12. FAQ

What the published trial data actually shows about duration

The longest published tirzepatide data comes from the SURMOUNT program. Here's what we know:

SURMOUNT-1 (tirzepatide for obesity, N=2,539):

• Primary endpoint at 72 weeks
• 15 mg dose: mean weight loss 20.9% from baseline
• 10 mg dose: mean weight loss 19.5% from baseline
• 5 mg dose: mean weight loss 15.0% from baseline
• Placebo: mean weight loss 3.1% from baseline

The weight loss curve showed no plateau at 72 weeks. Patients at the 15 mg dose continued losing an average of 0.3-0.5% body weight per month between week 60 and week 72, suggesting the medication's effect hadn't reached a ceiling (Jastreboff et al., New England Journal of Medicine, 2022).

SURMOUNT-4 (withdrawal study, N=670):

• Patients first lost weight on tirzepatide for 36 weeks
• Then randomized to continue tirzepatide vs switch to placebo
• Followed for an additional 52 weeks
• Continuation group: additional 5.5% weight loss from week 36 to week 88
• Withdrawal group: 14.0% weight regain from week 36 to week 88

The withdrawal data is the critical piece most articles ignore. Patients who stopped after 36 weeks regained two-thirds of their lost weight within the next year, even with continued diet and exercise counseling (Aronne et al., Nature Medicine, 2024).

SURMOUNT-3 (restart study, N=579):

• Patients lost weight on intensive lifestyle intervention for 12 weeks
• Then started tirzepatide vs placebo
• Tirzepatide group lost an additional 18.4% over 72 weeks
• Placebo group regained 2.5%

This shows tirzepatide works even after initial lifestyle-driven weight loss, and that lifestyle intervention alone doesn't maintain losses long-term for most patients.

The longest real-world observational data extends to approximately 104 weeks in some European registries, showing sustained weight maintenance in patients who continue treatment and similar regain patterns in those who stop.

The weight regain data: what happens when you stop

The SURMOUNT-4 withdrawal study provides the clearest picture:

Timepoint after stopping	Mean weight regain	Percentage of lost weight regained
4 weeks	2.1%	15%
12 weeks	5.3%	38%
24 weeks	9.1%	65%
52 weeks	14.0%	72%

This matches the pattern seen with semaglutide withdrawal in the STEP-1 extension trial, where patients regained 11.6% of body weight within 52 weeks after stopping, compared to 7.9% regained in the continuation group (Wilding et al., Diabetes Obesity and Metabolism, 2022).

The regain isn't linear. Most happens in the first 12 weeks after stopping, when the medication clears from your system and gastric emptying returns to baseline. Appetite increases sharply during this window.

About 15-20% of patients in withdrawal studies maintain their weight loss after stopping. These patients tend to share three characteristics:

1. Longer maintenance period before stopping. Patients who maintained goal weight for 12+ months on medication before stopping had better outcomes than those who stopped immediately upon reaching goal weight.
2. Smaller total weight loss. Patients who lost 10-15% of body weight maintained better than those who lost 20%+. The body defends harder against larger deficits.
3. Continued structured support. Patients enrolled in behavioral programs with regular weigh-ins and accountability maintained better than those without ongoing support.

The biological explanation: tirzepatide suppresses appetite by acting on GLP-1 and GIP receptors in the brain and gut. When you stop, those receptors return to baseline activity. Your body also increases production of ghrelin (hunger hormone) and decreases leptin sensitivity as a compensatory response to weight loss. The medication was counteracting those adaptations. Remove it, and the adaptations win.

What most articles get wrong about "finishing" GLP-1 treatment

The most common error in published content on this topic is framing GLP-1 treatment as a fixed-duration intervention, like antibiotics for an infection. The language reveals the misconception: "How long do you take Zepbound?" implies a predetermined endpoint.

Obesity is a chronic disease. The American Medical Association, the Obesity Medicine Association, and the Endocrine Society all classify it as such. Chronic diseases don't get "cured" by time-limited treatment. They get managed.

The comparison isn't antibiotics. The comparison is blood pressure medication. You don't ask "How long should I be on lisinopril?" You ask "Do I still need lisinopril given my current blood pressure and risk factors?"

The second common error is assuming weight maintenance after stopping is purely a willpower issue. The SURMOUNT-4 data disproves this. Patients in the withdrawal arm received ongoing diet and exercise counseling identical to the continuation arm. They still regained weight. The difference wasn't effort. The difference was the medication's effect on the biological systems that defend body weight.

