What Dose of Zepbound Is Most Effective for Weight Loss?

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

Key Takeaways

• The 10 mg and 15 mg weekly doses of Zepbound (tirzepatide) produce the greatest weight loss, averaging 20.9% and 22.5% total body weight loss respectively in the SURMOUNT-1 trial
• The 5 mg dose is a maintenance tier, not a therapeutic target, and produces approximately 15% total body weight loss
• Dose effectiveness depends on tolerability, not just milligrams, because patients who discontinue due to side effects lose less weight than those who tolerate lower doses
• Most patients reach maximum effectiveness between 10 mg and 15 mg, with minimal additional benefit at higher investigational doses

Direct answer (40-60 words)

The 10 mg and 15 mg weekly doses of Zepbound produce the greatest weight loss in clinical trials, with mean reductions of 20.9% and 22.5% of total body weight at 72 weeks. The 5 mg dose is effective but produces less weight loss (15%). Effectiveness depends on individual tolerability, not just dose magnitude.

Table of contents

1. Why dose matters more for tirzepatide than other GLP-1 medications
2. The SURMOUNT-1 dose-response data
3. What most articles get wrong about "maximum dose"
4. How to interpret the 5 mg maintenance tier
5. The tolerability ceiling and why 15 mg isn't always better than 10 mg
6. Dose effectiveness in compounded tirzepatide
7. The FormBlends Dose Optimization Framework
8. When a lower dose produces better outcomes
9. Comparative effectiveness: Zepbound doses versus semaglutide doses
10. How providers choose between 10 mg and 15 mg
11. The case against dose escalation beyond 15 mg
12. FAQ
13. Sources

Why dose matters more for tirzepatide than other GLP-1 medications

Tirzepatide exhibits a steeper dose-response curve than single-agonist GLP-1 receptor agonists. The difference between the 5 mg dose and the 15 mg dose is 7.5 percentage points of total body weight loss, a clinically meaningful gap. For comparison, the difference between semaglutide 1.0 mg and 2.4 mg is approximately 5 percentage points (Wilding et al., NEJM 2021; Davies et al., Lancet 2021).

The reason lies in tirzepatide's dual mechanism. It activates both GLP-1 receptors and glucose-dependent insulinotropic polypeptide (GIP) receptors. GIP receptor activation appears to have dose-dependent effects on adipocyte metabolism and energy expenditure that don't plateau as quickly as GLP-1 effects alone (Frias et al., NEJM 2021). This means higher tirzepatide doses continue to produce incremental weight loss past the point where higher semaglutide doses show diminishing returns.

The practical implication: if you tolerate tirzepatide well at 5 mg, escalating to 10 mg or 15 mg will likely produce substantially more weight loss. If you tolerate semaglutide well at 1.0 mg, escalating to 2.4 mg produces a smaller incremental benefit.

The SURMOUNT-1 dose-response data

The SURMOUNT-1 trial (Jastreboff et al., NEJM 2022) enrolled 2,539 adults with obesity (BMI 30 or greater) or overweight (BMI 27 or greater) with at least one weight-related comorbidity, excluding diabetes. Participants were randomized to placebo or tirzepatide at 5 mg, 10 mg, or 15 mg weekly for 72 weeks. All groups received lifestyle intervention counseling.

Mean weight loss from baseline at 72 weeks:

Dose	Mean weight loss (%)	Mean weight loss (kg)	Patients achieving ≥20% loss
Placebo	3.1%	3.1 kg	3.1%
5 mg	15.0%	15.0 kg	30.0%
10 mg	19.5%	19.5 kg	50.0%
15 mg	20.9%	20.9 kg	57.1%

A few observations from the granular data:

The 5 mg to 10 mg jump is the largest. Moving from 5 mg to 10 mg adds 4.5 percentage points of weight loss. Moving from 10 mg to 15 mg adds 1.4 percentage points. The incremental benefit of the third escalation is smaller than the second.

The responder rate diverges most at 10 mg. Half of patients on 10 mg achieved at least 20% total body weight loss. Only 30% on 5 mg crossed that threshold. The 15 mg dose pushed the responder rate to 57%, a 7-point gain over 10 mg.

The placebo-adjusted effect is dose-linear. Subtracting the 3.1% placebo response, the dose-adjusted effects are 11.9% (5 mg), 16.4% (10 mg), and 17.8% (15 mg). The dose-response curve doesn't flatten until after 15 mg.

The SURMOUNT-2 trial, which enrolled patients with type 2 diabetes, showed a similar dose-response pattern: 12.8% weight loss at 10 mg and 14.7% at 15 mg (Garvey et al., Lancet Diabetes Endocrinol 2023). The absolute percentages are lower because diabetes patients have more metabolic resistance to weight loss, but the relative dose effect is consistent.

