Key takeaways
Zepbound’s active ingredient, tirzepatide, is a weight loss drug in the incretin-therapy prescription drug class. Most specifically, it is a dual GIP/GLP-1 receptor agonist.
Zepbound and other members of the GLP-1 medication class are highly effective weight loss drugs. Certain members of the drug class may be more desirable than others based on data from clinical trials in patients with other underlying health conditions.
Zepbound and GLP-1s come with side effects that may be intolerable to some, limitations from insurance companies in terms of prescription coverage, as well as other accessibility issues.
Alternatives to Zepbound and GLP-1 drugs are available and may be selected under the medical advice of a healthcare professional.
Overall, weight loss in obese individuals is a journey that may be supplemented with weight loss drugs, but lifestyle modifications remain the cornerstone therapy.
Zepbound (tirzepatide) is a member of the growing-in-popularity incretin-based therapies, which are generally considered first-line medications for weight loss management. In December 2024, the Food and Drug Administration (FDA) also approved Zepbound for treating obstructive sleep apnea in adults with obesity, along with a reduced-calorie diet and increased physical activity. Zepbound is a glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide 1 (GLP-1) dual receptor agonist. It is administered as a once-weekly subcutaneous injection, with doses ranging from 2.5 mg per week to a maximum of 15 mg per week. While most side effects are limited to gastrointestinal (GI) effects, like nausea, diarrhea, or constipation, certain individuals should avoid Zepbound. In addition, access to these weight loss drugs can be limited due to insurance claim denials and shortages, for which patients may seek alternatives.
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What can I take instead of Zepbound?
Candidates for weight loss medications are those who have not met their weight loss goals (loss of at least 5% of total body weight at 3 to 6 months) with lifestyle interventions and who also have a body mass index (BMI) greater than or equal to 30 kg/m2, or a BMI of 27 to 29.9 kg/m2 and one or more weight-related comorbidities.
When choosing a medication for weight loss, several considerations must be made. First is efficacy, where the incretin-based therapies rise above other options. Incretin-based therapies include the glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 (GLP-1) dual receptor agonist, Zepbound, and the GLP-1 receptor agonists, Wegovy and Saxenda. These therapies are synthetic receptor antagonists that mimic the natural GLP-1 hormone released in the gastrointestinal tract in response to eating and satiety. Given their initial application in managing diabetes, the incretin-based therapies can lower blood sugar levels. Zepbound has demonstrated substantial weight reduction in overweight and obese individuals.
GLP-1 agonists have been around for a couple of decades, with the first-in-class Byetta (exenatide) receiving Food and Drug Administration (FDA) approval in 2005 to treat Type 2 Diabetes Mellitus (T2DM). Since then, multiple GLP-1 agonists have received FDA approval to manage T2DM. It wasn’t until 2014 that a GLP-1 first received FDA approval for weight loss—Saxenda (liraglutide). Thus began the trend of pharmaceutical companies repurposing the active ingredient of GLP-1s marketed under one brand name for management of T2DM into a different brand name for weight loss, as liraglutide for management of T2DM had been available as branded Victoza.. Aside from efficacy, other considerations for individuals include cost to the patient, contraindications, other concomitant health conditions, side effects, and patient preference. Incretin-based therapies should be avoided during pregnancy and are contraindicated in those with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B because some studies found a possible increased risk of thyroid cancer with the use of GLP-1 receptor agonists. Selection is often dependent on efficacy, contraindications, and adverse effects.
Compare Zepbound alternatives | |||
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Drug name | Price without insurance | SingleCare price | Savings options |
Zepbound (tirzepatide) | $1,524 per 4, 0.5 mL of 5 mg/0.5 mL pens | $945 per 4, 0.5 mL of 5 mg/0.5 mL pens | See latest prices |
Wegovy (semaglutide) | $1,825 per 4, 0.75 mL of 2.4 mg/0.75 mL pens | $1,225 per 4, 0.75 mL of 2.4 mg/0.75 mL pens | See latest prices |
Saxenda (liraglutide) | $1,805 per 5, 3 mL of 18 mg/3 mL pens | $1,214 per 5, 3 mL of 18 mg/3 mL pens | See latest prices |
Qsymia (phentermine/topiramate extended-release | $277 per 30, 7.5 mg/46 mg capsules | $80 per 30, 7.5 mg/46 mg capsules | See latest prices |
Contrave (naltrexone/bupropion) | $841 per 120, 8 mg/90 mg capsules | $635 per 120,8 mg/90 mg capsules | See latest prices |
Xenical, Alli (orlistat) | $925 per 90, 120 mg capsules | $631 per 90, 120 mg capsules | See latest prices |
Top 5 Zepbound alternatives
The following are some of the most common alternatives to Zepbound.
