Plenity vs Contrave Weight Loss Pills: Which Works Best?

When it comes to weight management, individuals often explore various options to support their journey toward a healthier body weight. From lifestyle changes and nutrition plans to medical interventions, the tools available to help people lose weight continue to evolve. Among the many options, prescription weight loss medications have gained popularity for their ability to assist with long-term weight reduction for certain individuals when combined with a healthy diet and regular exercise.

Two notable weight loss drugs that are often compared are Plenity and Contrave. Though both are approved for chronic weight management, they work in very different ways and are suited to varying types of individuals. This article provides an objective, evidence-based comparison of Plenity vs. Contrave weight loss pills, examining how each medication works, its effectiveness, potential side effects, and which patients may benefit most from its use.

Key Takeaways

• Mechanisms Differ: Plenity functions as a medical device that expands in the stomach to promote fullness, while Contrave combines two medications to influence appetite and cravings.​
• Efficacy Varies: Clinical studies suggest that both Plenity and Contrave can lead to significant weight loss when combined with lifestyle changes.​
• Considerations for Use: Both medications have specific contraindications and potential side effects that should be discussed with a healthcare provider.​

Plenity vs Contrave Comparison Table

Feature	Plenity	Contrave
Classification	Medical device	Prescription medication
FDA Approval Criteria	Adults with a BMI of 25–40 kg/m²	Adults with BMI ≥30, or ≥27 with weight-related conditions
Mechanism of Action	Expands in the stomach to promote fullness (non-systemic)	Alters brain chemistry to reduce appetite and cravings
Active Ingredients	Cellulose and citric acid	Bupropion (antidepressant) + Naltrexone (opioid antagonist)
Systemic Effects	None – not absorbed into the bloodstream	Yes – affects the central nervous system
Average Weight Loss	~5–10% of starting body weight over 24 weeks	~6–10% of starting body weight over 56 weeks
Common Side Effects	Bloating, flatulence, abdominal pain, constipation	Nausea, headache, dry mouth, insomnia, dizziness
Boxed Warning	No	Yes – increased risk of suicidal thoughts (due to bupropion)
Contraindications	Severe GI disorders, bowel obstruction, history of digestive diseases	Seizures, uncontrolled hypertension, current opioid use, and eating disorders
Drug Interactions	Minimal – not absorbed systemically	Multiple – interacts with CNS-active drugs and others
Best Suited For	Individuals seeking a non-drug, non-systemic aid for portion control	Individuals needing help with appetite regulation or emotional eating
Requires Lifestyle Changes	Yes – works best with diet and exercise	Yes – diet, exercise, and behavioral support are essential
Monitoring Requirements	Moderate – GI tolerance should be observed	High – requires regular monitoring for mental health and blood pressure
Prescription Required	Yes	Yes
Works Best When Combined With	Reduced calorie diet, hydration, and physical activity	Structured eating plan, therapy/support for cravings, physical activity

Understanding Plenity

What Is Plenity?

Plenity is a unique, FDA-approved medical device that functions as a weight loss pill — but it isn’t a traditional drug. It was approved to aid in weight management for a subset of adults with a body mass index (BMI) between 25 and 40 kg/m², which includes both overweight and obese individuals. Unlike many prescription weight loss medications that act on the brain or metabolic processes, Plenity works locally within the digestive system.

What sets Plenity apart is that it’s not a drug at all. Instead, it’s classified as a medical device because its active ingredients — cellulose and citric acid — are not absorbed into the bloodstream. Instead, they work within the gastrointestinal tract to help you feel full. This can make Plenity an appealing option for people seeking weight loss drugs with a lower risk of systemic side effects.

“Plenity represents a novel approach to treating overweight and obesity. By using non-systemic ingredients, we reduce many of the risks associated with traditional prescription medications,” says Dr. Matthew Olesiak, Chief Medical Director at SANE MD.

This distinction means Plenity may benefit those not typically candidates for prescription weight loss drugs, making it an increasingly popular option among newer weight loss medications approved by the FDA.

How Does Plenity Work?

Plenity ingredients — a hydrogel formulation made of citric acid and cellulose, both of which are naturally occurring compounds — are encased in easy-to-swallow capsules.  After taking three capsules with water 20 to 30 minutes before lunch and dinner, the ingredients absorb water in the stomach, forming a gel-like substance. This hydrogel expands to occupy space in the stomach and small intestine, mimicking the volume and texture of solid food.

