5 Best Weight Loss Pills: Pros, Cons, and How They Work

More than two-thirds of U.S. adults are considered overweight or obese, according to the Centers for Disease Control and Prevention (CDC). Because of the continued rise of obesity, there is a growing interest in weight loss pills.

But with so many options, knowing which are the best weight loss pills out there can be challenging.

We carefully selected five of the best weight loss pills to reduce the overwhelm. Factors we considered when choosing the best weight loss pills include:

• The quality of research available
• Average amount of weight loss achieved
• Risks and side effects
• FDA approval status
• Long-term safety and effectiveness of the product.

Here are our top five best weight loss pills — and how to use them most effectively. Always carefully discuss the potential benefits and risks of taking weight loss pills with your healthcare provider.

We chose these five weight loss pills because they contain research-backed ingredients for weight loss, have a good safety profile, and are FDA-approved.

While these pills may boost weight loss, they are most effective with a reduced-calorie diet and exercise regimen.

1. Phentermine (Adipex-P and Lomaira)

Phentermine is one of the most widely used prescription weight loss medications in the United States and has been around since the 1950s. It’s part of a class of drugs called anorectics, which research has shown suppress the appetite.

The U.S. Food and Drug Administration (FDA) has approved it for short-term use for up to 12 weeks.

How It Works

Research suggests phentermine works by blocking the release of norepinephrine, a neurotransmitter in the brain that makes you hungry. It’s taken as a 15, 30, or 37.5 milligram (mg) tablet before meals, where the dose starts low and is gradually increased according to your provider’s recommendations.

Who Is Eligible?

You qualify if you have a BMI of 30 or greater or a BMI of 27 with at least one coexisting weight condition such as diabetes and high blood pressure.

What the Research Says

Several studies demonstrate the ability of phentermine to induce weight loss.

A meta-analysis of six studies ranging from 2 to 24 weeks long found those taking 15–30 mg of phentermine per day had an average additional weight loss of 7.9 pounds (lb) compared with placebo.

In a more recent study comparing the effectiveness of various weight loss medications, researchers found that phentermine resulted in the most significant weight loss in 12 weeks, with an average loss of 8.3 lb.

Another study, published in 2021, showed that 40 percent of participants who took phentermine in either 15 or 30 mg doses lost at least 5 percent of their body weight in six months.

Most of the research done, however, is funded by the pharmaceutical industry, so there may be an element of bias in the study design.

Cost

Phentermine is often covered by insurance, depending on your insurance carrier. If not, the cost is $1 per pill or $42 per month.

Safety and Side Effects

The most common phentermine side effects include dry mouth, insomnia, nausea, sweating, irritability, constipation, headache, and nervousness, according to research.

While rare, more severe side effects include heart palpitations, increased blood pressure, kidney and vision problems, suicidal ideation, cognitive impairment, and electrolyte imbalances.

Phentermine is considered a stimulant and controlled substance, as it’s chemically similar to amphetamine, but research shows it has low potential for abuse.

RD Verdict

Phentermine can be an effective weight loss pill in the short term, but more research is needed on its safety and effectiveness for longer than six months.

2. Qsymia (Phentermine and Topiramate)

This popular weight loss pill contains phentermine combined with a migraine medication called topiramate. Research shows combining these two drugs may result in greater weight loss than either alone.

Qsymia is FDA-approved, available as a prescription only, and approved for long-term use.

How It Works

Phentermine and topiramate in Qsymia work together to alter neurotransmitter levels to decrease appetite and cravings, according to research. It may also alter the taste of certain foods to make them less desirable.

Qsymia is taken once daily in the morning. Doses start low at 3.75 mg to 23 mg and gradually increase to 15 mg to 92 mg as tolerated.

Who Is Eligible?

You’re eligible with a BMI of 30 or greater or a BMI of 27 or more with at least one coexisting weight-related condition. If you also suffer from migraines, this may be a medication to consider, as topiramate is also used to manage migraines.

What the Research Says

In a large industry-funded study called the CONQUER trial, participants taking Qsymia lost at least 5 percent of their body weight on average in eight weeks. Two doses were given: a higher dose of 15 mg to 92 mg and a standard dose of 7.5 mg to 46 mg.

Results showed that participants given the higher amount lost more weight.

A 2012 follow-up trial called the SEQUEL trial suggested Qsymia was a well-tolerated and effective option for weight loss in those with cardiovascular disease.

Cost

Most insurance plans cover the cost of Qsymia. Without coverage, the average monthly price starts around $128, depending on the dose.

Safety and Side Effects

Possible side effects of taking Qsymia include altered taste, insomnia, constipation, dry mouth, prickling sensation, and dizziness, according to research.

It also contains phentermine, a known stimulant and controlled substance. You shouldn’t take Qsymia if you have certain medical conditions, such as uncontrolled high blood pressure, coronary artery disease, hyperthyroidism, glaucoma, and sensitivity to stimulants.

RD Verdict

Compared with phentermine alone, Qsymia appears more effective for weight loss and can be prescribed for longer than 12 weeks. But there’s still potential for dependence.

3. Contrave (Naltrexone and Bupropion)

Contrave is another FDA-approved prescription-only weight loss medication that combines naltrexone and bupropion. Naltrexone is an opioid antagonist for opioid dependence, and bupropion is an antidepressant.

How It Works

Contrave works on the brain to reduce hunger and cravings. It does this by targeting the brain’s appetite regulation center and reward system to reduce the desire for food, according to research.

It’s taken once daily to start and then gradually increases in dose to an eventual schedule of two tablets twice daily.

Who Is Eligible?

