Zepbound From Eli Lilly: Chronic Weight Management

Zepbound, a new prescription medicine from Eli Lilly, is a game changer for adults looking for chronic weight management or treatment for moderate-to-severe obstructive sleep apnea.

As an FDA approved medication, Zepbound contains tirzepatide, a dual GIP and GLP-1 receptor agonist that targets key hormonal pathways to control appetite and weight loss.

This page is a medically accurate and detailed look at Zepbound, including its effectiveness, comparisons to Ozempic and Wegovy, insurance coverage and safety considerations. Written by a SANEMD, this content is for patients and healthcare providers and follows legal and safety guidelines.

What is Zepbound and How Does It Work?

Zepbound is an injectable prescription medicine given weekly via a single-dose pen or single-dose vials. It’s FDA approved for adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with weight related medical conditions such as hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, or cardiovascular disease.

Also approved for adults with moderate-to-severe obstructive sleep apnea and obesity to improve sleep apnea symptoms. It’s to be used with a reduced calorie diet and increased physical activity for best results.

Tirzepatide, the active ingredient in Zepbound, activates both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptors found in brain areas that control appetite. It also decreases the amount of glucose produced by the liver as part of its mechanism of action, contributing to better blood sugar regulation.

This dual mechanism reduces calorie intake by slowing gastric emptying, increasing feelings of fullness and suppressing hunger signals. Unlike other drugs that only target the GLP-1 receptor, Zepbound’s unique action on both receptors makes it more effective for weight loss and chronic weight management. Additionally, Zepbound promotes increased insulin release from the pancreas when blood sugar levels are high, further supporting its metabolic benefits.

How Well Does Zepbound Work for Weight Loss?

Zepbound has shown impressive weight loss results in clinical trials, especially in the SURMOUNT program.

In the SURMOUNT-1 trial, patients on the highest dose of Zepbound (15 mg) lost an average of 21% of their body weight – about 52 pounds – over 72 weeks when combined with a reduced calorie diet and increased physical activity.In SURMOUNT-5, head-to-head, Zepbound resulted in 20.2% average body weight loss, beating the competition.

Zepbound’s effectiveness varies by dose with 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg and 15 mg strengths. Patients typically start Zepbound at 2.5 mg weekly and increase dose gradually to minimize side effects.

57% of patients on 15 mg lost at least 20% of their body weight and 91% lost at least 5% weight, making Zepbound one of the most effective FDA approved medications for chronic weight management, rivaling bariatric surgery results.

SANE MD Inisghts: To get the most out of Zepbound, patients should work with their healthcare provider to create a personalized reduced calorie diet and incorporate regular physical activity, such as 150 minutes of moderate aerobic exercise per week.

Zepbound vs Ozempic: What’s the Difference

Ozempic from Novo Nordisk contains semaglutide, a GLP-1 receptor agonist FDA approved for diabetes but often prescribed off label for weight loss. Zepbound is approved for chronic weight management and obstructive sleep apnea.

The main difference is in their mechanism: Zepbound’s dual GIP and GLP-1 receptor activation is a broader approach to appetite suppression compared to Ozempic’s single GLP-1 receptor focus.

Clinical trials show Zepbound is more effective for weight loss. A 2024 study in JAMA Internal Medicine found patients on tirzepatide lost 15.3% of their body weight after 12 months vs 8.3% for semaglutide.

Zepbound’s dual mechanism may also improve how the body processes sugar and fat, potentially offering more metabolic benefits.

But Ozempic has shown cardiovascular benefits in type 2 diabetes patients, which Zepbound is still studying.Patients considering Zepbound or Ozempic should talk to their healthcare provider to assess their primary health concerns, weight management vs diabetes control and insurance coverage, as Ozempic may be covered under diabetes benefits and Zepbound coverage varies.

Zepbound vs Wegovy: Which is Better?

Wegovy from Novo Nordisk also contains semaglutide and is FDA approved for chronic weight management, making it a competitor to Zepbound. Both are weekly injections but Zepbound’s dual GIP and GLP-1 receptor agonism gives it an edge.

In the SURMOUNT-5 trial, Zepbound resulted in 20.2% average body weight loss vs 13.7% for Wegovy over 72 weeks, a 47% greater relative weight loss. 31.6% of Zepbound patients lost at least 25% of their body weight vs 16.1% for Wegovy.

