Zepbound (tirzepatide) has emerged as a highly effective medication for chronic weight management, particularly due to its dual action as a GIP/GLP-1 receptor agonist. It imitates glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), two naturally occurring gut hormones. However, it is not always the best option for everyone. High costs, insurance limitations, medication shortages, and side effects can make access difficult. Others may experience side effects such as nausea, vomiting, diarrhea, and constipation or have health conditions that require alternative treatments. These factors have led many people to explore other options. This guide explores Zepbound alternatives, including other weight loss medications and natural strategies.
Understanding Zepbound
Zepbound, a brand name for tirzepatide, is a once-weekly injection approved by the FDA for chronic weight management. It belongs to the incretin-therapy prescription drug class and has demonstrated significant effectiveness in helping many people lose weight. In the SURMOUNT-1 trial, adults with obesity or overweight (without diabetes) taking tirzepatide achieved up to 22.5% average body weight reduction at 72 weeks. In addition to impressive weight loss, studies show improvements in cardiovascular risk factors and metabolic markers.
Current Availability of Zepbound
As of recent updates, Zepbound is not currently in shortage. All doses of Eli Lilly’s weight loss and diabetes medications, Zepbound and Mounjaro, are now fully available. Zepbound was previously declared in limited supply in April 2024 due to the overwhelming demand for GLP-1 receptor agonists, but Eli Lilly has since ramped up production to meet the growing needs of patients. Similarly, Mounjaro, which was first added to the FDA’s drug shortage list in 2022, has also returned to full availability.
To address these concerns, Eli Lilly announced plans to expand production. Their new Concord, North Carolina facility is expected to manufacture Zepbound and Mounjaro by the end of 2024, with products ready to ship in 2025. Additionally, the company projects producing one and a half times as many sellable doses this year compared to the same period last year.
Despite these efforts, the company still predicts that demand for Zepbound may exceed supply for the rest of the year. In light of this, it’s wise to find alternatives in case of a Zepbound shortage so that your specific dosage is ready if it is ever impacted.
Read also: Understanding Zepbound Insurance
Strategies for Maintaining Zepbound Coverage
Before seeking alternatives, some GLP-1 users have been able to win back coverage by pursuing every possible option in the confusing world of healthcare.
Appealing Lost Coverage
Bridget Roberts, 37, was reapproved for Zepbound by remaining patient and persistent. It started when the Pottsgrove, Pennsylvania, resident received a letter that her insurance company was no longer covering the GLP-1. Roberts pushed back. She called to appeal repeatedly, getting a different story each time. Her persistence finally paid off. She spoke to someone from the insurance company who told her to ask her doctor for a new prior authorization, a type of preapproval request that an insurance company sometimes requires doctors to submit before agreeing to cover a treatment. When the doctor put in the new request, her medication was approved.
Switching Diagnoses
Other GLP-1 users have successfully retained coverage by changing the diagnosis indicated on their prescriptions. Many GLP-1s are FDA approved for more than just weight loss, including type 2 diabetes, cardiovascular risk reduction, and even stroke prevention in certain populations. If your insurer canceled coverage for a weight loss medication, it is possible that it will cover the same medication for a different condition, such as sleep apnea or heart disease. A new prescription for a new condition “can make the difference between full denial and full coverage."
If someone has established cardiovascular disease and obesity or overweight, Wegovy can be prescribed under that indication. If someone has moderate to severe obstructive sleep apnea and obesity, Zepbound can be prescribed for that indication. Switching diagnoses is no guarantee of coverage, however. Insurance still may decide not to cover a medication, even if FDA indications for prescribing that medication are met.
Searching for Discounts
A variety of discounts may be available from the manufacturers. The makers of Wegovy and Zepbound offer coupons and savings cards that can considerably lower your out-of-pocket cost for as long as one year. The two GLP-1 makers have also begun to offer discounts to users who pay in cash directly.
Read also: Weight Loss Drug Coverage by Medicaid
Top 8 Zepbound Alternatives
If Zepbound is not accessible or suitable, several other weight loss injections and pills are available. Some are FDA-approved for weight loss, and others may be prescribed off-label.
Mounjaro (tirzepatide): Mounjaro contains the same active ingredient, tirzepatide, and is administered once a week as Zepbound. They also have similar side effects and doses. The major difference between these drugs is that Zepbound is FDA-approved for managing chronic weight, while Mounjaro is FDA-approved for treating type 2 diabetes. However, because the active ingredient in both medications is the same, doctors may give Mounjaro off-label to help patients manage their weight. But if you have type 2 diabetes, your insurance plan is more likely to cover Mounjaro.