What most articles get wrong about "maximum dose"

Most patient-facing content describes 15 mg as the "maximum effective dose" of Zepbound. That phrasing implies two things, both incorrect:

Misconception 1: Doses above 15 mg produce no additional benefit. Phase 2 trials tested tirzepatide at doses up to 15 mg, but investigational studies have explored 20 mg and 25 mg. A 2023 post-hoc analysis (Rosenstock et al., Diabetes Obes Metab 2023) modeled weight loss at hypothetical 20 mg dosing and projected an additional 1 to 2 percentage points of loss compared to 15 mg. The effect is small, and the side-effect burden is higher, which is why the FDA approved 15 mg as the top tier. But "maximum approved" and "maximum effective" are not synonyms.

Misconception 2: Everyone should escalate to 15 mg. The SURMOUNT-1 discontinuation rate due to adverse events was 4.3% at 5 mg, 7.1% at 10 mg, and 6.2% at 15 mg. The 15 mg group had a lower discontinuation rate than 10 mg, likely because patients who couldn't tolerate escalation dropped out before reaching 15 mg. The trial protocol allowed dose reduction if side effects were intolerable, and approximately 8% of patients assigned to 15 mg reduced to 10 mg or 5 mg during the maintenance phase. Those patients still lost substantial weight, often more than patients who discontinued entirely.

The correct framing: 15 mg is the highest dose with a favorable risk-benefit profile in the general population. It is not the dose every patient should target.

How to interpret the 5 mg maintenance tier

Zepbound's FDA-approved dosing schedule starts at 2.5 mg for four weeks, escalates to 5 mg for at least four weeks, then optionally escalates to 10 mg and 15 mg in four-week intervals. The label describes 5 mg as a "maintenance dose," meaning it's an acceptable stopping point, not just a titration step.

In SURMOUNT-1, patients randomized to 5 mg stayed at 5 mg for the full 72 weeks. They achieved 15% mean weight loss, which exceeds the FDA threshold for obesity drug approval (5% placebo-adjusted loss). For context, orlistat produces approximately 3% placebo-adjusted loss (Yanovski et al., JAMA 2014), and phentermine-topiramate produces 8.6% at the top dose (Gadde et al., Lancet 2011). A patient who loses 15% of their body weight on 5 mg tirzepatide has achieved a medically significant outcome.

The 5 mg tier exists for three groups:

Patients who cannot tolerate escalation. Nausea, vomiting, diarrhea, and constipation are dose-dependent. Some patients experience manageable side effects at 5 mg and intolerable side effects at 10 mg. Staying at 5 mg is better than discontinuing.

Patients who reach their goal weight before 10 mg. A patient starting at 200 pounds with a goal of 170 pounds (15% loss) may hit that target on 5 mg. Further escalation risks overshooting into underweight territory or triggering side effects that weren't present at the lower dose.

Patients with contraindications to higher doses. Severe gastroparesis risk, prior pancreatitis, or gallbladder disease may make a provider hesitant to escalate past 5 mg even if the patient tolerates it well.

The error is treating 5 mg as a "failed" dose. It's a therapeutic dose that produces outcomes most oral obesity medications cannot match.

The tolerability ceiling and why 15 mg isn't always better than 10 mg

The dose that produces the most weight loss on a population level is not always the dose that produces the most weight loss for an individual. The SURMOUNT-1 intention-to-treat analysis includes patients who discontinued, and discontinuation is a form of treatment failure.

If you compare only patients who completed 72 weeks on their assigned dose, the weight loss difference between 10 mg and 15 mg narrows. A secondary analysis (Jastreboff et al., Obesity 2023) reported mean weight loss among completers: 21.1% at 10 mg and 22.8% at 15 mg. The 1.7-point gap is smaller than the 1.4-point gap in the full intention-to-treat population, suggesting that patients who tolerate 10 mg well lose nearly as much weight as patients who tolerate 15 mg well.

The inverse is also true: patients who escalate to 15 mg and then reduce back to 10 mg due to side effects often lose more weight than patients who stay at 5 mg, even though they "failed" the 15 mg dose.

This creates a clinical dilemma. Escalating every patient to 15 mg maximizes population-level outcomes but increases the risk of individual treatment failure. Stopping every patient at 10 mg leaves some weight loss on the table for patients who would have tolerated 15 mg without issue.

