Zepbound

Zepbound (tirzepatide) is an FDA-approved, once-weekly injectable medication for chronic weight management in adults with obesity or those who are overweight with at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol. It is intended for use alongside a reduced-calorie diet and increased physical activity.

Zepbound represents a significant advancement by being the first and only dual Glucose-dependent Insulinotropic Polypeptide (GIP) and Glucagon-like Peptide-1 (GLP-1) receptor agonist.

GLP-1 Agonism: Similar to other medications in this class (like semaglutide in Wegovy and Ozempic, and liraglutide in Saxenda), Zepbound activates the GLP-1 receptor. This helps to reduce appetite, enhance the feeling of fullness (satiety), slow gastric emptying, and improve insulin secretion.

GIP Agonism: The addition of GIP activity is the key difference. GIP is another naturally occurring gut hormone that complements the actions of GLP-1 by further improving metabolic control, enhancing insulin sensitivity, and contributing to reduced hunger and increased fat metabolism. This unique dual-pathway approach is believed to be the driving force behind its enhanced efficacy compared to single-agonist treatments.

Comparison: Zepbound vs. Ozempic, Wegovy, and Saxenda

| Feature | Zepbound (Tirzepatide) | Wegovy/Ozempic (Semaglutide) | Saxenda (Liraglutide) |

| Mechanism | Dual GIP and GLP-1 Agonist | Single GLP-1 Agonist | Single GLP-1 Agonist |

| Average Max. Weight Loss (Trials)* | Up to 22.5% of body weight | Up to 15% of body weight | ~8% – 10% of body weight |

| Dosing Frequency* | Once-Weekly Injection | Once-Weekly Injection | Once-Daily Injection |

| FDA Status for Weight Loss | Approved for Chronic Weight Management (Adults) | Approved for Chronic Weight Management (Wegovy) / Diabetes (Ozempic) | Approved for Chronic Weight Management (Adults/Adolescents) |

Superior Weight Loss Efficacy:

Clinical trials have demonstrated that Zepbound is associated with the highest average weight loss among the currently available injectables. Head-to-head data has shown Zepbound can result in nearly double the average weight loss compared to Wegovy (semaglutide) in some studies. This greater efficacy can translate to more significant improvements in weight-related health issues.

Improved Metabolic Control (GIP/GLP-1 Synergy):

The dual-action mechanism not only promotes greater weight loss but may also offer enhanced benefits for those with underlying metabolic issues, such as insulin resistance and pre-diabetes, beyond what is achieved with GLP-1 alone.

Once-Weekly Convenience (vs. Saxenda):

Compared to Saxenda (liraglutide), which requires a daily injection, Zepbound offers the convenience of a once-weekly dosing schedule, making adherence simpler for many patients.

Potential for Specific Co-morbidity Benefits:

Emerging data suggests Zepbound may offer particular benefits for conditions like obstructive sleep apnea (OSA).

Side Effect Profile:

While the overall pattern of side effects is similar to semaglutide-based drugs—predominantly gastrointestinal issues like nausea, vomiting, diarrhea, and constipation—the frequency or intensity of initial side effects can sometimes be stronger with Zepbound due to its potent dual action. Patients must follow the prescribed gradual dose escalation (“titration”) carefully.

Restrictions on Use:

Zepbound is currently approved for adults only, whereas both Wegovy and Saxenda have FDA approval for use in adolescents aged 12 and older, offering more options for younger patients.

Cardiovascular Data:

While Zepbound has shown positive effects on cardiometabolic risk factors, Wegovy (semaglutide) currently has more established and FDA-approved data regarding the reduction of major adverse cardiovascular events (like heart attack and stroke) in adults with existing heart disease. Zepbound is still being studied for this specific outcome.

Cost and Insurance Coverage:

Like all new, brand-name injectable weight loss medications (including Wegovy and Saxenda), Zepbound can be costly, often exceeding £800 per month without insurance coverage. Coverage for weight-loss medications remains highly variable, and patients may find that their insurance plan covers one GLP-1 product (Ozempic is often covered for Type 2 Diabetes) but not others (like Zepbound or Wegovy for weight loss alone).

Important Note: Zepbound is not the same as the diabetes drug Ozempic (semaglutide), though both are sometimes used off-label for weight loss. Zepbound is specifically approved for chronic weight management. Patients should never take Zepbound with other tirzepatide-containing products (like Mounjaro) or any other GLP-1 receptor agonist. Always consult with a healthcare professional to determine if Zepbound is the right option for your specific health profile and weight loss goals.