Wegovy has established cardiovascular benefits, reducing the risk of major events like heart attack and stroke by 20% in patients with obesity and heart disease, based on the SELECT trial. Zepbound is still studying for similar outcomes but data is not yet available.

The choice between Zepbound and Wegovy depends on individual patient needs, side effect tolerance and insurance coverage as both are expensive, Zepbound is $1,060/month and Wegovy is $1,349/month.

SANE MD Insights: Patients comparing Zepbound and Wegovy should discuss long term health goals with their healthcare provider as Zepbound may offer more weight loss while Wegovy’s cardiovascular data may be relevant for those with heart disease.

Why Won’t Insurance Cover Zepbound?

Insurance coverage for Zepbound is a major hurdle for many patients. Despite FDA approval for chronic weight management and obstructive sleep apnea, many insurance plans including Medicare don’t cover weight loss medications as obesity is perceived as a lifestyle issue rather than a chronic medical condition.

Zepbound’s list price of $1,060/month makes it unaffordable for many without coverage, but Eli Lilly offers a savings card that reduces the cost to as low as $25 for a one to three month supply for those with commercial insurance that covers Zepbound or $550 for those without coverage. Zepbound’s new 7.5 mg and 10 mg vials are priced at $499 per month through the Self Pay Journey Program, offering another cost-saving option for self-pay patients.

Denials are often due to prior authorization requirements, high cost or plans that exclude weight management medications. Some insurers may cover Zepbound for obstructive sleep apnea but not for weight loss alone, creating inconsistencies. Patients should work with their healthcare provider to submit appeals, provide medical necessity documentation or explore manufacturer assistance programs like Lilly Cares to get access.

SANE MD Insights: If insurance denies Zepbound coverage, ask your healthcare provider to submit a letter of medical necessity highlighting weight related medical problems or obstructive sleep apnea to support an appeal.

Zepbound Dosage and Administration

Zepbound is administered once weekly via subcutaneous injection in the stomach area, thigh or upper arm using a single-dose pen or single-dose vials. The starting dose is 2.5 mg, increased gradually over 4-20 weeks to target doses of 5 mg, 7.5 mg, 10 mg, 12.5 mg or 15 mg based on patient tolerance and healthcare provider guidance. Gradual titration helps to reduce common side effects like nausea and stomach problems. Zepbound is administered via a weekly injection under the skin, ensuring consistent delivery of the medication.

If a dose is missed, patients should take the missed dose within 4 days; otherwise, skip it and resume the regular schedule. Injection site rotation is recommended to prevent irritation. Healthcare providers should train patients on proper injection techniques and monitor progress regularly.

Safety and Contraindications

Zepbound is not for everyone. Zepbound should not be used by individuals who have a personal or family history of medullary thyroid carcinoma (MTC), Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) or those who have had a serious allergic reaction to tirzepatide or any of its components. Zepbound should not be used with other tirzepatide containing products or GLP-1 receptor agonists like Ozempic or Wegovy.

Warning: risk of thyroid tumors, including thyroid cancer with symptoms like a lump in the neck, hoarseness or trouble swallowing. Patients should report these to their healthcare provider immediately. Zepbound is contraindicated in patients with severe gastrointestinal diseases like gastroparesis due to its slowed emptying effects.

Common and Serious Side Effects

Common side effects of Zepbound include fatigue, nausea, vomiting, diarrhea, constipation, stomach pain, decreased appetite and injection site reactions. These are usually mild to moderate and go away with continued use. Other reported effects include hair loss, feeling tired and feeling jittery especially in patients with diabetes and low blood sugar.

Serious side effects are rare but include severe stomach problems, kidney problems due to dehydration from diarrhea or vomiting, gallbladder problems (symptoms include upper stomach pain, fever or jaundice) and severe allergic reactions (e.g. rash, swelling or difficulty breathing). Low blood sugar is a concern for patients taking Zepbound with diabetes medications like insulin or sulfonylureas with symptoms of blurry vision, shakiness or confusion.

Patients with severe pain, persistent stomach problems or signs of a serious allergic reaction should contact their healthcare provider immediately. To report side effects, patients can contact Lilly at 1-800-LillyRx or the FDA at 1-800-FDA-1088.

