What Is Zepbound? A Comprehensive Guide

Drugs for weight management are gaining popularity worldwide among individuals looking to achieve weight loss. Following the success of Wegovy and Ozempic, Zepbound has emerged as a new option. This medication, with the active ingredient tirzepatide, received FDA approval in November 2023 for the U.S. market.

In this article, we answer the question: what is Zepbound? We provide a comprehensive guide about its benefits, expected effects, risks, and side effects so you can make an informed decision about your weight loss journey.

What is Zepbound?

Zepbound is a new weight loss drug developed by Eli Lilly and Company. This medicine was approved in November 2023 by the Food and Drug Administration (FDA) for use in the U.S. market.

It is designated for chronic weight management in adults with obesity or overweight, with an initial body mass index (BMI) of 30 kg/m² or greater (obesity). It can also be used in individuals with a BMI of 27 kg/m² or greater (overweight) if the patient presents at least one weight-related medical problem, such as type 2 diabetes, cardiovascular disease, high blood pressure, or obstructive sleep apnea, among others.

The drug is currently available in six different dosages ranging from 2.5 mg to 15 mg and should be administered once per week through injection. To lose weight, the drug should be used with a reduced-calorie diet and increased physical activity.

The active ingredient of Zepbound is tirzepatide, which has been previously used in another drug developed by Eli Lilly and Company, Mounjaro, for adults with type 2 diabetes, approved in May 2022. Due to its active ingredient, Zepbound belongs to the drug class of GLP-1 receptor agonists (glucagon-like peptide-1 receptor agonists) and GIP receptor agonists (glucose-dependent insulinotropic polypeptide receptor agonists).

Currently, the pharmaceutical company is evaluating the effectiveness of the active ingredient of Zepbound for the treatment of obstructive sleep apnea (OSA).

How Zepbound works

The active ingredient of Zepbound is tirzepatide. This synthetic peptide is a dual agonist of human glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. GLP-1 is a hormone that stimulates the pancreas to produce insulin and regulates the secretion of glucagon (a hormone that increases blood sugar levels).

This weight loss drug targets both receptors, leading to the release of insulin from the pancreas and the reduction of hyperglycemia (high blood glucose levels). It also increases the levels of adiponectin. Adiponectin is a protein hormone involved in several metabolic processes. Its high levels are associated with a decreased risk of type 2 diabetes and cardiovascular diseases.

Thanks to targeting two mechanisms, Zepbound manages blood sugar levels and slows down stomach emptying, increasing the feeling of satiety and reducing apatite, which might support the weight management efforts of individuals who aim to lose weight.

Tirzepatide is characterized by good bioavailability — 80% of administered drugs reach the bloodstream having an active effect. It reaches the highest concentration in the blood between 8 and 72 hours after injection. The half-life of this active ingredient is approximately 5 days. This means that it will take approximately 5 days for the body to reduce the concentration of Zepbound in the system by half.

Effectiveness of Zepbound

The efficacy of the active ingredient of Zepbound, tirzepatide, has been studied in several clinical trials sponsored by Eli Lilly and Company on individuals with excess weight.

• Clinical trial SURMOUNT-1 (NCT04184622) assessed the effect of tirzepatide on 2,539 adult patients with obesity or overweight and at least one weight-related comorbid condition with a mean body weight using either 5 mg, 10 mg, or 15 mg of the drug or placebo weekly for 72 weeks. The average weight loss was between 15% and 20.9% among participants, depending on the dosage. Patients also experienced a reduction in waist circumference and cardiovascular risk factors like LDL cholesterol or triglycerides.
• Clinical trial SURMOUNT-2 (NCT04657003) assessed the effect of the active ingredient of Zepbound on 938 adult patients with body mass index ≥27 kg/m2 and type 2 diabetes. The participants received either 10 mg or 15 mg of tirzepatide or a placebo for 72 weeks. Administration of tirzepatide resulted in a reduction between 12.8% and 14.7% of excess weight.
• Clinical trial SURMOUNT-3 (NCT04657016) assessed the effect of tirzepatide on 579 participants after a 12-week lead-in period with diet and exercise. The participants who received either 10 mg or 15 mg of the drug achieved at least 5% weight loss. Patients receiving tirzepatide experienced an average weight loss of 18.4%, a reduction in cardiovascular risk factors, and an improvement in their physical function.
• Clinical trial SURMOUNT-4 (NCT04660643) assessed the efficacy of tirzepatide on 783 participants. The study aimed to learn about how tirzepatide maintains body weight loss. After 36 weeks of treatment, patients either continued receiving the medication or switched to a placebo. The patients who received a placebo gained weight and increased waist circumference, while those who continued the treatment lost approximately 5.5% of their body weight.

