What is replacing Zepbound? Exploring alternatives and next-generation medications

October 11, 2025 •

3 min read

As of mid-2025, insurance companies like CVS Caremark have begun removing Zepbound from their preferred formularies, leading many patients to question what is replacing Zepbound. This market shift is driven by new negotiations and a pipeline of even more advanced weight management therapies.

Quick Summary

Several alternatives are emerging as the landscape of weight loss medication evolves. Options include comparable injectables like Wegovy, new oral medications in development, and next-generation drugs that promise enhanced efficacy.

Key Points

Wegovy as a primary alternative: Due to insurance changes, Wegovy (semaglutide) is becoming the favored formulary choice over Zepbound for many patients.
Next-generation triple agonists: Investigational drugs like retatrutide are being developed by Eli Lilly, targeting three hormone receptors and demonstrating potentially superior weight loss to Zepbound in early trials.
Oral alternatives are coming: The development of oral GLP-1 pills, such as Eli Lilly’s orforglipron, offers a convenient and effective option for patients who prefer to avoid injections.
Monthly injection options: Amgen's MariTide is a monthly injectable in clinical trials, with a potential benefit of sustaining weight loss after discontinuation.
Older oral medications: Established oral weight loss drugs like Qsymia and Contrave are available but typically result in less weight loss than newer injectable GLP-1 agonists.
Personalized treatment is key: The best alternative is highly individual and should be determined in consultation with a doctor, considering efficacy, side effects, and coverage.
Cardiovascular benefits: Wegovy is FDA-approved for reducing cardiovascular risk, an important consideration for patients with heart disease.

Immediate Alternatives to Zepbound

For patients needing an alternative to Zepbound, several FDA-approved medications are available, with choices often depending on insurance coverage, side effect tolerance, and administration preference. Zepbound's active ingredient, tirzepatide, targets both GIP and GLP-1 receptors, while alternatives may target these individually or in different combinations.

Wegovy (Semaglutide)

Wegovy is a common prescribed alternative, especially after major pharmacy benefit managers like CVS Caremark updated their formularies. It is a once-weekly injectable GLP-1 receptor agonist. Clinical trials show Wegovy leads to an average weight loss of about 15% of body weight, less than Zepbound's average of over 20% in comparative trials. For patients with cardiovascular disease, Wegovy is also FDA-approved to reduce major adverse cardiovascular events.

Saxenda (Liraglutide)

Saxenda is a once-daily injectable GLP-1 medication, generally considered less potent than newer weekly options.

Mounjaro (Tirzepatide)

Mounjaro contains the same active ingredient as Zepbound (tirzepatide) and is FDA-approved for type 2 diabetes. It may be prescribed off-label for weight loss in patients with both conditions if insurance covers it for diabetes.

Oral Alternatives to Zepbound

For those who prefer not to use injections, oral medications are available, although they typically result in less weight loss than injectable options.

Qsymia (Phentermine/Topiramate ER): This combination pill suppresses appetite and increases fullness.
Contrave (Naltrexone/Bupropion): This medication combines an opioid antagonist and an antidepressant to help reduce appetite and cravings.
Xenical/Alli (Orlistat): Available both over-the-counter (Alli) and by prescription (Xenical), Orlistat blocks fat absorption. It offers more modest weight loss and can cause gastrointestinal side effects.

The Next Generation of Weight Loss Medications

A new wave of medications is in development, aiming for higher efficacy and easier administration.

Triple-Action Agonists

Eli Lilly's retatrutide is a promising 'triple-G' agonist targeting GLP-1, GIP, and glucagon receptors. Phase 2 trials showed significant weight loss. Phase 3 data is expected in 2025, potentially leading to FDA approval around 2027.

Oral GLP-1 Pills

Oral options are being developed by both Novo Nordisk and Eli Lilly to compete with injections. Eli Lilly's orforglipron, a once-daily oral GLP-1 agonist, showed promising Phase 2 results. An FDA submission is anticipated in late 2025, potentially making it available as early as 2026. Novo Nordisk is also developing an oral version of semaglutide (oral Wegovy), with an FDA decision expected in late 2025.

Alternative Injection Protocols

Amgen is developing MariTide, a once-monthly injectable. Early Phase 2 data showed average weight loss and potential sustained weight loss after treatment stops. More information can be found at {Link: SingleCare blog https://www.singlecare.com/blog/zepbound-alternatives/}.

A Comparison of Zepbound and Alternatives

A table comparing Zepbound and several alternatives based on features like mechanism, administration, and average weight loss is available from {Link: SingleCare blog https://www.singlecare.com/blog/zepbound-alternatives/} and {Link: NiceRx blog https://www.nicerx.com/blog/zepbound-alternatives/}.

Conclusion

The weight management medication landscape is changing rapidly, with Zepbound facing challenges from both existing drugs and promising new treatments in development. The full range of options and considerations are detailed in resources from {Link: SingleCare blog https://www.singlecare.com/blog/zepbound-alternatives/} and {Link: NiceRx blog https://www.nicerx.com/blog/zepbound-alternatives/}. Choosing the right alternative requires consulting a healthcare provider to consider individual needs, health conditions, and preferences. For more detailed information, resources like the Obesity Medicine Association provide valuable guidance.

Frequently Asked Questions

The most direct alternative is Wegovy (semaglutide), a once-weekly injectable GLP-1 agonist. For patients with type 2 diabetes, Mounjaro (tirzepatide), which has the same active ingredient as Zepbound, may also be prescribed off-label for weight loss if medically appropriate and covered by insurance.

While new oral GLP-1 drugs like orforglipron are in development, currently available oral options like Qsymia and Contrave are less potent than injectable GLP-1s and have different mechanisms and side effect profiles. The choice depends on individual factors and preferences.

Insurance providers often update their preferred drug lists (formularies) based on negotiations with pharmaceutical manufacturers and clinical reviews. For example, CVS Caremark decided to remove Zepbound from its formulary in favor of Wegovy as of July 1, 2025, to manage costs while ensuring access to a clinically similar alternative.

Retatrutide is a potential next-generation weight loss medication from Eli Lilly that acts as a triple agonist (GLP-1, GIP, and glucagon). It is currently in Phase 3 clinical trials, with FDA approval potentially occurring around 2027 following data release in 2025.

Wegovy is FDA-approved to reduce the risk of major cardiovascular events in adults with heart disease and obesity or overweight. Zepbound's cardiovascular outcomes are still under investigation, so Wegovy may be a preferred option for patients with established heart disease.

Yes, if you previously tried and failed on Wegovy due to either intolerability or insufficient weight loss, you may be eligible to request a formulary exception for Zepbound coverage, but this process requires your healthcare provider to submit specific documentation to your insurer.

Yes, while Zepbound's FDA approval for OSA remains, insurance companies may transition patients to a preferred alternative like Wegovy based on formulary rules. The mechanism of action for OSA improvement in these medications is attributed to weight loss, and some plans may require a trial of Wegovy first.