This expansion triggers stretch receptors in the stomach wall, sending signals to the brain that indicate fullness—a process similar to what happens when you eat a large meal. This makes it easier for users to eat smaller portions and adhere to a reduced-calorie diet, both key to long-term weight loss and weight management.

Notably, because Plenity works entirely in the digestive tract and is not absorbed, it does not interfere with the central nervous system, metabolism, or other prescription medications a person may be taking. It’s later excreted naturally through the body’s waste.

“One of the major advantages of Plenity is that it helps people feel fuller with smaller meals, without any pharmacological impact,” says Dr. Olesiak. “This makes it a useful tool when paired with diet and exercise, especially for people who prefer a non-stimulant option.”

This mechanism allows Plenity to support chronic weight management in individuals who may not meet the higher BMI requirements typically needed for other anti obesity medications.

Efficacy of Plenity

​According to a 24-week randomized controlled trial published in Obesity, when used as directed and paired with lifestyle changes like a healthy diet and physical activity, Plenity can support clinically meaningful weight loss. In this study, 59% of participants using Plenity lost at least 5% of their starting body weight, and 27% achieved a weight loss of 10% or more. These results were significantly better than those in the placebo group, where only 42% reached the 5% threshold, and 15% reached 10%.

This level of weight reduction can offer substantial improvements in weight-related health conditions, including high blood pressure, type 2 diabetes, and elevated cholesterol. While not all users experience dramatic results, Plenity’s safety profile and tolerability make it an appealing option for long-term obesity treatment strategies.

It’s also worth noting that Plenity works best when used consistently, in conjunction with diet and exercise, and under the supervision of a healthcare provider familiar with weight loss medications.

Side Effects and Considerations

At this point, you might be asking, “Is Plenity safe?” Here’s the answer: Plenity is generally well-tolerated, especially compared to prescription weight loss pills that affect the central nervous system. Since Plenity is not absorbed into the bloodstream, it avoids many of the risks associated with traditional prescription drugs used to treat obesity or depression, such as increased blood pressure, insomnia, or mood changes.

The most commonly reported Plenity side effects include:

• Abdominal pain
• Bloating
• Flatulence
• Constipation

These symptoms are typically mild to moderate and often diminish with continued use as the digestive system adapts. Still, users with a history of digestive and kidney diseases should consult their healthcare provider before starting Plenity.

Plenity is also not recommended for individuals with severe gastrointestinal conditions such as bowel obstruction or Crohn’s disease. Because it is not suitable for everyone, a comprehensive medical evaluation is necessary before starting treatment — especially if you take other medications that could interact with digestion or hydration levels.

Despite its mild side effect profile, Plenity is not a magic bullet. For best results, it should be combined with lifestyle changes and a healthy eating plan to prevent weight regain and improve overall health problems related to excess weight.

Understanding Contrave

What Is Contrave?

Contrave is a prescription-only weight loss medication approved by the FDA for compatible adults with a body mass index (BMI) of 30 or higher, or 27 or higher with weight-related conditions such as high blood pressure or type 2 diabetes. It combines two active ingredients: bupropion, an antidepressant and smoking cessation aid, and naltrexone, a medication commonly used to treat alcohol or opioid dependence.

Together, these components target parts of the brain that influence appetite, hunger cues, and reward-driven eating behavior. By acting on these systems, Contrave helps reduce both physical hunger and emotional cravings, which can be key factors in weight gain for many individuals.

“Contrave’s dual mechanism targets the neurological drivers of overeating, particularly useful for patients struggling with emotional or habitual eating,” explains Dr. Matthew Olesiak, Chief Medical Director at SANE MD.

How Does Contrave Work?

Contrave works by modifying brain signals related to hunger and food cravings. Bupropion boosts dopamine and norepinephrine levels—neurotransmitters that affect mood and appetite suppression—while naltrexone modulates the brain’s reward system, making food less appealing during times of stress or emotional distress.

This combination not only reduces the desire to eat but also curbs the sense of gratification from food, which is particularly helpful for individuals who tend to overeat in response to emotions, fatigue, or habit. The treatment plan typically involves a gradual dose escalation over several weeks to help the body adjust and minimize side effects.