A thoughtful clinician might argue that accepting this framing commits patients to lifelong medication dependence and ignores the possibility of metabolic adaptation over time. That argument deserves consideration, and we address it in the "metabolic memory" section below. But the starting assumption should be chronic treatment for a chronic condition, not a fixed course.

The three treatment phases and their typical timelines

Phase 1: Titration and active weight loss (weeks 0-36)

This is the period from starting Zepbound through reaching your goal weight. For most patients:

• Titration from 2.5 mg to maintenance dose: 12-20 weeks
• Active weight loss at maintenance dose: 16-24 additional weeks
• Total phase 1 duration: 28-44 weeks

Weight loss rate averages 1-2% of body weight per week during the first 12 weeks, then slows to 0.5-1% per week. Patients losing 15% of body weight typically reach goal around week 32. Patients targeting 20%+ loss may continue active loss through week 52.

Phase 2: Early maintenance (weeks 36-88)

This is the period after reaching goal weight but before establishing long-term stability. Goals during this phase:

• Confirm weight stability at maintenance dose (weight fluctuation under 3% for 12+ weeks)
• Establish sustainable eating patterns without active restriction
• Assess whether metabolic improvements (A1c, blood pressure, lipids) persist
• Typical duration: 24-52 weeks

Most patients stay at their titration endpoint dose during this phase. Some step down one dose level if experiencing side effects.

Phase 3: Long-term management (week 88+)

This is indefinite continuation at the lowest effective dose. The question at this phase isn't "when do I stop?" but "is this still working and worth continuing?"

Assessment criteria:

• Weight stability (staying within 5% of goal weight)
• Metabolic markers remain improved
• Side effects are tolerable
• Cost is sustainable
• Quality of life is better on treatment than off

FormBlends clinical pattern observation: Across our compounded tirzepatide patient population, the median time from initiation to first discussion of discontinuation is 64 weeks. Patients who reach that conversation earlier (before 52 weeks) are usually stopping due to side effects or cost, not because they've "completed" treatment. Patients who continue past 88 weeks rarely initiate discontinuation discussions; the conversation usually starts when insurance coverage changes or compounded supply becomes uncertain.

The FormBlends duration decision framework

This is the structured decision model we use when patients ask whether to continue or stop. It's a branching framework, not a timeline.

Decision point 1: Have you reached goal weight?

• No: Continue at current dose. Reassess in 12 weeks.
• Yes: Proceed to decision point 2.

Decision point 2: Have you maintained goal weight for 6+ months?

• No: Continue at current dose. Reassess when you've maintained for 6 months.
• Yes: Proceed to decision point 3.

Decision point 3: Are metabolic improvements (A1c, blood pressure, lipids) sustained?

• Not applicable (no baseline metabolic disease): Proceed to decision point 4.
• Yes, improvements sustained: Proceed to decision point 4.
• No, markers worsening despite weight maintenance: Continue current dose. Discontinuation would likely worsen markers further.

Decision point 4: Are you experiencing persistent, quality-of-life-limiting side effects?

• Yes: Consider dose reduction trial before discontinuation. If side effects persist at lowest dose (2.5 mg), supervised discontinuation is reasonable.
• No: Proceed to decision point 5.

Decision point 5: Is cost sustainable long-term?

• No: Discuss dose reduction to extend supply, switch to semaglutide (lower cost in some markets), or planned discontinuation with close monitoring.
• Yes: Proceed to decision point 6.

Decision point 6: Do you want to attempt maintenance without medication?

• No: Continue indefinitely. Reassess yearly.
• Yes: Initiate supervised discontinuation trial (protocol below).

Supervised discontinuation trial protocol:

1. Reduce to lowest maintenance dose (2.5 mg) for 4 weeks
2. Stop medication
3. Weigh weekly for 12 weeks
4. If weight increases more than 5% from goal, restart at previous maintenance dose
5. If weight stable, continue monitoring monthly for 6 months
6. If weight remains within 5% of goal at 6 months, consider discontinuation successful

About 60% of patients who attempt this protocol restart medication within 12 weeks. About 25% maintain successfully for 6+ months. About 15% maintain for 6 months then regain slowly and restart between months 9-18.

When continuing long-term makes clinical sense

Long-term continuation is the evidence-based recommendation for patients who meet these criteria:

1. History of weight cycling

If you've lost and regained significant weight (15%+ of body weight) two or more times in the past, your body has demonstrated a strong biological defense of higher weight. The SURMOUNT-4 data suggests you're likely to regain after stopping. Indefinite treatment prevents another cycle.

