Can’t Take GLP-1s? Here are 4 GLP-1 Alternatives for Weight Loss to Consider

Glucagon-like peptide-1 (GLP-1) medications like Wegovy (semaglutide) and Zepbound (tirzepatide) have gained popularity for their ability to help people lose weight. But they’re not the best option for everyone. Some people may not tolerate the side effects. And medical conditions, such as a history of certain thyroid cancers, can make GLP-1s unsafe to take.

If you can’t take GLP-1s, there are several other FDA-approved weight-loss medications to consider. Here’s what you should know about four GLP-1 alternatives.

1. Qsymia

Qsymia is a once-daily weight-loss pill containing two active ingredients: phentermine and topiramate. Phentermine is a stimulant that lessens appetite and increases energy expenditure. Topiramate (Topamax) is thought to affect hunger, appetite, and food cravings.

Qsymia is approved for people ages 12 and older with a larger body size. During initial clinical trials, most people taking Qsymia lost at least 5% of their starting body weight after 1 year. About half of those in the trial lost at least 10% of their starting body weight during this time.

Compared to GLP-1 medications, Qsymia has different side effects and risks. Examples include dry mouth, taste changes, and numbness or tingling of the hands, arms, feet, or face. Since it’s a controlled substance, Qsymia also has a risk of dependency and misuse. And if you take other medications, your healthcare team will need to screen for potential interactions.

Qsymia may be an effective weight-loss option for many people, but it isn’t suitable for everyone. For example, it’s recommended to avoid taking Qsymia if you have glaucoma.

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How to save on Qsymia

Qsymia is currently available as a brand-name medication. The FDA has approved a generic version, but it isn’t available yet. There are ways to save on Qsymia, including:

• Save with GoodRx: Anyone with a valid prescription, regardless of insurance status, can use GoodRx to buy a 30-day supply of Qsymia at an exclusive cash price of $149.10.

• Save with a copay savings card: If you have commercial insurance, you may be eligible to pay as little as $70 for Qsymia using a savings card from the manufacturer. A home-delivery program called Qsymia Engage is also available.

2. Contrave

Contrave (bupropion / naltrexone) is a combination weight-loss pill approved for adults who meet certain body mass index criteria. The first ingredient, bupropion, is an antidepressant that affects dopamine levels to reduce appetite and food cravings. Naltrexone is an opioid blocker that helps prolong bupropion’s effects.

Contrave is taken twice daily (after the first week) and can be especially helpful for people who experience emotional eating. Clinical trials showed that after about 1 year:

• About 40% of people taking Contrave lost at least 5% of their starting body weight.

• Over 20% lost at least 10% of their starting body weight.

• Weight loss was even greater when Contrave was combined with a program consisting of diet, exercise, and behavioral therapy.

Similar to GLP-1s, people taking Contrave report side effects such as nausea and vomiting, stomach pain, and constipation. But it can also cause dry mouth, anxiety, and excess sweating. Increased blood pressure and heart rate are also possible. Contrave can also interact with a number of medications.

Contrave can be an effective addition to a weight-loss plan, but it may not be right for everyone. For example, it’s recommended to avoid taking Contrave if you have unmanaged high blood pressure or are currently taking opioids or undergoing opioid withdrawal.

How to save on Contrave

Contrave is currently available as a brand-name medication. There are ways to save on Contrave to help make your prescription more affordable:

• Save with a copay savings card. If you have commercial insurance, you may be eligible to pay as little as $20 per month for Contrave using a savings card from the manufacturer.

• Save with a patient support program. Pay $99 or less for Contrave through the CurAccess Program.

3. Orlistat

Orlistat (Alli, Xenical) is an oral lipase inhibitor, meaning that it blocks fat absorption in the digestive tract. After taking a dose, it prevents about 25% of the fat you eat from being absorbed. Unlike other weight-loss medications that act on the brain to affect appetite, orlistat works directly in the gut.

Orlistat is available OTC (Alli) for adults and with a prescription (Xenical) for people ages 12 and older. Both forms are taken 3 times a day with meals containing fat. But the prescription dose (180 mg) is 3 times higher than the OTC dose (60 mg). And in addition to helping with weight loss, Xenical can also lower the risk of regaining weight from prior weight loss.