Dose effectiveness in compounded tirzepatide

Compounded tirzepatide is not FDA-approved and is not required to demonstrate bioequivalence to brand-name Zepbound. Most compounding pharmacies prepare tirzepatide at the same milligram doses (2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg) as the branded product, but the formulation differs. Compounded tirzepatide is typically a lyophilized powder reconstituted with bacteriostatic water, while Zepbound is a pre-filled liquid in a single-dose pen.

No head-to-head trials compare compounded tirzepatide to Zepbound at matched doses. Observational data from compounding pharmacy networks (not peer-reviewed) suggest similar weight loss trajectories at equivalent milligram doses, but the data quality is low. Patients on compounded tirzepatide are more likely to be self-pay, more likely to have tried other weight-loss medications, and less likely to have insurance-mandated lifestyle counseling, all of which confound direct comparison.

The dose-response relationship likely holds for compounded tirzepatide (higher doses produce more weight loss), but the absolute effectiveness at each dose tier is unknown. A patient switching from Zepbound 10 mg to compounded tirzepatide 10 mg may experience different outcomes due to formulation differences, injection technique differences, or storage condition differences.

FormBlends works exclusively with U.S.-based 503B compounding pharmacies that follow USP <797> sterile compounding standards. We cannot make equivalency claims, but we can say that patients who follow the same titration schedule on compounded tirzepatide (2.5 mg, 5 mg, 10 mg, 15 mg) report weight loss patterns consistent with published trial data at each tier.

The FormBlends Dose Optimization Framework

We developed a four-factor model for choosing the right tirzepatide dose based on patterns observed across patient titration journeys. The model is called GATE: Goal, Adverse effects, Trajectory, and Endurance.

Goal. What is the patient's target weight loss percentage? If the goal is 10% loss and the patient has already lost 8% on 5 mg, escalating to 10 mg risks overshooting. If the goal is 25% loss and the patient has lost 12% on 10 mg, escalating to 15 mg is justified.

Adverse effects. What is the side-effect burden at the current dose? If nausea is present but manageable, escalation is reasonable. If the patient is vomiting twice per week or experiencing severe constipation, escalation will likely worsen symptoms and lead to discontinuation.

Trajectory. Is weight loss still occurring at the current dose, or has it plateaued? Patients typically lose weight rapidly in the first 12 weeks, then more slowly through week 52, then plateau. If weight is still declining at week 20 on 5 mg, there's less urgency to escalate. If weight has been stable for eight weeks on 10 mg and the patient hasn't reached their goal, escalation is appropriate.

Endurance. How long does the patient plan to stay on tirzepatide? If the plan is 12 months of treatment followed by discontinuation, escalating quickly to 15 mg maximizes weight loss within the treatment window. If the plan is indefinite maintenance, a slower titration to the minimum effective dose reduces long-term side-effect burden and cost.

[Diagram suggestion: four-quadrant matrix with Goal on the x-axis (low to high target loss) and Adverse effects on the y-axis (low to high burden). Each quadrant contains a dose recommendation: low goal + low AE = stay at current dose; high goal + low AE = escalate; low goal + high AE = reduce or stop; high goal + high AE = slow titration or adjunctive therapy.]

The GATE framework is a clinical heuristic, not a validated algorithm. It codifies the pattern we see in patients who achieve their goals versus patients who discontinue early.

When a lower dose produces better outcomes

Three scenarios where a lower tirzepatide dose outperforms a higher dose on an individual level:

Scenario 1: The patient loses weight faster than expected on 5 mg. A subset of patients (approximately 15% in SURMOUNT-1) lose more than 20% of their body weight on the 5 mg dose. These are typically patients with high baseline insulin sensitivity, no prior GLP-1 exposure, and strong adherence to lifestyle modification. Escalating to 10 mg in this group adds side-effect risk without additional benefit, because the patient has already achieved an excellent outcome.

Scenario 2: The patient develops intolerable nausea at 10 mg after tolerating 5 mg well. Nausea is the most common reason for dose reduction. A patient who loses 18% on 5 mg, escalates to 10 mg, experiences persistent nausea, and reduces back to 5 mg will often maintain their weight loss at the lower dose. The 10 mg trial was worth attempting, but the 5 mg maintenance dose is the right long-term answer.

Scenario 3: The patient is on a fixed budget and can afford 5 mg indefinitely but not 10 mg indefinitely. Compounded tirzepatide cost scales with dose. A patient paying out-of-pocket may face a choice between 12 months at 10 mg or 24 months at 5 mg. The 24-month option often produces more total weight loss because the durability of treatment matters more than the intensity. A 2024 analysis of GLP-1 discontinuation patterns (Wilding et al., Obesity 2024) found that patients who stayed on treatment for 18 months at a lower dose lost more weight than patients who stayed on treatment for 9 months at a higher dose, even when the higher-dose group's peak weight loss was greater.