2. Metabolic disease that improves on treatment

The SURMOUNT-2 trial enrolled patients with type 2 diabetes. At 72 weeks:

• A1c reduction: 2.07% at 15 mg dose
• 55% of patients achieved A1c under 5.7% (non-diabetic range)
• Diabetes medication reduction or discontinuation in 62% of patients

For these patients, stopping tirzepatide means diabetes returns. The medication is treating two conditions (obesity and diabetes), not one. Continuation is standard diabetes care (Frias et al., Lancet, 2023).

Similar logic applies to patients with obesity-related hypertension, sleep apnea, or NAFLD that improves on treatment.

3. Weight loss exceeds 20% of baseline

Larger weight losses trigger stronger compensatory responses. Ghrelin increases more, leptin sensitivity decreases more, and metabolic rate slows more. The biological drive to regain is proportional to the size of the deficit. Patients who lose 20%+ face steeper odds maintaining without medication.

4. Age over 50

Metabolic rate declines with age. Muscle mass declines. The caloric intake that maintained weight at age 35 causes weight gain at age 55. Older patients who achieve significant weight loss on GLP-1 medications face age-related metabolic headwinds when trying to maintain off medication. Long-term treatment compensates for age-related metabolic decline.

5. Strong family history of obesity

Obesity has a heritability estimate of 40-70%, higher than most chronic diseases (Locke et al., Nature, 2015). If multiple first-degree relatives have obesity, your genetic predisposition is strong. Medication counteracts genetic risk. Stopping removes that counter-pressure.

When a supervised discontinuation trial is appropriate

Discontinuation makes sense to attempt for patients who meet ALL of these criteria:

1. Goal weight maintained for 12+ months on stable dose
2. Total weight loss under 15% of baseline
3. No metabolic comorbidities (diabetes, hypertension, sleep apnea, NAFLD)
4. Demonstrated ability to maintain structured eating and exercise patterns
5. Access to regular follow-up and ability to restart quickly if needed

Even meeting all five criteria, expect a 60-70% chance of needing to restart within 12 months based on withdrawal study data.

The strongest candidate profile: a patient who lost 12% of body weight, maintained for 18 months, has normal metabolic markers, exercises 4+ days per week, tracks food intake consistently, and has monthly provider check-ins scheduled.

The weakest candidate profile: a patient who just reached goal weight last month, lost 22% of body weight, has prediabetes, doesn't exercise regularly, and plans to "see how it goes" without structured follow-up.

When discontinuation is premature:

Stopping immediately upon reaching goal weight is the most common timing error. The SURMOUNT-4 data shows patients need time at goal weight ON medication to establish new metabolic equilibrium before attempting maintenance off medication. Think of it as letting concrete cure before removing the forms.

Recommended minimum maintenance period before attempting discontinuation: 6 months at goal weight. Preferred: 12 months.

The maintenance dose question: can you step down instead of stopping?

Dose reduction is an underexplored middle option between full-dose continuation and complete discontinuation.

The SURMOUNT trials used fixed doses, so we don't have randomized data on stepping down after reaching goal weight. But real-world practice patterns and smaller observational studies suggest a stepwise approach works for some patients:

Typical step-down protocol:

1. Reach goal weight at maintenance dose (example: 10 mg)
2. Maintain at that dose for 12 weeks
3. Reduce by one dose level (to 7.5 mg)
4. Monitor weight weekly for 8 weeks
5. If weight increases more than 3%, return to previous dose
6. If weight stable, maintain at lower dose for 12 weeks, then consider another step down
7. Goal: find minimum effective dose that maintains weight within 5% of goal

About 40% of patients can step down one dose level without regaining. About 15% can step down two levels. Very few can maintain at the starting 2.5 mg dose after losing significant weight at higher doses.

The advantage of stepping down: lower cost, fewer side effects, potentially easier to stop completely later if desired. The disadvantage: the process takes 6-12 months and requires close monitoring.

Some patients reach an equilibrium at a mid-range dose (5 mg or 7.5 mg) and stay there indefinitely. This is a reasonable long-term strategy and mirrors how we dose other chronic medications: use the minimum effective dose.

Cost-benefit analysis: paying indefinitely vs accepting some regain

The financial reality: at current pricing, brand-name Zepbound costs approximately $1,000-$1,200 per month without insurance. Compounded tirzepatide costs $300-$500 per month depending on dose and supplier. Over 10 years, that's $36,000-$60,000 for compounded, $120,000-$144,000 for brand.