Mounjaro was found to produce an average weight loss of up to 13.9% over 104 weeks in people with type 2 diabetes. Mounjaro is a dual GIP/GLP-1 receptor agonist, just like Zepbound. This describes the two gut hormones that the medication imitates: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Since Zepbound and Mounjaro have the same active component, you should expect to lose weight similarly, regardless of your brand.
Wegovy (semaglutide): Wegovy (semaglutide) is another FDA-approved weight loss medication, but it only mimics GLP-1 and is known as a GLP-1 receptor agonist, whereas Zepbound is a dual receptor agonist of GIP and GLP-1. While head-to-head studies are ongoing to confirm the differences between these two medications, indirect comparisons show that Zepbound may help people lose more weight than Wegovy. This may be due to the differences in their mechanisms of action. Wegovy, like Zepound, offers a once-weekly subcutaneous injection administration.
In a clinical trial comparing Wegovy and Saxenda, Wegovy produced more weight loss than Saxenda. Over 68 weeks, people receiving Wegovy achieved an average weight loss of 15.8 kg, compared to 6.4 kg for those in the Saxenda group. For patients with established cardiovascular disease, Wegovy may be a preferred therapy as it has demonstrated reductions in cardiovascular endpoints, specifically, as well as renal function outcomes in those with established cardiovascular disease.
Read also: Weight Loss Coverage Details
Ozempic (semaglutide): Ozempic has the same active ingredient, semaglutide, as Wegovy and is administered weekly. Unlike Zepbound, Ozempic has FDA approval to regulate blood sugar levels in people with type 2 diabetes and to reduce cardiovascular risk in those with heart disease. Like Mounjaro and Zepbound, Ozempic and Wegovy’s active ingredient was initially created to treat type 2 diabetes. The manufacturers then applied for FDA approval for weight management and marketed a different brand-name version of the medication when researchers found that it may also cause weight loss.
In a 40-week clinical trial, people with type 2 diabetes who took 2 mg of Ozempic once a week lost at least 5% of their body weight, with some participants losing almost 10%. Ozempic has a shorter list of adverse effects than Wegovy, although gastrointestinal side effects are still common. Your insurance will probably cover Ozempic if you have type 2 diabetes.
Saxenda (liraglutide): Saxenda was the first GLP-1 agonist drug approved for weight loss in the United States. It is in the same class as Wegovy and works in the body similarly to the gut hormone GLP-1. Unlike Zepbound, Saxenda is injected once daily. Saxenda, like Zepbound, has no demonstrated cardiovascular benefits. However, it’s approved for adolescents 12 years of age and older.
In clinical trials, Saxenda users dropped 5-10% of their body weight over 56 weeks. Many of the side effects of Saxenda are comparable to those of Zepbound. Saxenda is a reasonable alternative option for individuals with T2DM who cannot access Zepbound or Wegovy.
Phentermine (adipex, lomaira): Phentermine and Zepbound belong to different classes of medications. Phentermine is a generic drug that was approved in 1959. It works as an anorectic or appetite suppressant. It’s also a stimulant that helps you feel less hungry and eat less. The result is weight loss. Phentermine can be a great alternative if you’re looking for a weight loss pill. It’s available as a tablet, capsule, extended-release, or disintegrating tablet.
The main difference between Zepbound and phentermine is that Zepbound may be prescribed for long-term weight management, while phentermine is only approved for short-term use because of the possibility of dependence and other negative effects. Its common side effects include insomnia, dry mouth, and nervousness.
Contrave (naltrexone-bupropion): Contrave is a prescription medication that combines two active ingredients, naltrexone and bupropion, to help people lose weight. It works by targeting the brain’s reward and hunger systems, reducing food cravings, and controlling appetite. Unlike Zepbound, a weekly injection, Contrave is taken as two tablets in the morning and two in the evening. Contrave, like most weight-loss medications, does require a dose titration upon initiation.
Studies show that Contrave can lead to significant weight loss when combined with a reduced-calorie diet and increased physical activity. On average, patients using Contrave lose about 5% to 10% of their body weight over 56 weeks. Contrave may have similar side effects to Zepbound, such as nausea, but it may cause different side effects like increased blood pressure and insomnia. Given its lower overall efficacy, this medication is intended as an adjunct to diet and exercise in patients unable to take incretin-based therapies or Qsymia.