Contrave is intended for long-term use in conjunction with a reduced-calorie diet and increased physical activity. It is not a quick-fix pill, and sustained results depend on consistency and support from healthcare professionals.

Efficacy of Contrave

In a phase 3 study published in Obesity, participants who took Contrave lost an average of 6.4% of their starting body weight over 56 weeks, compared to just 1.2% in the placebo group.

Additionally, patients on Contrave were more likely to experience improvements in blood sugar, cholesterol, and blood pressure, especially if they had obesity-related metabolic conditions. However, weight loss results can vary widely depending on adherence, dosage titration, and the presence of side effects.

Side Effects and Considerations

Contrave affects the central nervous system, which means it carries a higher risk of side effects than non-systemic options like Plenity.

Common side effects include:

• Nausea
• Headache
• Dry mouth
• Insomnia
• Dizziness

More seriously, Contrave carries a boxed warning for increased risk of suicidal thoughts and behaviors, particularly in younger adults, due to the bupropion component. It should not be used by individuals with a history of seizures, uncontrolled hypertension, or those currently taking opioids or undergoing alcohol withdrawal.

Because of its effects on mood and blood pressure, regular monitoring is essential—especially in the first few months of use. A full medical history should be reviewed to assess for possible contraindications, drug interactions, or risks of adverse psychological effects.

Comparing Plenity and Contrave

When choosing between Plenity and Contrave, it’s essential to look beyond brand names and understand how these weight loss medications actually work, how effective they are, and which individuals they best serve.

Though both fall under the umbrella of prescription weight loss aids, their differences are significant in terms of how they help people lose weight, how they impact the body, and what kind of support and monitoring they require.

Mechanism of Action

Plenity and Contrave approach weight loss in fundamentally different ways.

Plenity works mechanically, not chemically. It expands in the stomach and small intestine after ingestion, physically occupying space and signaling satiety (fullness) to the brain. It does not alter brain chemistry or hormonal signals. Because it is not absorbed into the bloodstream, Plenity avoids systemic interactions with other prescription medications, making it a non-invasive tool for weight management.

In contrast, Contrave is a combination of bupropion and naltrexone, two prescription drugs that directly affect the brain. Bupropion, originally developed to treat depression and aid smoking cessation, boosts dopamine and norepinephrine activity, helping reduce appetite. Naltrexone, often used to treat alcohol and opioid dependence, reduces food cravings by acting on the brain’s reward center. Together, these agents help reduce the emotional and neurological drive to eat — a significant contributor to weight gain and overeating for many people.

Plenity can be taken by individuals looking for weight loss pills that don’t alter mood, cognition, or cardiovascular activity, while Contrave’s central nervous system effects make it better suited for those needing help with behavioral and emotional aspects of weight loss.

Efficacy

Both Plenity and Contrave are supported by clinical trials showing that, when used with lifestyle changes, they can help certain individuals lose weight and maintain those results.

Plenity’s results show that more than half of users experience a 5% reduction in body weight over 24 weeks. While its total average weight loss may be more modest than Contrave, it offers a gradual, steady reduction with a lower risk profile.

According to a randomized, phase 3 trial published in Obesity, Contrave has demonstrated significant weight reduction in some trials. Specifically, in a 56-week study, participants receiving Contrave experienced an average weight loss of 6.4% of their body weight, compared to 1.2% in the placebo group. However, this comes with more frequent and potentially more severe side effects, which may limit its use in some individuals.

The effectiveness of both weight loss medications also depends on adherence. Users who consistently pair the medicines with a reduced-calorie diet, exercise, and healthy habits are more likely to see meaningful and lasting weight changes. Neither pill works in isolation.

Safety Profiles

When it comes to safety, the contrast between Plenity and Contrave becomes clearer.

Plenity is well tolerated for most users. Because it acts within the gastrointestinal tract, side effects are generally limited to abdominal pain, bloating, flatulence, and constipation. It does not increase blood pressure or cause mood changes, and it avoids interactions with other medications. However, it is not recommended for individuals with digestive and kidney diseases, and those with specific rare genetic disorders affecting digestion should avoid it.

Contrave, on the other hand, carries a black box warning due to its bupropion component, which has been linked to an increased risk of suicidal thoughts in young adults. It is contraindicated in people with seizure disorders, uncontrolled hypertension, or those on opioids or undergoing withdrawal from alcohol. Common side effects include nausea, headache, dry mouth, insomnia, and dizziness.

