Contrave vs. Zepbound for weight loss

Zepbound (tirzepatide) and Contrave (naltrexone and bupropion) are two weight loss medications. Zepbound is a weekly injection, while Contrave is a daily pill, but those are not the only differences between the two. Read on as we review the key differences between Contrave vs. Zepbound for weight loss.

Here’s an overview of how Contrave and Zepbound compare:

Contrave and Zepbound work differently in the body to produce weight loss.

Contrave is a combination of two active ingredients — naltrexone and bupropion — which work together in the central nervous system to:

• Reduce the amount of reward you get from eating

• Limit how hungry you feel when you encounter certain triggers, such as thinking about food, feeling stressed, or seeing an ad for your favorite restaurant

• Enhance your self-control

Naltrexone blocks opioid receptors in the brain, so you feel less reward after eating food. Bupropion increases the levels of dopamine and norepinephrine, two transmitters that reduce hunger. Together, these effects help suppress your appetite and disordered eating behaviors, including emotional or binge eating.

Zepbound has a single active ingredient: tirzepatide. It is a peptide that works by mimicking two hormones produced naturally by the body. These hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Zepbound works by activating these hormones' receptors throughout the body, which:

• Slows down how quickly food leaves your stomach

• Regulates your blood sugar levels after you eat

• Sends satiety (fullness) signals to your brain

• Helps your body burn fat more efficiently

Together, these effects help you feel full sooner, stay full longer, and experience fewer cravings and "food noise."

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Contrave and Zepbound are both approved by the US Food and Drug Administration (FDA) for weight loss and chronic weight management. Zepbound is also approved to treat moderate-to-severe obstructive sleep apnea (OSA).

Contrave is FDA-approved to:

• Reduce excess body weight and maintain long-term weight reduction in:

  • Adults with obesity 

  • Adults with overweight plus at least one weight-related medical condition, such as high blood pressure, type 2 diabetes, or high cholesterol

Zepbound is FDA-approved to:

• Reduce excess body weight and maintain long-term weight reduction in:

  • Adults with obesity 

  • Adults with overweight plus at least one weight-related medical condition, such as high blood pressure, type 2 diabetes, or high cholesterol

• Treat moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity

Both Contrave and Zepbound are intended to be used with lifestyle changes such as an eating plan and exercise.

While Contrave and Zepbound have not been compared directly, separate clinical studies show Zepbound may be better for weight loss than Contrave. In general, Zepbound is considered one of the most effective weight loss medications available today.

Contrave 

In clinical trials, people lost 5–8% of their body weight in one year. When combined with intensive lifestyle changes — and visits with dietitians, physical trainers, and therapists — just over half (55%) of people taking Contrave lost at least 10% of their body weight. In general, people are expected to lose at least 5% within the first 12 weeks of taking Contrave.

Zepbound

In clinical trials, people lost 15%–21% of their body weight in 72 weeks. Those taking higher doses lost more weight. As many as 83% of people lost at least 10% of their body weight, and up to 57% lost at least 20%. In general, people lose at least 8% of their body weight within the first 12 weeks of taking Zepbound.

In short, while the two have not been compared directly, separate studies show that people lose significantly more weight on Zepbound than on Contrave.

Contrave is a twice-daily pill while Zepbound is a once-weekly injection.

Contrave

Contrave is an oral tablet that is typically taken twice per day, once in the morning and once in the evening.

How to take it: Contrave tablets should be swallowed whole (i.e. never crushed, split, or chewed). Avoid taking Contrave with high-fat meals, as it may increase the risk of serious side effects, including seizures.

Doses: Contrave extended-release tablets come in a single dosage strength. Each tablet contains 8 mg of naltrexone and 90 mg of bupropion.

Dosing: Contrave follows a dosage escalation schedule. You will start low and work your way up to the recommended maintenance dosage according to a schedule that looks like this:

• Week 1: One tablet in the morning

• Week 2: One tablet in the morning and one tablet in the evening

• Week 3: Two tablets in the morning and one tablet in the evening

• Week 4+: Two tablets in the morning and two tablets in the evening

Zepbound 

Zepbound is a weekly injection that is taken on the same day each week, at any time of day.

How to take it: Inject Zepbound on the same day each week at any time of day, regardless of when you last ate. Rotate injection sites (possible injection sites include the thigh, abdomen, and upper arm) with each injection.

Doses: Zepbound comes in six dosage strengths: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg. It comes in single-dose pens or vials, and multi-dose KwikPens.

Dosing: Zepbound typically begins at a low 2.5 mg dose, and then increases at least every four weeks until you reach a maintenance dose that produces weight loss with manageable or minimal side effects. A typical Zepbound dose escalation schedule looks like this:

• Weeks 1–4: 2.5 mg weekly

• Weeks 5–8: 5 mg weekly

• Weeks 9–12: Stay at 5 mg weekly or increase to 7.5 mg weekly

• Weeks 13–16: Stay at previous dosage or increase to 10 mg weekly

• Weeks 17–20: Stay at previous dosage or increase to 12.5 mg weekly

• Weeks 21+: Stay at previous dosage or increase to 15 mg weekly 

While Contrave and Zepbound share some gastrointestinal side effects — including nausea, diarrhea, and vomiting — they have different side effect profiles since they work differently in the body.