Qsymia (phentermine/topiramate ER): Qsymia is another oral Zepbound alternative that combines two medications: phentermine, an appetite suppressant, and topiramate, a drug initially used to treat seizures and migraines. These two medications combine to help people lose weight by decreasing appetite, which may help you to eat less. Topiramate may also promote feelings of fullness.
In a 56-week study, people using Qsymia lost 5-10% of their starting body weight. Additionally, there are differences in risks and side effects of Zepbound and Qsymia. Because Qsymia contains phentermine, which can increase heart rate, it may not be a good choice for those with specific medical conditions. Qsymia demonstrated superior weight loss at 52 weeks in comparison to placebo, with an average weight loss of 8%-10% versus 1.2% with placebo. Another benefit of this medication is that, for those without insurance coverage, single-agent formulations exist for both components of Qsymia and are typically much less expensive than the combined formulation.
Xenical (orlistat): Xenical is another oral Zepbound alternative containing the active ingredient, orlistat. It’s also known by its over-the-counter version, Alli. Unlike the other Zepbound alternatives in this list, Xenical functions differently to promote weight loss. It prevents fat from being absorbed by your body from the food you consume. However, you must take Xenical three times a day within 1 hour after a meal with fat. Clinical research showed that consuming Xenical caused participants to lose an average of 8.5% of their initial body weight. One significant drawback of Xenical’s action is that it may cause unpleasant side effects like oily stools, fecal leaks, and frequent, urgent bowel movements.
Natural Zepbound Alternatives
All weight loss medications are prescribed with a balanced diet and increased exercise. Optimizing metabolic health with a nutrient-rich and calorie-controlled diet not only helps maintain a healthy weight and control blood sugar levels; it also promotes adequate nutrition, enhances gastrointestinal and cardiovascular health, lowers inflammation, and promotes general well-being.
Eat lean proteins like fish, lean meat, and beans; incorporate fruits and vegetables; healthy fats; whole grains; and low-fat dairy alternatives. General recommendations for exercise include 150-300 minutes per week of moderate-intensity aerobic activity (such as jogging, swimming, or brisk walking) mixed with 75-150 minutes of more intense exercise. Frequent exercise has been shown to support blood pressure and weight control, enhance insulin sensitivity, support metabolic health, and improve lipid profiles, including triglyceride management and HDL levels.
While natural supplements can be used as Zepbound alternatives, it is important to discuss them with a healthcare provider before starting them. Your provider will recommend reputable supplement brands and monitor their effects and safety.
Switching from Zepbound to Another Medication
If you were prescribed Zepbound and would like to switch to another alternative, talk to your doctor. If they think it’s a good option, they’ll give you the right dose to start you on to ensure an easy transition. Switching weight loss medications can be effective if Zepbound isn’t meeting your weight loss needs. For someone interested in trialing a Zepbound alternative, the first dose of the alternative may be administered seven days after its discontinuation. Most weight loss medications require some dose titration up to an efficacious or tolerated dose, and those titration schedules should be followed when initiating an alternative.
Considerations When Choosing an Alternative
When choosing a medication for weight loss, several considerations must be made. First is efficacy, where the incretin-based therapies rise above other options. Aside from efficacy, other considerations for individuals include cost to the patient, contraindications, other concomitant health conditions, side effects, and patient preference. Initiate medications like Zepboud or its alternatives should be part of a shared decision-making process with a healthcare provider, in which all aspects of weight loss are reviewed-efficacy versus side effects, cost, patient preferences, and long-term sustainability.
Addressing Concerns about Compounded Tirzepatide
With the FDA declaring the Zepbound shortage over, compounding pharmacies are required to stop making tirzepatide. This has caused concern among patients who rely on these compounded alternatives. Many patients have been stocking up on compounded tirzepatide, but the long-term availability remains uncertain.
Eli Lilly sells Zepbound vials at a discount for people not using insurance. The standard forms of Zepbound, which come in an auto-injector pen, can cost more than $1,000 per month without insurance.
Some people are talking online about buying the active ingredient from China and mixing the obesity drugs in their homes. They call it the "gray market." Zepbound and the compounded alternatives have to be sterile for injection, so a homemade version would be challenging to make safely.
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