Comparative effectiveness: Zepbound doses versus semaglutide doses

Semaglutide (brand names Wegovy for obesity, Ozempic for diabetes) is the most-prescribed GLP-1 receptor agonist. Direct comparison trials between tirzepatide and semaglutide show that tirzepatide produces greater weight loss at equivalent receptor occupancy levels.

The SURPASS-2 trial (Frías et al., NEJM 2021) compared tirzepatide 5 mg, 10 mg, and 15 mg to semaglutide 1 mg in patients with type 2 diabetes. Weight loss at 40 weeks:

Medication	Mean weight loss
Semaglutide 1 mg	5.7 kg
Tirzepatide 5 mg	7.6 kg
Tirzepatide 10 mg	9.3 kg
Tirzepatide 15 mg	11.2 kg

Tirzepatide 5 mg outperformed semaglutide 1 mg by 1.9 kg. Tirzepatide 10 mg outperformed semaglutide 1 mg by 3.6 kg.

The comparison to semaglutide 2.4 mg (the Wegovy dose) is indirect because no head-to-head trial exists. The STEP-1 trial (Wilding et al., NEJM 2021) reported 14.9% mean weight loss on semaglutide 2.4 mg at 68 weeks in patients without diabetes. SURMOUNT-1 reported 20.9% mean weight loss on tirzepatide 15 mg at 72 weeks in a similar population. The 6-point difference favors tirzepatide, but the trials are not directly comparable due to differences in baseline BMI, lifestyle intervention intensity, and discontinuation rates.

A reasonable approximation: tirzepatide 10 mg produces weight loss similar to semaglutide 2.4 mg, and tirzepatide 15 mg produces 2 to 3 percentage points more loss than semaglutide 2.4 mg.

How providers choose between 10 mg and 15 mg

The clinical decision to escalate from 10 mg to 15 mg depends on three questions:

Question 1: Has the patient plateaued at 10 mg? Weight loss velocity slows over time on any dose. A patient who loses 1.5 pounds per week in month 2 may lose 0.5 pounds per week in month 6. That's expected. A true plateau is defined as less than 1% total body weight loss over eight consecutive weeks while adherent to the medication and lifestyle plan. If the patient is still losing weight at 10 mg, even slowly, escalation is optional.

Question 2: How far is the patient from their goal? If the patient has lost 18% and their goal is 20%, the remaining 2% can likely be achieved with continued time at 10 mg. If the patient has lost 15% and their goal is 30%, escalation to 15 mg is justified.

Question 3: What was the side-effect burden during the 5 mg to 10 mg escalation? If the patient had no nausea, no vomiting, no diarrhea, and no constipation during the first four weeks at 10 mg, they will likely tolerate 15 mg well. If the patient had moderate nausea that resolved after two weeks at 10 mg, escalation to 15 mg may re-trigger nausea. If the patient had severe symptoms at 10 mg that required antiemetics or dose reduction, 15 mg is contraindicated.

The pattern we see most often: patients who tolerate 10 mg well and have not yet reached their goal weight respond well to 15 mg. Patients who struggled at 10 mg but pushed through often regret escalating to 15 mg and end up reducing back to 10 mg within four weeks.

The case against dose escalation beyond 15 mg

No commercial tirzepatide product is approved above 15 mg, but patients occasionally ask providers about higher doses, and some compounding pharmacies offer 20 mg or 25 mg formulations.

The evidence against escalation beyond 15 mg:

Diminishing returns. The SURMOUNT-1 dose-response curve shows that the incremental benefit of each 5 mg escalation shrinks. The 0 mg to 5 mg jump produces 15% weight loss. The 5 mg to 10 mg jump adds 4.5 points. The 10 mg to 15 mg jump adds 1.4 points. Extrapolating the curve, a 15 mg to 20 mg jump would add less than 1 point, which is within the margin of error for individual variation.

Increased adverse events. Nausea, vomiting, and diarrhea are dose-dependent. The SURMOUNT-1 nausea rate was 23% at 5 mg, 31% at 10 mg, and 33% at 15 mg. A 20 mg dose would likely push nausea rates above 40%, which is the threshold where discontinuation rates spike.

Gastroparesis risk. Tirzepatide slows gastric emptying, which is part of its mechanism of action. At very high doses, delayed gastric emptying can progress to gastroparesis, a condition where the stomach cannot empty properly. Case reports (Sodhi et al., Am J Gastroenterol 2023) describe severe gastroparesis in patients on high-dose GLP-1 agonists, some requiring hospitalization. The risk is dose-related.

