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Zepbound (tirzepatide) is an FDA-approved injectable medication for chronic weight management in adults with obesity or overweight with weight-related health conditions. As the first dual GIP and GLP-1 receptor agonist approved for weight loss, Zepbound offers a novel approach to addressing excess weight through appetite regulation and metabolic effects. Clinical trials demonstrated substantial weight reduction, with participants losing 15-21% of body weight over 72 weeks. Understanding how Zepbound works, who should use it, proper administration, and potential side effects is essential for anyone considering this treatment option.
Quick Answer: Zepbound (tirzepatide) is an FDA-approved dual GIP/GLP-1 receptor agonist for chronic weight management in adults with obesity or overweight with weight-related conditions, administered as a weekly subcutaneous injection.
Zepbound (tirzepatide) is an injectable prescription medication approved by the FDA in November 2023 for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity. It represents a novel class of medication known as a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist.
The medication works through a dual mechanism of action. Tirzepatide activates both GIP and GLP-1 receptors, which are naturally occurring incretin hormones involved in glucose metabolism and appetite regulation. By stimulating GLP-1 receptors, Zepbound slows gastric emptying, reduces appetite, and promotes feelings of fullness after eating. The additional GIP receptor activation may enhance insulin secretion and potentially affect metabolism, though the exact contribution of GIP activation to weight loss in humans is still being studied.
Clinical trials demonstrated substantial weight reduction with Zepbound. In the SURMOUNT-1 trial, participants lost an average of 15-21% of their body weight over 72 weeks, depending on the dose used. These results exceeded those typically seen with diet and exercise alone or with many other weight management medications. The medication also showed improvements in cardiovascular risk factors including blood pressure and lipid profiles.
Zepbound is manufactured by Eli Lilly and is chemically identical to Mounjaro (tirzepatide), which is FDA-approved for type 2 diabetes management. However, Zepbound is specifically indicated and marketed for weight management at the same dosage strengths. These products should not be used together or with other GLP-1 receptor agonists or weight-loss medications unless specifically directed by a healthcare provider.
LOSE WEIGHT WITH MEDICAL SUPPORT — BUILT FOR MEN
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Zepbound is FDA-approved for adults with a body mass index (BMI) of 30 kg/m² or greater (obesity), or a BMI of 27 kg/m² or greater (overweight) with at least one weight-related comorbid condition such as hypertension, type 2 diabetes, or dyslipidemia. The medication should be used as an adjunct to a reduced-calorie diet and increased physical activity, not as a standalone treatment.
Candidates for Zepbound typically include individuals who have not achieved adequate weight loss through lifestyle modifications alone or who have weight-related health complications requiring more intensive intervention. Healthcare providers assess cardiovascular risk factors, metabolic parameters, and previous weight loss attempts when determining appropriateness. Patients should have realistic expectations and commitment to long-term lifestyle changes, as discontinuation often results in weight regain.
Zepbound is contraindicated in several important populations:
Individuals with a personal or family history of medullary thyroid carcinoma (MTC)
Patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
Those with a history of serious hypersensitivity to tirzepatide or any excipients
Zepbound should be avoided in patients with severe gastrointestinal disease, including severe gastroparesis. Use is not recommended during pregnancy or breastfeeding. If pregnancy occurs while using Zepbound, the medication should be discontinued. Women planning pregnancy should discuss timing of discontinuation with their healthcare provider.
Importantly, Zepbound may reduce the effectiveness of oral contraceptives. Women using oral contraceptives should use an additional non-oral method or add a barrier method for 4 weeks after starting Zepbound and for 4 weeks after each dose increase.
Additional caution is warranted in patients with a history of pancreatitis, diabetic retinopathy (particularly if using insulin), or renal impairment. Patients taking insulin or insulin secretagogues may require dose adjustments to minimize hypoglycemia risk. A thorough medical history and risk-benefit discussion should precede initiation, with particular attention to thyroid disease history and gastrointestinal tolerance.
Zepbound is administered as a subcutaneous injection once weekly, on the same day each week, at any time of day, with or without meals. The medication comes in single-dose prefilled pens available in six dosage strengths: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg. The pen is designed for ease of use, requiring minimal preparation and featuring an automatic injection mechanism.
