What Is Zepbound? The Revolutionary GLP-1 Weight-Loss Treatment Explained

Zepbound is a next-generation prescription treatment developed by Eli Lilly, approved in the USA in 2023 for chronic weight management and obstructive sleep apnoea (OSA) in adults who are living with obesity or are overweight. Its active ingredient tirzepatide, also used in Eli Lilly’s type 2 diabetes (T2D) medication Mounjaro, acts as a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, two key hormones involved in appetite regulation, digestion, and insulin secretion.

Clinical studies show Zepbound can lead to substantial weight loss with up to 91% of users achieving meaningful results and an average reduction of 22.5% after 72 weeks at the 15 mg dose. This weight loss helps reduce the severity of OSA. Zepbound also enhances insulin secretion and lowers fasting glucose, supporting better glycaemic control in those with or at risk of type 2 diabetes and improves key cardiometabolic markers by increasing HDL cholesterol, lowering systolic blood pressure, and reducing triglycerides.

Uncover the mechanism of Zepbound, its potential benefits, and important considerations.

What Is Zepbound and How Does Tirzepatide Work?

Zepbound is a once-weekly weight-loss medication formulated with tirzepatide, a synthetic peptide that, unlike other drugs in its class, mimics two key natural gut hormones, GLP-1 and GIP, which help regulate appetite, digestion, and blood sugar levels after eating.

GLP-1 is released in the lower gut after meals, particularly in response to carbohydrates and fats. It slows gastric emptying, promotes a feeling of fullness, enhances insulin secretion, and reduces glucagon levels, helping to curb hunger and regulate blood sugar.

GIP, in turn, is secreted earlier in digestion by the upper intestine, also in response to food. It stimulates insulin production and works alongside GLP-1 to support healthy metabolism and fat storage.

The insulin-stimulating effects of GLP-1 and GIP are triggered primarily when blood glucose is high. By mimicking this mechanism, Zepbound, lowers the risk of hypoglycaemia (low blood sugar).

Although it partially shares its structure with natural hormones, tirzepatide is chemically modified to last much longer in the body, with a half-life of about five days, compared to just a few minutes for the naturally occurring GLP-1 and GIP hormones. This allows for convenient once-weekly dosing and steadier, longer-lasting metabolic effects.

Zepbound’s double-action mechanism delivers impressive, dose-dependent weight loss. Clinical studies over 72 weeks show an average weight loss of:

• 16% on a 5 mg dose.
• 21.4% on a 10 mg dose.
• 22.5% on a 15 mg dose.

While most weight loss occurs gradually, many users notice reduced appetite and modest changes within the first 4–12 weeks as their dose increases.

Beyond weight loss, Zepbound offers broader health benefits. It:

• Reduces the severity of symptoms related to weight-related obstructive sleep apnoea, improving breathing and sleep quality.
• Lowers fasting and post-meal blood glucose levels with minimal risk of hypoglycaemia.
• Improves cardiometabolic markers such as HDL (“good”) cholesterol, systolic blood pressure, and triglycerides.

Early data also suggest Zepbound may reduce the risk of major heart events and kidney complications in people with type 2 diabetes.

Zepbound for Weight Loss - Officially Approved Uses

Zepbound is FDA-approved in the United States for:

• Chronic weight management in adults with obesity (BMI ≥30), or overweight (BMI ≥27) with at least one weight-related condition, such as T2D, high blood pressure, sleep apnoea, cardiovascular disease, alongside diet and exercise.
• Moderate to severe obstructive sleep apnoea in adults with obesity. Zepbound is the first and only medication approved for this use.

Zepbound is not approved for:

• Type 1 diabetes.
• Use alongside other GLP-1 receptor agonists.
• T2D,  although tirzepatide is approved for managing this condition in another drug, Mounjaro.

Zepbound should not be used in the patients with:

• A personal or family history of medullary thyroid carcinoma (MTC).
• Multiple endocrine neoplasia syndrome type 2 (MEN 2).
• Known serious hypersensitivity to tirzepatide or any ingredient in Zepbound.
• Suspected or confirmed pancreatitis.
• A suspected or confirmed pregnancy.

Special caution is recommended for patients on Zepbound with:

• Severe gastrointestinal disease like gastroparesis.
• Pancreatitis.
• Gallbladder disease.
• Kidney problems or risk of dehydration.
• Severe allergic reactions.
• Suicidal thoughts or behaviours.
• Diabetic retinopathy.

Patients taking oral medications should be aware that Zepbound can slow gastric emptying, which may affect how well these medicines are absorbed. In some cases, including those using oral contraceptives, a switch to non-oral alternatives may be necessary.

Zepbound Injection: Strengths and Ingredients

Zepbound is available in single-dose pens or vials for once-weekly subcutaneous injection. Each 0.5 mL dose contains one of the following strengths of tirzepatide, the medicine’s only active ingredient:

• 2.5 mg.
• 5 mg.
• 7.5 mg.
• 10 mg.
• 12.5 mg.
• 15 mg.