1. Wegovy (semaglutide)
While Zepbound is a dual receptor agonist of GIP and GLP-1, Wegovy only mimics GLP-1 and is referred to as a GLP-1 receptor agonist. Zepbound and Wegovy have similar efficacy for weight reduction and currently exhibit superior efficacy compared with all other medical weight-loss management options. Wegovy results in greater weight loss than Saxenda, as demonstrated in a network meta-analysis that demonstrated a more than 5% total weight loss more often in the Wegovy recipients—an average weight loss of 15.8 kg in the Wegovy arm versus 6.4 kg in the Saxenda arm, in a representative trial from the meta-analysis at 68 weeks.
Wegovy, like Zepound, offers a once-weekly subcutaneous injection administration. 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. Like the active ingredient tirzepatide is available as Zepbound for weight loss and Mounjaro for T2DM, Novo Nordisk’s semaglutide is also available as brand-name Wegovy for weight loss and Ozempic for T2DM.
2. Saxenda (liraglutide)
Saxenda is another GLP-1 receptor agonist whose active ingredient has been repurposed from Victoza. It is a brand-name version of liraglutide, approved for the treatment of T2DM. Saxenda represents the first GLP-1 receptor agonist FDA-approved for the treatment of obesity. Its dosing differs from the weekly administration of Zepbound and Wegovy and requires a once-daily subcutaneous injection. The maximum dose of 3 mg achieves optimal weight loss but is reached through a dose titration starting from 0.6 mg subcutaneously once daily, increased weekly. In a 56-week clinical trial comparing Saxenda 3 mg once daily versus a placebo injection, the average weight loss was significantly greater in the Saxenda group, achieving an average weight loss of 8 kg, versus 2.6 kg with placebo. Saxenda is a reasonable alternative option for individuals with T2DM who cannot access Zepbound or Wegovy. It also has demonstrated cardiovascular benefits in individuals with T2DM or who are at high risk of cardiovascular disease.
3. Qsymia (phentermine-topiramate)
Qsymia combines phentermine with an extended-release formulation of topiramate. This is an alternative to Zepbound in individuals without certain health conditions like cardiovascular disease or uncontrolled hypertension. Qsymia is the next-best alternative to incretin-based therapies as it has demonstrated strong efficacy in achieving weight loss. 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. Qsymia has also demonstrated sustained results, with an average total weight loss of 9.6 kg with the low dose and 10.9 kg with the high dose at 108 weeks of therapy.
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. Qsymia may also be preferred in patients for other reasons, such as those who experience migraines since topiramate is effective for migraine prophylaxis. Individuals receiving Qsymia should undergo regular blood pressure and heart rate monitoring.
Patients should also be informed of the possibility of neuropsychiatric side effects, including the risk of depression and suicidal thoughts. Qsymia is contraindicated during pregnancy due to the increased risk of birth defects when exposed during the first trimester of pregnancy, and is also contraindicated in patients with hyperthyroidism and glaucoma.
4. Contrave (naltrexone-bupropion)
Contrave combines naltrexone with bupropion. 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. This medication must be avoided in individuals with a seizure disorder, an eating disorder, or if an individual is using other bupropion-containing products. In addition, chronic opioid users should avoid this medication, as well as patients at risk of alcohol withdrawal due to the bupropion component, which may reduce the seizure threshold.
Contrave, like most weight-loss medications, does require a dose titration upon initiation. To start, the dose is one tablet (naltrexone 8 mg/bupropion 90 mg) once daily in the morning for 1 week. Patients can then increase the dose as tolerated in weekly intervals as follows: 1 tablet twice daily for 1 week; then, 2 tablets in the morning and 1 tablet in the evening for 1 week; then 2 tablets twice daily. If weight loss is below 4 to 5% of baseline, discontinuation of the medication is then recommended. Because Contrave includes bupropion, an antidepressant, discontinuation should occur slowly when therapy has exceeded 4 weeks, by tapering the dose over 2 to 4 weeks to allow for detection of symptoms masked by the medication. When compared to GLP-1 drugs, Contrave was associated with a lower incidence of side effects like pancreatitis, bowel obstruction, and gastroparesis.