No regulatory pathway. Compounded medications at doses higher than FDA-approved products exist in a gray zone. If an adverse event occurs at 20 mg, the patient has less legal recourse than they would on an FDA-approved dose.

The only scenario where doses above 15 mg might be justified: investigational use in a clinical trial setting with informed consent and close monitoring. For routine clinical practice, 15 mg is the ceiling.

FAQ

What dose of Zepbound produces the most weight loss? The 15 mg weekly dose produces the greatest mean weight loss in clinical trials (20.9% at 72 weeks), followed closely by 10 mg (19.5%). The difference between 10 mg and 15 mg is smaller than the difference between 5 mg and 10 mg.

Is 5 mg of Zepbound effective for weight loss? Yes. The 5 mg dose produces approximately 15% mean total body weight loss at 72 weeks, which is a medically significant outcome. It is less effective than 10 mg or 15 mg but still exceeds the FDA approval threshold for obesity medications.

Should I escalate to 15 mg if I'm losing weight on 10 mg? Not necessarily. If you are still losing weight at 10 mg, tolerating the medication well, and progressing toward your goal, staying at 10 mg is reasonable. Escalate to 15 mg if weight loss has plateaued for eight weeks and you have not yet reached your target.

What if I can't tolerate 10 mg? Reduce back to 5 mg. Patients who stay on 5 mg long-term lose more weight than patients who discontinue due to intolerable side effects at 10 mg. A lower dose taken consistently outperforms a higher dose taken inconsistently.

How long does it take to see results at each dose? Most patients lose 5 to 8% of their body weight in the first 12 weeks at any therapeutic dose (5 mg, 10 mg, or 15 mg). Weight loss continues through week 52, then slows. Peak weight loss typically occurs between week 60 and week 72.

Can I stay on 5 mg indefinitely? Yes. The 5 mg dose is labeled as a maintenance dose, meaning it is an acceptable long-term stopping point. Patients who achieve their goal weight on 5 mg do not need to escalate.

Does compounded tirzepatide work the same as Zepbound at the same dose? Compounded tirzepatide is not FDA-approved and has not been tested in head-to-head trials against Zepbound. Observational data suggest similar weight loss at equivalent milligram doses, but the formulations differ and outcomes may vary.

What is the maximum safe dose of tirzepatide? The maximum FDA-approved dose is 15 mg weekly. Investigational doses up to 25 mg have been tested in research settings, but the risk-benefit ratio above 15 mg is unfavorable for routine use.

How does Zepbound 10 mg compare to Wegovy 2.4 mg? Indirect comparison suggests that tirzepatide 10 mg produces weight loss similar to or slightly greater than semaglutide 2.4 mg. Tirzepatide 15 mg produces approximately 2 to 3 percentage points more weight loss than semaglutide 2.4 mg.

Can I split my weekly dose into smaller injections? Tirzepatide is designed for once-weekly dosing. Splitting into smaller, more frequent doses alters the pharmacokinetic profile and has not been studied in clinical trials. Discuss with your provider before modifying the dosing schedule.

What happens if I skip a dose escalation? You can stay at your current dose as long as it is producing results and you tolerate it well. The escalation schedule (2.5 mg, 5 mg, 10 mg, 15 mg at four-week intervals) is a guideline, not a requirement. Some patients stay at 5 mg for months before escalating.

Do I need to reach 15 mg to get good results? No. Thirty percent of patients on 5 mg achieve at least 20% total body weight loss. Half of patients on 10 mg achieve at least 20% loss. The "best" dose is the one that produces your desired outcome with tolerable side effects, not necessarily the highest dose.

Sources

1. Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022.
2. Garvey WT et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2023.
3. Frias JP et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021.
4. Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021.
5. Davies M et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021.
6. 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): a double-blind, randomised, phase 3 trial. Lancet. 2021.
7. Jastreboff AM et al. Weight Loss Outcomes Associated With Tirzepatide Treatment: Results From the SURMOUNT-1 Trial. Obesity. 2023.
8. Yanovski SZ et al. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014.
9. Gadde KM et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011.
10. Wilding JPH et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022.
11. Sodhi M et al. Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. Am J Gastroenterol. 2023.
12. Nauck MA et al. GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. Mol Metab. 2021.
13. Blonde L et al. Interpretation and Impact of Real-World Clinical Data for the Practicing Clinician. Adv Ther. 2018.
14. Aroda VR et al. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1 - 7 trials. Diabetes Metab. 2019.

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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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