Additionally, Contrave may cause elevated blood pressure, making it unsuitable for those with high blood pressure or heart-related conditions. There’s also a risk of severe liver injury, particularly in those with pre-existing liver conditions or those taking other hepatotoxic drugs.

Because of these differences, anyone considering Contrave must undergo a detailed evaluation of their personal or family history of mental health, seizures, and cardiovascular conditions.

Suitability for Different Individuals

Determining which weight loss pill is better — Plenity or Contrave — requires a personalized approach. The right choice depends on your medical history, lifestyle preferences, risk tolerance, and how much weight loss you’re aiming for.

• Plenity is ideal for:
  • Adults with a BMI between 25–40 kg/m² looking for a non-systemic solution
  • People who want a medication that doesn’t affect the brain or heart
  • Those with concerns about drug interactions or side effects from prescription medications
  • Users who prefer a tool that aids with portion control and encourages healthier eating patterns
• Contrave may be a better option for:
  • Individuals struggling with emotional eating or intense food cravings
  • Those with obesity-related conditions like type 2 diabetes, high blood pressure, or high cholesterol
  • Adults who haven’t had success with other weight loss medications
  • Patients under the care of a healthcare provider trained in obesity medicine or psychiatry who can monitor for adverse mental health effects

Notably, both drugs are meant to be part of a broader strategy involving lifestyle changes, diet, exercise, and behavioral support. Neither replaces the foundational principles of obesity treatment, but both can be helpful tools on the path to a healthy weight.

How to Enhance the Effects of Plenity or Contrave

While both Plenity and Contrave can support weight loss, their success largely depends on how well they’re integrated into a broader, sustainable routine. Neither medication is a substitute for lifestyle changes, but when combined with healthy habits, they can help individuals lose weight more effectively and maintain those results long term.

Below are evidence-based strategies that may promote weight loss and improve outcomes when taking either medication.

1. Follow a Healthy, Balanced Diet

One of the most important ways to maximize the effects of any weight loss pill is to follow a healthy eating plan.

Whether you’re using Plenity to feel fuller with fewer calories, or Contrave to reduce cravings, focusing on whole foods will help:

• Prioritize lean proteins, vegetables, high-fiber carbohydrates, and healthy fats.
• Avoid ultra-processed foods high in sugar and refined grains, which may lead to weight gain.
• Stick to a reduced-calorie diet as recommended by your healthcare provider.
• Consider meal prepping to avoid impulsive eating, and track intake with an app or food diary.

This not only helps reduce body fat but also supports stable blood sugar and blood pressure levels.

2. Engage in Regular Physical Activity

Pairing weight loss medications with physical activity has been shown to significantly increase the odds of sustained weight reduction. Movement improves metabolism, preserves muscle mass, and enhances overall health.

• Aim for at least 150 minutes of moderate-intensity exercise per week (e.g., brisk walking, cycling, swimming).
• Include strength training 2–3 times weekly to increase muscle mass and support long-term weight management.
• Start slow if you’re sedentary — even short walks after meals can support digestion and curb cravings.

If you’re unsure where to begin, consult a trainer or physical therapist familiar with chronic weight management programs.

3. Prioritize Restful Sleep

Sleep plays a surprisingly important role in weight management. Research shows that insufficient or poor-quality sleep can disrupt hormones that control hunger and satiety, making it harder for people to lose weight.

• Aim for 7–9 hours of uninterrupted sleep per night.
• Avoid screens an hour before bed to improve melatonin production.
• Create a bedtime routine that promotes relaxation, such as journaling or meditation.

Poor sleep may also increase stress levels, which can trigger emotional eating — a challenge especially relevant for Contrave users working to control cravings.

4. Manage Stress and Emotional Eating

Stress is a common trigger for weight gain, especially through binge eating or snacking on high-calorie comfort foods. Contrave may help reduce food-related cravings, but it’s still important to develop stress-management techniques:

• Practice mindfulness, meditation, or yoga.
• Seek behavioral counseling or therapy if emotional eating is frequent.
• Join a weight loss support group or work with a health coach for accountability.

Addressing mental health and emotional patterns can make weight loss medications significantly more effective.