Contrave side effects 

The most common side effects of Contrave include:

• Nausea

• Constipation

• Headache

• Vomiting

• Dizziness

• Insomnia

Contrave can also cause rare but serious side effects, including seizures, increased blood pressure and heart rate, and liver or vision problems. People with type 2 diabetes may have a higher risk of experiencing low blood sugar when taking Contrave. The medication also carries a boxed warning for suicidal thoughts and behaviors.

Zepbound side effects 

The most common side effects of Zepbound include:

• Nausea

• Diarrhea

• Vomiting

• Constipation

• Abdominal pain

• Upset stomach

In rare cases, Zepbound can cause serious side effects, including kidney or gallbladder problems, acute pancreatitis, and pulmonary aspiration during general anesthesia. In people with type 2 diabetes, Zepbound can increase the risk of low blood sugar (when used with insulin) and diabetes-related vision problems.

The cost of Contrave and Zepbound varies widely depending on your insurance coverage and the pharmacy you use. Neither Contrave nor Zepbound is available as a generic, so the only option is to get the more expensive brand-name version.

Contrave

Without insurance, Contrave costs $840 per month, on average. 

Insurance coverage: Contrave may or may not be covered by insurance. Some insurance plans are less likely to cover weight loss medications. 

Medicare Part D coverage: Medicare Part D does not cover traditional weight loss pills such as Contrave.

How to save: 

• For people with private insurance coverage for Contrave, the manufacturer savings card can make the cost of a monthly refill completely free.

• For people without insurance coverage for Contrave, the CurAccess prescription delivery program caps the cost of Contrave at $99 per month.

• Prescription discount cards — such as those offered for free by SingleCare or GoodRx — can lower the cost of Contrave by $230 per month.

Zepbound 

Without insurance, Zepbound costs $499–$1,086.37 per month.

Insurance coverage: Zepbound may or may not be covered by insurance. Some insurance plans are less likely to cover weight loss medications. Check if your plan covers Zepbound using Ro's free GLP-1 insurance checker.

Medicare Part D coverage: While Medicare does not typically cover weight loss medications, the temporary GLP-1 Bridge program includes coverage for Zepbound KwikPens, along with Foundayo (orforglipron) and Wegovy (semaglutide). The program is slated to end December 31, 2027. Until then, the monthly copay is $50. Medicare covers Zepbound for sleep apnea.

How to save: 

• Cash payers can get the Zepbound KwikPens on Ro for $299–$449 per month (limited-time offer; see more here).

• For people with private insurance coverage for Zepbound, the manufacturer savings card can lower the cost of Zepbound to as low as $25 for a one- or three-month refill.

• Pharmacy-specific Zepbound coupons — offered for free on sites such as SingleCare, GoodRx, or Optum Perks — can also lower the cost of a monthly refill.

While Contrave and Zepbound are safe for many people, they are not the right choice for everyone.

Who shouldn’t take Contrave?

You should not take Contrave if you:

• Are pregnant or breastfeeding

• Are under 18

• Have uncontrolled high blood pressure

• Have seizures

• Have an eating disorder, including anorexia or bulimia

• Have an allergy to naltrexone, bupropion, or any of the inactive ingredients

• Are in the process of quitting smoking, drinking, benzodiazepines, barbiturates, or antiseizure medications

You also should not take Contrave if you take any of the following medications:

• Other drugs that contain bupropion

• Opioids

• Monoamine oxidase inhibitors (MAOIs)

• CYP2B6 inducers, including ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin

• Levodopa

• Amantadine

If you take certain antidepressants or other medications, your healthcare provider may recommend adjusting the dosage of those medications if you are prescribed Contrave.

Who should not take Zepbound?

You should not take Zepbound if you:

• Are pregnant, breastfeeding, or planning to be

• Are under 18

• Have an allergy to tirzepatide or any of the inactive ingredients

• Have a personal or family history of certain thyroid cancers, including medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia type 2 (MEN2)

Both Contrave and Zepbound are considered safe and effective weight loss medications. The right choice for you will depend on your current health situation, weight loss goals, and personal preferences. Your healthcare provider can help you make the best decision. Here are some factors to consider in the meantime:

Contrave may be better if:

• You have a fear of needles or simply prefer an oral medication

• You like the routine of a daily medication

• Your insurance offers better coverage for Contrave

• You’re worried about experiencing side effects that are more common with Zepbound, such as abdominal pain or fatigue

Zepbound may be better if:

• You want larger weight loss results

• You like the convenience of a once-weekly injection

• You also have obstructive sleep apnea

• Your insurance offers better coverage for Zepbound, or you pay cash for your prescriptions

• You take other medications that interact with Contrave, or have other conditions that make it unsafe for you to take

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Zepbound and Contrave can both be safe and effective medications for weight loss. Your healthcare provider can help you determine which one is right for you depending on your goals, personal health history, and lifestyle.

• Zepbound is a weekly GLP-1/GIP injection that works by mimicking two hormones that slow digestion and boost fullness, while Contrave is a twice-daily oral appetite suppressant that works by targeting areas of the brain's reward center.

• Zepbound is one of the most effective weight loss medications currently available — producing more weight loss than Contrave, Wegovy, and other options.

• Both Contrave and Zepbound can cause digestive side effects, but Zepbound may produce more (including belching and heartburn) while Contrave can also cause insomnia and dry mouth.

• Both medications have unique contraindications that may make them unsafe for people with certain health conditions.

• Insurance coverage can vary for both Contrave and Zepbound, but there are several savings options, including manufacturer savings cards and cash-pay programs.