During initial clinical trials, over half of people taking Xenical lost at least 5% of their starting body weight after 1 year. Since the dose is lower, Alli is slightly less effective than Xenical. But some people may find the lower dose easier to tolerate. For best results, orlistat should be paired with a low-fat diet (30% of calories from fat or less).

GLP-1 medications are commonly associated with gastrointestinal side effects such as stomach pain and diarrhea. Orlistat can also cause unpleasant digestive issues, including loose stools, oily stools, and gas with oily spotting. And because of how orlistat works, it may interact with certain medications.

Orlistat may not be safe for everyone, especially people with certain medical conditions or dietary needs. For example, it’s recommended to avoid taking orlistat if you have cholestasis (slowed or stopped bile flow from the liver).

How to save on orlistat

There are ways to save on OTC and prescription orlistat. Alli and Xenical are both available as brand-name medications. But a Xenical authorized generic is also available, which is the same as Xenical but without the brand name on the label. Here are ways to make your medication more affordable:

• Save with GoodRx. After getting a prescription from a healthcare professional, pay as little as $50.69 for Alli at certain pharmacies with a GoodRx discount. The price of brand-name Xenical is as low as $433.85.

• Save with the authorized generic. The price of the Xenical authorized generic is as low as $556.91 with GoodRx.

• Save with a coupon from the manufacturer. If you're buying Alli without a prescription, the manufacturer has a coupon available, which you can have emailed to you. Just present it at the register when you’re ready to buy.

4. Phentermine

Phentermine is a stimulant medication that has been used for weight loss for decades. As mentioned, it’s one of the active ingredients in Qsymia. But it’s also available on its own for people ages 17 and older under the brand names Adipex-P and Lomaira. Adipex-P is taken once daily, while Lomaira is a lower-dose version that’s taken 3 times daily before meals.

Unlike the other weight-loss medications on this list, phentermine is only approved for short-term use — up to 12 weeks (3 months). This is because there was limited long-term safety data when it was first approved. Since then, more recent evidence suggests that it may be safe and effective beyond 3 months. However, some people develop a tolerance to phentermine, meaning that it doesn’t work as well over time.

Phentermine’s stimulant effects can help lessen appetite. But they can also cause unique side effects. Examples include tremor (shakiness), trouble sleeping, and increased heart rate and blood pressure. Like Qsymia, phentermine is a controlled substance with a risk of dependency and misuse. It can also interact with other medications and substances.

Like the other medications on this list, phentermine may not be safe for everyone. For example, it’s recommended to avoid taking phentermine if you have a history of heart disease or unmanaged high blood pressure.

How to save on phentermine

Phentermine is available as brand-name and generic medications. For many people, it can be a more affordable option. With a GoodRx discount, you could pay as little as $13.80 for generic phentermine tablets. Lomaira, which is brand name only, costs as little as $47.44 with GoodRx. A manufacturer copay card is also available.

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How to choose the best option for you

The best weight-loss medication depends on your health history, lifestyle, and weight-loss goals. Here are a few factors to consider when choosing an alternative to GLP-1 medications:

• Health conditions: Some GLP-1 alternatives may not be safe to take if you have certain health conditions, such as heart disease. Your healthcare team will review your health history to recommend options that are safest for you.

• Interactions: Certain medications can interact with weight-loss drugs. Make sure your healthcare team has your current medication list to check for potential interactions.

• Treatment goals: If emotional eating is a concern, Contrave may be a good option to consider. Or if you’ve previously lost weight, Xenical can help lower the risk of regaining the weight you’ve lost.

• Lifestyle factors: Medications like orlistat work best if you can stick with a low-fat diet. If you continue eating high-fat foods, you may be more likely to experience side effects.

• Short-term vs. long-term: Phentermine is approved for short-term use, while Qsymia, Contrave, and orlistat can help with weight management more long term.

Ultimately, your healthcare team can help determine the best medication for you based on these and other factors.

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Written by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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