5. Xenical (orlistat)
Xenical is an additional second-line therapy for chronic weight management, but its use is limited by lower efficacy than other therapies, as well as limited tolerability due to GI side effects. Xenical’s active ingredient, orlistat, works by changing fat digestion through the inhibition of pancreatic lipases. In turn, this increases fecal fat excretion because fat is essentially not changed to a form that can be absorbed. Efficacy-wise, a meta-analysis showed that patients randomly assigned to Xenical plus behavioral intervention lost 5 to 10 kg compared with just 3 to 6 kg in the control group (placebo plus behavioral intervention) at one year.
Xenical may be used chronically, having demonstrated efficacy in weight loss for up to four years. It can also positively impact cardiovascular risk factors like diabetes, high blood pressure, and high cholesterol. The downsides of orlistat are its side effect profile: fecal incontinence, flatus with discharge, and oily spotting. However, it is easily accessible and even available over-the-counter (OTC) in a formulation known as Alli.
Natural alternatives to Zepbound
It is important to note that all medical weight loss options are recommended to be used in combination with comprehensive lifestyle changes, like a hypocaloric diet, coupled with a minimum of 150 minutes of physical activity per week.
Dietary adherence is known to be the primary contributor to weight loss, not the specific diet selected. Behavior modification therapy is another component of a weight loss journey, designed to help patients make more permanent changes in their eating behavior.
Unfortunately, there is no silver bullet to weight loss; it often takes time and dedication. Individuals should not succumb to strong marketing schemes for dietary supplements, as limited evidence supports their efficacy or safety. Always seek medical advice from a healthcare professional before initiating any new therapies, even if they’re available OTC.
How to switch to a Zepbound alternative
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. Communication between the patient and healthcare provider is critical during transition periods to assess side effects, the ability to increase the dose, and potential drug interactions with the alternative.
Choosing the right path for weight loss treatment
There is no one-size-fits-all weight loss journey, and the right path depends on multiple individual factors like comorbid health conditions, weight loss goals, willingness to adhere to long-term lifestyle modifications, and access to prescription medications, either through insurance or without. Prior attempts to weight loss and barriers to success should be discussed with a healthcare provider so they may be addressed, including any mental health challenges like an eating disorder, physical limitations to prevent adherence to an exercise regimen, or concerns regarding affordability and access to medication. A multifaceted approach should be designed, including not only evidence-based dietary plans and physical activity goals, but also behavioral support programs should be offered.
Medications should be considered if the patient has a BMI of 30 or greater, or 27 or greater with comorbidities. Other options may need to be reviewed, including surgical options, particularly in those individuals motivated for a permanent change and willing to commit to long-term follow-up or who have failed non-surgical approaches in the past. Either way, initiating 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.
- FDA approves first medication for obstructive sleep apnea, Food and Drug Administration (2024)
- Tirzepatide once weekly for the treatment of obesity, New England Journal of Medicine (2022)
- ZEPBOUND (tirzepatide) injection. United States prescribing information. Revised November 2023. U.S. Food and Drug Administration. (Accessed on September 15, 2024).
- GLP-1 receptor agonists and the risk of thyroid cancer, Diabetes Care (2023)
- Risk of gastrointestinal adverse effects associated with glucagon-like peptide-1 receptor agonists for weight loss, JAMA (2023)
- Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: a network meta-analysis of randomized clinical trials, Obesity Reviews (2023)
- Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial, JAMA (2022)
- Semaglutide and cardiovascular outcomes in patients with Type 2 diabetes, New England Journal of Medicine (2016)
- Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial, Nature Medicine (2024)
- A randomized, controlled trial of 3.0 mg of liraglutide in weight management, New England Journal of Medicine (2015)
- Liraglutide and cardiovascular outcomes in Type 2 Diabetes, New England Journal of Medicine (2016)
- Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial, Lancet (2011)
- Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): A randomized, placebo-controlled, phase 3 extension study, The American Journal of Clinical Nutrition (2011)
- Effectiveness of primary care-relevant treatments for obesity in adults: A systematic evidence of review for the U.S. Preventative Services Task Force, Annals of Internal Medicine (2011)
- XENical in the prevention of diabetes in obese subjects (XENDOS) study: A randomized study of orlistat as an adjunct to lifestyle changes for the prevention of Type 2 diabetes in obese patients, Diabetes Care (2004)
- Effect of orlistat in overweight and obese patients with Type 2 diabetes treated with metformin, Diabetes Care (2002)
- Long-term effects of weight-reducing drugs in people with hypertension, The Cochrane Database of Systemic Reviews (2016)
- The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia, European Journal of Clinical Pharmacology (1994)
- Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: A randomized trial, JAMA (2005)
- Switching between glucagon-like peptide-1 receptor agonists: Rationale and practical guidance, Clinical Diabetes (2020)