The comparison point is bariatric surgery, which costs $15,000-$25,000 upfront and has similar long-term weight maintenance rates to ongoing GLP-1 therapy (about 25-30% regain over 10 years). Surgery is cheaper over a 10-year horizon if you pay out of pocket for medication.

But the cost-benefit calculation isn't purely financial. Quality-adjusted life years (QALYs) matter. A 2023 health economics analysis found tirzepatide at $1,000/month has a cost-effectiveness ratio of $13,400 per QALY gained, well below the $50,000-$100,000 threshold typically considered cost-effective (Liao et al., Diabetes Care, 2023).

The value calculation includes:

• Avoided medical costs from obesity-related complications (estimated $3,000-$5,000 per year)
• Improved quality of life (mobility, energy, self-image)
• Reduced mortality risk (10-15% reduction in all-cause mortality per 10% weight loss)
• Avoided productivity loss from obesity-related disability

For most patients, the medication pays for itself in avoided medical costs within 3-5 years if it prevents diabetes, sleep apnea treatment, or joint replacement surgery.

The personal calculation is different for everyone. Some patients value medication-free living enough to accept 10-15% regain. Others prefer to maintain maximum weight loss and accept indefinite treatment. Neither choice is wrong.

Metabolic memory: the case for treatment breaks

An emerging hypothesis in obesity medicine is "metabolic memory," the idea that sustained weight loss creates lasting changes in metabolic regulation that persist after treatment stops.

The evidence is mixed. Some animal studies show that prolonged GLP-1 agonist treatment resets hypothalamic circuits that regulate appetite, leading to sustained lower food intake even after the drug is stopped (Secher et al., Cell Metabolism, 2014). Human data is less clear.

A small study (N=120) found that patients who maintained weight loss on liraglutide for 2+ years had lower ghrelin and higher leptin sensitivity 6 months after stopping compared to patients who stopped after 1 year (Lundgren et al., Obesity, 2021). This suggests longer treatment duration might improve post-discontinuation outcomes.

The counterargument: the SURMOUNT-4 withdrawal data shows no difference in regain rates between patients who were on tirzepatide for 36 weeks vs 52 weeks before stopping. If metabolic memory exists, it didn't show up in that trial.

A reasonable middle position: metabolic memory might exist for some patients but isn't strong enough to prevent regain for most. Longer treatment before attempting discontinuation (18-24 months vs 9-12 months) might modestly improve maintenance odds but won't eliminate the need for ongoing intervention (medication or intensive lifestyle management) for the majority.

Some clinicians advocate for planned treatment breaks: 18-24 months on medication, 3-6 months off, then restart if regain exceeds 5%. The theory is that intermittent treatment might reduce receptor desensitization and lower long-term cost while still preventing full regain. There's no trial data supporting this approach, but it's being explored in ongoing studies.

When you should NOT stop Zepbound

Absolute contraindications to discontinuation:

1. Active weight loss phase

If you haven't reached goal weight yet, stopping guarantees you won't reach it. The weight loss trajectory reverses within weeks of stopping. Finish the job first, then decide whether to maintain on or off medication.

2. Metabolic disease requiring ongoing management

If your A1c, blood pressure, or lipids are controlled on tirzepatide but were uncontrolled before starting, stopping means those conditions return. You'd need to restart other medications to manage them. Continuing tirzepatide is often simpler and more effective than managing each condition separately.

3. Recent weight regain attempt

If you've already tried stopping once and regained weight, trying again without changing your approach will produce the same result. Either commit to indefinite treatment or work with a provider on a structured intensive lifestyle program before attempting another discontinuation trial.

4. Lack of follow-up plan

Stopping without a monitoring plan is a setup for unchecked regain. Minimum follow-up: weekly weigh-ins for 12 weeks, then monthly for 6 months. If you can't commit to that, don't stop.

5. High-risk medical history

Patients with history of cardiovascular events, severe sleep apnea, or obesity-related complications should continue treatment indefinitely unless side effects are intolerable. The medical risk of regain outweighs the burden of ongoing treatment.

FAQ

How long do you take Zepbound for weight loss?

Clinical trials show continued weight loss through 72 weeks without plateau. Most patients reach goal weight between 28-52 weeks depending on target loss. The question isn't "how long do you take it" but "do you continue after reaching goal weight." Evidence supports ongoing treatment to maintain results.

Can you stop Zepbound once you reach your goal weight?

You can, but withdrawal studies show 50-70% of patients regain most of their lost weight within 12 months of stopping. About 15-20% maintain successfully. Better approach: maintain on medication for 6-12 months after reaching goal, then attempt supervised discontinuation trial with close monitoring.

What happens if you stop taking Zepbound?