Overall, clinical trials have shown that taking tirzepatide has resulted in average weight loss and reduction of risk factors for cardiometabolic diseases. However, individuals taking Zepbound might require additional pharmacological support and changes in lifestyle, such as a reduced-calorie diet or exercise, to maintain weight loss after the treatment.

Safety and side effects of Zepbound

According to the package insert of Zepbound, side effects include:

• Abdominal pain
• Constipation
• Diarrhea
• Fatigue
• Injection site reactions
• Nausea
• Vomiting
• Others

Clinical studies SURMOUNT-3, and SURMOUNT-4 have evaluated in detail the side effects and tolerability of tirzepatide. According to the provided effects, over 80% of participants receiving the weight loss medication have reported at least one adverse effect. This includes, among others, nausea (35.5% of participants), diarrhea (21.1%), constipation (20.7%), vomiting (16.3%), fatigue (6.78%), or injection site reaction (8.18%).

It is important to monitor the side effects while taking Zepbound. You might discuss potential strategies that would help minimize these side effects with a healthcare professional. This might include consuming foods that won’t irritate your digestive system, drinking plenty of fluids to prevent dehydration, as well as adding physical activity to your daily routine.

Side effects requiring immediate medical attention

According to the package insert of Zepbound, it may cause serious side effects. Clinical studies SURMOUNT-3 and SURMOUNT-4 showed that serious adverse effects affected 2–5% of participants.

If you experience any of the side effects described below, seek medical attention:

• Severe stomach pain
• Kidney problems, including kidney failure
• Gallbladder problems
• Inflammation of the pancreas (pancreatitis)
• Serious allergic reactions such as swelling of the face area, difficulties with breathing, or very rapid heart rate
• Low blood sugar (hypoglycemia)
• Changes in vision in people with type 2 diabetes
• Depression or thoughts of suicide

According to the box warning issued for Zepbound, this weight loss drug might cause tumors in the thyroid, including thyroid cancer, with symptoms including a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath.

Drug interactions

Zepbound might also interact with certain drugs. You should discuss with your healthcare provider if you take any of these medications:

• Other GLP-1 agents. Tirzepatide lowers blood sugar levels; therefore, it should not be taken with other medications targeting GLP-1, such as semaglutide or liraglutide, as co-administration might potentially lead to hypoglycemia.
• Birth control pills. Tirzepatide lowers the efficacy of oral contraceptive pills. Patients should use a non-oral contraceptive for 4 weeks after starting the medication and every time the dose is increased.

It is worth mentioning that tirzepatide delays stomach emptying, and this might affect the absorption and effectiveness of other drugs administered orally. If you are taking any medication, discuss with a healthcare professional if it can be affected during the treatment with Zepbound.

Cost and availability

Zepbound is currently available in the United States and can be found at most major pharmacies, available with prescription only. Zepbound is not currently available in Europe. Mounjaro is a tirzepatide-containing drug developed by Eli Lilly and Company, which has authorization for the European market for the treatment of type 2 diabetes. It is used as a weight loss drug off-label.

The price of the drug might be relatively high if it is not covered by insurance. It is important to speak to your insurance provider as prices can vary according to the insurance coverage and your treatment plan.

Additionally, pharmacy pricing can vary. Different pharmacies might offer Zepbound at different prices due to factors like supply agreements and geographical location. You should discuss this with your healthcare provider, who will help you determine if Zepbound is the right medication for you.

Precautions and contraindications

Zepbound is not suitable for everyone. Certain individuals should avoid taking the weight loss medication as the efficacy and safety of this drug have not been tested on pregnant and breastfeeding individuals, people under the age of 18, and those with health conditions or a history of certain conditions like pancreatitis.

Zepbound has been approved for individuals who are overweight and have weight-related medical problems, such as type 2 diabetes. It is important to note that Zepbound is not approved for other forms of diabetes, such as type 1 diabetes or latent autoimmune diabetes.

Tirzepatide, like other GLP-1 receptor agonists, has been associated with an increased risk of thyroid tumors. Therefore, the weight loss drug should not be taken by individuals who:

• Have a personal or family history of medullary thyroid carcinoma (MTC)
• Have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Have had a serious reaction to tirzepatide or other ingredients of Zepbound

Final word

In the last year, weight loss drugs have become increasingly popular among individuals with obesity and weight-related medical problems. With its active ingredient, tirzepatide, Zepbound represents a promising option as it targets two receptors involved in regulating blood sugar levels and potentially targets fat metabolism, helping to lose excess weight.

It is important to remember that this type of medication should be taken under the supervision of a healthcare professional. While Zepbound helps with weight loss, it might lead to various side effects, including digestive discomfort, allergies, or injection site reactions.

Combining Zepbound with a reduced-calorie diet and enhanced physical activity is important to potentiate its effects.