5. Stay Consistent with Medication and Medical Check-Ins

Whether you’re taking Plenity or Contrave, prescription weight loss drugs are most effective when used exactly as prescribed.

• Take your doses at the same time each day (Plenity before meals, Contrave as directed).
• Monitor any side effects, especially abdominal pain, nausea, or changes in blood pressure.
• Schedule regular follow-ups to assess progress and adjust dosage if needed.
• Ask your doctor about alternative weight management medications or options if you’re not seeing results after 12–16 weeks.

Being consistent with your medication and medical appointments is just as important as diet and exercise in the overall success of your treatment.

Frequently Asked Questions (FAQ)

If you’re researching Plenity vs Contrave weight loss pills, it’s natural to have questions about how they compare to other prescription weight loss medications, how quickly they work, and what alternatives are available.

Below are answers to some of the most common questions to help you make an informed decision.

1. Is there a better weight loss drug than Contrave?

There may be more effective weight loss medications than Contrave for some individuals, depending on their medical history, goals, and response to treatment. Drugs like phentermine-topiramate (Qsymia) and semaglutide (Wegovy, Ozempic) have shown higher average weight loss in clinical trials and are considered among the top weight loss medications currently available. See our comprehensive guide to these and other Plenity alternatives.

However, these drugs also come with their own risks and side effects, and not everyone qualifies to take them. The “best” option varies based on individual health needs, cost, and access to care. It’s important to consult a healthcare provider or an obesity medicine specialist to determine the most appropriate treatment.

2. Does Plenity really work for weight loss?

Yes, Plenity has been shown in clinical studies to help people lose weight when used alongside lifestyle changes such as a reduced-calorie diet and exercise. While its weight loss results may be more modest compared to other prescription weight loss drugs, many users find it helpful for reducing hunger and portion sizes.

Because it works as a medical device and is not absorbed into the bloodstream, Plenity tends to have fewer systemic side effects. It’s especially suitable for people who want to avoid stimulant-based medications or who fall into the overweight (not obese) BMI range. As with all weight loss pills, consistent use and dietary habits are key to success.

3. How fast will I lose weight on Contrave?

Most people start noticing some weight loss within the first 4 to 8 weeks of using Contrave, especially when combined with diet and exercise. In clinical trials, users lost about 6% of their body weight on average after one year, though results vary widely depending on adherence and metabolism. It’s important to note that Contrave is designed for chronic weight management, not rapid weight reduction.

Patients who do not lose at least 5% of their starting body weight after 12 weeks may be advised to discontinue the medication. Regular follow-ups with your doctor are essential to evaluate progress and manage side effects.

4. What is the most effective oral weight-loss medication?

Among oral prescription weight loss medications, phentermine-topiramate (Qsymia) is currently considered one of the most effective. Clinical studies have shown significant reductions in body weight compared to other weight loss drugs, with some users losing over 10% of their starting body weight. It works by suppressing appetite and increasing feelings of fullness.

However, it also comes with potential risks, such as increased blood pressure, birth defects, and mood changes, so it requires close medical supervision. Other options, like Contrave or Orlistat, may be better tolerated, depending on the individual.

5. What can I replace Contrave with?

If you’re looking for an alternative to Contrave, you might consider several prescription weight loss pills or anti-obesity medications, depending on your health needs. Options include Plenity, which helps promote fullness without affecting brain chemistry; phentermine-topiramate, which is highly effective but more tightly regulated; and GLP-1 receptor agonists like Wegovy or Saxenda, though these are injectable medications.

If medications are not suitable, your doctor may also recommend a combination of lifestyle changes and behavioral therapy. Always discuss any switch in treatment with a licensed healthcare provider to ensure safety and effectiveness.

Conclusion

Choosing between Plenity vs Contrave weight loss pills ultimately depends on your personal health history, weight loss goals, and lifestyle. Both are FDA-approved and effective when used as part of a comprehensive plan that includes lifestyle changes, a healthy diet, and regular exercise.

Whether you’re looking for a non-systemic medical device like Plenity or a central-acting prescription weight loss drug like Contrave, the key is working closely with your healthcare provider to find the safest, most effective solution for your needs.

With the proper support and consistency, both medications can play an important role in helping you reach a healthy weight and improve your overall well-being.

References

Clinical Diabetes

Obesity

Obesity