The recommended dosing schedule follows a gradual escalation approach:
Initial dose: 2.5 mg once weekly for 4 weeks (this is a titration dose, not expected to provide full therapeutic effect)
Maintenance escalation: Increase by 2.5 mg increments every 4 weeks as tolerated
Maximum dose: 15 mg once weekly
Typical therapeutic doses: 5 mg, 10 mg, or 15 mg once weekly
This gradual dose escalation strategy minimizes gastrointestinal side effects, which are the most common reasons for treatment discontinuation. Patients should not increase the dose more rapidly than recommended, even if tolerating the medication well. If a dose is missed, it should be administered as soon as possible within 4 days (96 hours) of the missed dose. If more than 4 days have passed, skip the missed dose and resume the regular schedule.
You may change your weekly dosing day if at least 72 hours have passed since your last dose.
Zepbound should be injected subcutaneously in the abdomen, thigh, or upper arm, rotating injection sites with each dose to reduce the risk of lipodystrophy. The medication should be stored in the refrigerator at 36°F to 46°F (2°C to 8°C) and protected from light. Do not freeze; discard if the pen has been frozen. Pens may be kept at room temperature (up to 86°F or 30°C) for up to 21 days if needed. Do not use if the pen has been dropped or damaged.
Patients should inspect the solution before each injection—it should be clear and colorless to slightly yellow. Do not use if the solution is cloudy, discolored, or contains particles. Healthcare providers typically provide injection training at initiation and offer resources for ongoing support.
Because Zepbound delays gastric emptying, it may affect the absorption of oral medications. Patients taking medications with a narrow therapeutic index should be monitored closely, especially when starting Zepbound or increasing the dose.
The most frequently reported adverse effects of Zepbound are gastrointestinal in nature, occurring in a substantial proportion of users, particularly during dose escalation. These effects are generally mild to moderate in severity and tend to diminish over time as the body adjusts to the medication. Side effect rates are dose-dependent, with higher frequencies at higher doses.
Common gastrointestinal side effects include:
Nausea (reported in approximately 24-29% of patients)
Diarrhea (occurring in approximately 18-24% of users)
Vomiting (affecting about 8-12% of patients)
Constipation (reported in roughly 11-17% of individuals)
Abdominal pain and dyspepsia
Decreased appetite (therapeutic effect but can be excessive)
To minimize these effects, patients should eat smaller, more frequent meals, avoid high-fat or spicy foods, stay well-hydrated, and allow adequate time for dose titration. Most gastrointestinal symptoms improve within several weeks of maintaining a stable dose.
Serious but less common adverse effects require immediate medical attention:
Pancreatitis has been reported with GLP-1 receptor agonists. Patients should seek urgent care for severe, persistent abdominal pain radiating to the back, often accompanied by vomiting. If pancreatitis is suspected, Zepbound should be discontinued immediately and not restarted if pancreatitis is confirmed.
Gallbladder disease, including cholelithiasis and cholecystitis, has occurred in clinical trials, likely related to rapid weight loss. Symptoms may include right upper quadrant pain, fever, or jaundice and require prompt medical evaluation.
Hypoglycemia risk increases when Zepbound is used with insulin or sulfonylureas—dose adjustments of these medications may be necessary.
There is a boxed warning regarding thyroid C-cell tumors based on rodent studies, though relevance to humans remains uncertain. Patients should report any neck mass, dysphagia, or persistent hoarseness.
Acute kidney injury has been reported, typically in the context of severe dehydration from gastrointestinal side effects. Hypersensitivity reactions, including anaphylaxis and angioedema, though rare, necessitate immediate discontinuation.
Zepbound carries a warning for suicidal behavior and ideation. Patients should be monitored for mood changes, depression, or suicidal thoughts, particularly those with a history of depression.
Zepbound should not be used in patients with severe gastrointestinal disease, including severe gastroparesis.
Regular follow-up appointments allow for assessment of weight loss progress, tolerance, and any emerging safety concerns. Healthcare providers should counsel patients on recognizing warning signs and when to seek medical evaluation, ensuring safe and effective use of this potent weight management medication.
Zepbound is the first dual GIP and GLP-1 receptor agonist approved for weight management, offering a unique mechanism that activates two hormone pathways involved in appetite regulation and metabolism. Clinical trials showed greater weight reduction compared to many other weight management medications, with participants losing 15-21% of body weight over 72 weeks.
Yes, Zepbound is approved for adults with type 2 diabetes who meet BMI criteria for obesity or overweight with weight-related conditions. However, dose adjustments of insulin or sulfonylureas may be necessary to minimize hypoglycemia risk, and close monitoring by your healthcare provider is essential.
Discontinuation of Zepbound often results in weight regain, as the medication's effects on appetite regulation and metabolism diminish. Long-term commitment to lifestyle modifications including reduced-calorie diet and increased physical activity is essential for maintaining weight loss results.
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