The injection solution also includes the following excipients:

• Sodium chloride.
• Sodium phosphate dibasic heptahydrate.
• Water for injection.
• Either hydrochloric acid, sodium hydroxide, or both.

Zepbound contains no preservatives.

Zepbound Dosage Schedule and Administration Instructions

Treatment with Zepbound begins at a low dose and increases gradually over time. This stepwise approach helps the body adjust, improving tolerability and reducing the risk of discontinuation due to side effects.

A typical dosing schedule starts with a 2.5 mg dose once weekly, followed by gradual increases of 2.5 mg every 4 weeks during titration. Maintenance doses usually range from 5 mg to 15 mg once weekly, depending on individual tolerance and treatment goals, with the maximum dose of 15 mg once weekly.

Zepbound is injected in the abdomen, thigh, or upper arm. It is important to rotate injection sites each week to minimise irritation.

Managing missed doses:

• If a dose of Zepbound is missed, it should be taken within 96 hours.
• If more time has passed, the missed dose should be skipped and the next dose taken as scheduled. Doses should never be taken within 72 hours of each other.
• If more than two weeks of treatment are missed, a healthcare provider should be consulted, as a lower dose may be required to restart safely.

Zepbound: Side Effects to Watch For

Clinical trial data and FDA reports indicate that the most frequently reported side effects of Zepbound are gastrointestinal. Nausea, diarrhea, and constipation are among the most common, affecting approximately 25%, 19%, and 17% of users, respectively. Indigestion, abdominal pain, and vomiting are also relatively common, reported in up to 9% of patients.

These gastrointestinal side effects are typically mild to moderate and most often occur during the dose escalation period, as the body adjusts to the medication. In many cases, symptoms improve over time or with a slower titration schedule.

Other commonly reported side effects include:

• Injection site reactions like pain, redness, or itching
• Fatigue
• Allergic-type reactions
• Hair thinning
• Heartburn and excessive gas

While serious adverse effects are much less frequent, they can be significant:

• Pancreatitis, gallbladder disease, and kidney injury have been reported.
• Severe allergic reactions, like anaphylaxis or angioedema, are rare but require immediate medical attention.
• Risk of thyroid C-cell tumours, including medullary thyroid carcinoma, though this has not been confirmed in humans.

Additional risks include low blood sugar when used alongside insulin, worsening of diabetic retinopathy, and pulmonary aspiration during deep sedation. It is also important to be aware of the potential for suicidal thoughts or behaviours. While not observed in Zepbound clinical trials, such effects have been reported with similar medications.

Improving Zepbound Treatment Results with Healthy Habits

Zepbound is a powerful tool for weight loss and metabolic health, but its gastrointestinal side effects, such as nausea, bloating, or constipation, can be uncomfortable and may lead some users to stop treatment early.

Incorporating a few healthy habits can ease these symptoms and help patients stay on track:

• Supporting gut health with a high-quality probiotic, containing well-studied strains and a substantial colony-forming units (CFU) count, to promote digestive balance and comfort
• Eating fibre-rich foods like oats, garlic, bananas, and leafy greens to support regularity and provide probiotics with proper nourishment
• Staying well-hydrated to aid digestion and reduce constipation
• Maintaining regular physical activity to improve metabolism and gastrointestinal motility
• Managing stress, as it can affect both gut function and appetite regulation.

These simple steps can make Zepbound treatment more manageable and more effective in the long run.

Learn more about Forte80™

This article has been written with information taken from supported scientific research, and its purpose is purely educational. It should not be intended as medical advice or be used in personal diagnoses. Individuals on GLP-1 weight loss drugs should work closely with healthcare providers to develop a comprehensive, holistic health plan. With proper support, including targeted supplementation for digestive health, many more people may be able to benefit from these groundbreaking medications without sacrificing comfort or quality of life.

References: 

1. https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management
2. https://www.forte80.com/blogs/news/what-are-glp-1-drugs
3. https://zepbound.lilly.com/hcp/clinical-data-weight
4. https://aasm.org/zepbound-approved-fda-first-sleep-apnea-medication/
5. https://pubmed.ncbi.nlm.nih.gov/38912654/
6. https://pubmed.ncbi.nlm.nih.gov/17498508/
7. https://pmc.ncbi.nlm.nih.gov/articles/PMC12048985/
8. https://zepbound.lilly.com/assets/pdf/zepbound_Prior_Authorization_Resource_Guide.pdf
9. https://zepbound.lilly.com/hcp/dosage
10. https://zepbound.lilly.com/weight/how-to-use
11. https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type
12. https://lifestylemedicalcenters.com/zepbound-side-effects-and-how-to-manage-them/ https://www.forte80.com/collections/forte80