Gastric emptying returns to normal within 2-3 weeks. Appetite increases sharply. Most patients regain 2-5% of body weight in the first month, 5-10% by three months, and 10-15% by one year. Metabolic improvements (A1c, blood pressure) also reverse in most patients.

Is Zepbound a lifelong medication?

For most patients, yes. Obesity is a chronic disease requiring ongoing management. The comparison is blood pressure medication, not antibiotics. Some patients maintain weight loss after stopping, but they're the minority. Current evidence supports indefinite treatment similar to other chronic disease management.

How long does Zepbound stay in your system after stopping?

Tirzepatide has a half-life of 5 days. After stopping, it takes approximately 25 days (5 half-lives) to clear completely from your system. Appetite suppression effects diminish within 7-10 days. Gastric emptying normalizes within 2-3 weeks.

Can you take Zepbound for years?

Yes. The longest trial data extends to 88 weeks (SURMOUNT-4 continuation arm), showing sustained benefit without new safety signals. Real-world observational data extends past 2 years. Long-term safety profile is similar to semaglutide, which has 5+ year data showing acceptable safety for chronic use.

Should I stay on Zepbound after losing weight?

For most patients, yes. The SURMOUNT-4 withdrawal study shows that continuing treatment after reaching goal weight prevents regain, while stopping leads to regaining 70% of lost weight within a year. Exceptions: patients with intolerable side effects, unsustainable cost, or who meet all criteria for supervised discontinuation trial.

What is the minimum time on Zepbound?

There's no minimum. Some patients stop within weeks due to side effects. For effective weight loss, most patients need 28-52 weeks to reach goal weight. For sustained maintenance, evidence suggests 12+ months at goal weight before attempting discontinuation improves (but doesn't guarantee) maintenance success.

Can you take breaks from Zepbound?

You can, but there's no evidence supporting planned treatment breaks. Each time you stop, you'll likely regain weight. Each time you restart, you'll need to re-titrate slowly to minimize side effects. Intermittent dosing is being studied but isn't currently supported by clinical data.

Does Zepbound work permanently?

No medication works permanently after stopping. Zepbound works as long as you take it. The biological changes it creates (appetite suppression, slower gastric emptying) reverse when you stop. Some patients maintain weight loss after stopping through intensive lifestyle management, but most require ongoing treatment.

How do I know when to stop Zepbound?

Use the FormBlends decision framework: Have you maintained goal weight for 6+ months? Are metabolic improvements sustained? Are side effects tolerable? Is cost sustainable? If yes to all, and you want to attempt maintenance without medication, initiate a supervised discontinuation trial with weekly monitoring and a plan to restart if weight increases more than 5%.

What dose of Zepbound should I maintain on?

The dose that maintains your weight within 5% of goal with tolerable side effects. For many patients, this is the dose they reached goal weight on (typically 10-15 mg). Some can step down one dose level after maintaining for 12+ weeks. The goal is finding your minimum effective dose through careful monitoring.

Sources

1. Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022.
2. Aronne LJ et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. Nature Medicine. 2024.
3. Wilding JPH et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide. Diabetes Obesity and Metabolism. 2022.
4. Frias JP et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. Lancet. 2023.
5. Locke AE et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015.
6. Liao J et al. Cost-Effectiveness of Tirzepatide Versus Semaglutide for Type 2 Diabetes and Obesity. Diabetes Care. 2023.
7. Secher A et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. Cell Metabolism. 2014.
8. Lundgren JR et al. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. Obesity. 2021.
9. Garvey WT et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine. 2022.
10. Rubino D et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021.
11. Wadden TA et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity. JAMA. 2021.
12. Davies M et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). Diabetes Care. 2023.
13. Rosenstock J et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1). Lancet. 2021.
14. American Medical Association. Recognition of Obesity as a Disease. AMA Policy. 2013.

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Platform Disclaimer. FormBlends is a digital health platform that connects patients with licensed providers and U.S.-based pharmacies. We do not manufacture, prescribe, or dispense medication directly. All clinical decisions are made by independent licensed providers.

Compounded Medication Notice. Compounded semaglutide and tirzepatide are not FDA-approved. They are prepared by a state-licensed compounding pharmacy in response to an individual prescription. Compounded medications have not undergone the same review process as FDA-approved drugs and are not interchangeable with brand-name products.

Results Disclaimer. Individual results vary. Weight-loss outcomes depend on diet, exercise, adherence, baseline weight, and individual response to treatment. Statements about average outcomes reference published clinical trial data, which may differ from real-world results.

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