Special Populations and Precautions

Pregnancy and Breastfeeding

Zepbound’s safety in pregnancy is not established and may harm an unborn baby. A pregnancy exposure registry collects information on outcomes for women exposed to Zepbound during pregnancy; patients can enroll by contacting Lilly. Women should inform their healthcare provider if pregnant or planning pregnancy. It is unknown if Zepbound passes into breast milk, so breastfeeding patients should discuss with their healthcare provider.

Birth Control Considerations

Zepbound may reduce the effectiveness of birth control pills due to slowed gastric emptying. Healthcare providers may recommend alternative birth control methods, such as barrier methods, for 4 weeks after starting Zepbound and after each dose increase to ensure protection.

Patients with Diabetes

Zepbound is not approved to treat diabetes but may cause low blood sugar levels in patients taking diabetes medications. Patients with diabetic retinopathy should be monitored closely as rapid glucose changes may worsen this condition. Regular blood sugar monitoring is essential and patients should report symptoms like blurry vision or feeling jittery to their healthcare provider.

Drug Interactions

Zepbound may interact with other medicines, including diabetes medications and increase the risk of low blood sugar. It should not be used with other tirzepatide containing products or GLP-1 receptor agonists. Patients should tell their healthcare provider about all prescription medicines, over-the-counter drugs and herbal products to avoid interactions. Taking too much Zepbound or combining it with other drugs may increase side effect risks; in such cases contact a healthcare provider or Poison Control at 1-800-222-1222.

Lifestyle Integration for Optimal Results

Zepbound works best with a reduced-calorie diet and increased physical activity. Patients should work with a healthcare provider or nutritionist to create a meal plan that supports weight loss while ensuring adequate nutrition. Regular physical activity such as brisk walking or strength training enhances Zepbound’s effects and improves cardiovascular health.

SANE MD Insights: Keep a food and activity journal to track progress and identify patterns that support weight loss, share with your healthcare provider for adjustments.

Cost and Accessibility

Zepbound’s high cost – approximately $1,060 per month – is a challenge especially without insurance coverage. Eli Lilly’s savings card program can reduce costs significantly for eligible patients with commercial insurance. Single-dose vials at 2.5 mg and 5 mg are available at lower prices ($400 and $550 for a 4-week supply respectively) but not covered by insurance. LillyDirect offers Zepbound single-dose vials that have reduced pricing for self-pay patients, providing an alternative for those without insurance coverage.

Potential Risks and Monitoring

Patients taking Zepbound need to be monitored by a healthcare provider to assess weight loss, side effects and overall health. Patients with a history of kidney problems, gallbladder problems or difficulty digesting food should be closely monitored. Zepbound may exacerbate these conditions and early intervention is key. Healthcare providers should also screen for depression or suicidal ideation as these have been reported with similar medications.

Zepbound for Obstructive Sleep Apnea

In December 2024, the FDA approved Zepbound for adults with moderate-to-severe obstructive sleep apnea and obesity, the first prescription medicine for this indication. By helping with weight loss, Zepbound reduces sleep apnea symptoms such as snoring and breathing pauses and improves sleep quality and overall health. Patients with obstructive sleep apnea should talk to their healthcare provider about Zepbound’s benefits and risks to determine if it’s right for them.## Long-Term Use

Zepbound is for long-term use as weight regain is common after stopping. Clinical trials show sustained weight loss with continued use but patients need to commit to lifestyle changes for long term results. Regular follow-ups with a healthcare provider ensures Zepbound remains effective and safe over time.

Conclusion

Zepbound is a game changer for chronic weight management and obstructive sleep apnea, with better weight loss than Ozempic and Wegovy due to its dual GIP and GLP-1 receptor agonism.

Its effectiveness as seen in SURMOUNT-5 makes it the top choice for adults with obesity or weight related medical conditions. But insurance coverage, high cost and potential side effects are things to consider.

Patients should work with their healthcare provider to determine if Zepbound is right for them, to get it administered properly and to integrate lifestyle changes for optimal results. For more information or to report side effects contact Lilly or the FDA.

Healthcare Provider Note:

NOTE: This content is not a substitute for professional medical advice, diagnosis or treatment. Always consult a qualified healthcare provider with reliable, science-backed information about weight loss medications and the latest health news with any questions about your health or medications.