You’re eligible with a BMI of 30 or greater or a BMI of 27 or higher with at least one coexisting weight-related condition. Since this medication works as an antidepressant and targets the brain's reward centers, it may be particularly helpful if you’re an emotional eater.

What the Research Says

Those who take Contrave report reduced appetite and cravings. Two major clinical trials were done on Contrave: the Greenway and the Wadden trials. These studies used different doses of Contrave for 56 weeks versus a placebo.

Those who took the highest dose lost the most weight, followed by the lower amount, and then the placebo. In both studies, at least half the Contrave participants lost at least 5 percent of their body weight.

Cost

Some insurance plans cover the cost of Contrave. If not, the price is $99 per month.

Safety and Side Effects

The most common side effects of Contrave are nausea, headaches, dizziness, constipation, and dry mouth, according to research. Bupropion may interact with some medications, so discussing use with your doctor is essential.

More rare but potentially serious side effects include high blood pressure, liver damage, and glaucoma.

Contrave has a black box warning from the FDA alerting users that it may increase the risk of suicidal thoughts or behaviors.

RD Verdict

Contrave has the potential to help you lose weight when combined with diet and exercise. Studies also show weight loss maintenance for at least a year with continued use.

4. Orlistat (Xenical)

Orlistat is another FDA-approved prescription weight loss medication in capsule form. You may be familiar with Orlistat’s over-the-counter version, Alli, available at a lower dose.

How It Works

Orlistat is a lipase inhibitor, which helps block the enzymes that break down fat. This helps reduce fat absorption from your diet, and thus many calories pass through your body, says research.

The dosage for Orlistat is 120 mg three times daily with each meal that contains fat. For Alli, the dose is 60 mg with each meal.

Who Is Eligible?

You qualify if you have a BMI of 30 or greater or a BMI of 27 or greater with at least one coexisting weight condition.

What the Research Says

One 24-week study showed those taking Orlistat lost 5.63 percent of their body weight compared to 2.3 percent in the placebo group. Results suggested Orlistat led to a significant reduction in weight, BMI, and waist circumference.

A study published in 2022 also showed Orlistat’s potential to decrease precursors to cholesterol called oxysterols. This highlights that Orlistat may play a role in overall heart health and weight management.

Cost

Some insurances cover the cost of Orlistat when deemed medically necessary. If not, the typical price is $100 a month.

Safety and Side Effects

The most common side effects from Orlistat are gastrointestinal. Because it prevents fat absorption, it can lead to fecal spotting, diarrhea, and abdominal pain, says research.

While these side effects are mild, 70 to 80 percent of those taking Orlistat experience them at some point, according to research. These same side effects can occur with the OTC version, Alli.

You may lessen your risks of these side effects by following a low-calorie diet with less than 30 percent of calories from fat, research suggests.

RD Verdict

Orlistat can produce weight loss, but digestive side effects are common because of how it works.

5. Plenity

Plenity is an FDA-approved, prescription-only weight loss aid. It’s taken as a capsule but is considered a medical device because of its mechanical action. It’s newer to the market than the other weight loss pills but has garnered much attention.

How It Works

Three Plenity capsules are taken twice daily, 20 minutes before lunch and dinner. It’s made from two natural ingredients: cellulose and citric acid. Cellulose is a structural component of vegetables and is not digested by the body.

When Plenity moves through the body, the cellulose combines with water to form tiny crystals called hydrogels. These structures provide an enhanced feeling of fullness, research suggests.

Who Is Eligible?

Plenity differs from the best weight loss pills on this list, as you’re eligible with a BMI of 25 or greater (versus a BMI of 27).

What the Research Says

According to the research to date, Plenity appears to be a safe and effective weight loss aid in conjunction with a healthy diet and lifestyle. Since it’s a newer product, little research has been conducted yet.

One 24-week randomized study called the GLOW study was done on Plenity in 2020. In this study, participants took three capsules of Plenity before lunch and dinner. Those who took Plenity achieved a 6.4 percent weight loss on average versus 4.4 percent in the placebo group.

There wasn’t a higher incidence of side effects in the Plenity group compared with the placebo group.

Cost

Some insurance plans cover Plenity. If not, it may be covered through an HSA (health savings account) or FSA (flexible spending account) if you have these benefits through your insurance.

The out-of-pocket cost is $98 for a four-week supply. You can also receive a 15 percent discount by purchasing a 12-week supply for $249.

Side Effects and Safety

The most common side effects of Plenity reported by users are fullness, bloating, gas, or abdominal pain, says research. No severe side effects have been reported.

RD Verdict

While the research is still new, Plenity has the potential to be an effective natural weight loss aid with a strong safety profile.

When choosing from this list of best weight loss pills, it’s important to consider your health status and long-term sustainability.

Many of these weight loss pills may need to be taken long-term to sustain weight loss, and more research is needed on this topic.

Because of this, it’s recommended that you use these weight loss pills under the guidance of a medical professional or registered dietitian — especially if you decide to go off them. A health professional can help you stay on track and motivated to reduce the risk of weight regain.

The Takeaway

Several weight loss pills are out there to support your health and wellness goals. When seeking the best weight loss pill for you, it’s important to understand the research and be aware of potential side effects.

A holistic approach to weight loss that includes a healthy diet, exercise, and weight loss pills when needed will yield the biggest, most long-lasting results.

Always consult a healthcare professional for personalized guidance and to determine if a weight loss pill should be added to your health plan.

This content is meant to be informative, but should not be taken as medical advice. It is not intended for use as diagnosis, prevention, or treatment of health problems. Always speak with your doctor before trying new pills, supplements, or regimens.