The Most Popular Weight Loss Medications and Supplements Reviewed

As the rates of overweight and obesity continue to climb worldwide, many people are searching for effective ways to shed excess pounds and improve their health. While some prefer to rely on natural methods, such as dietary changes and exercise, others are turning to weight loss medications and supplements for extra help.

If you're considering using pills or drugs to help with weight loss, it's essential to understand the potential benefits and risks involved. Prescription medications, such as GLP-1 agonists, orlistat, and setmelanotide, are generally considered more effective than many over-the-counter options, which may lack scientific evidence or contain unreliable ingredients.

Key Takeaway

Weight loss medications and supplements may offer a tempting solution for those struggling with excess weight, but it's important to remember that they come with potential risks and side effects. Medications such as GLP-1 receptor agonists have been shown to be effective for weight loss in certain individuals, but they should only be taken under the guidance of a healthcare professional. Similarly, while some supplements such as green tea extract and glucomannan may offer mild benefits, others like bitter orange and forskolin have limited evidence and may pose health risks.

Weight loss medications work by affecting various aspects of your body's metabolism and appetite. For instance, GLP-1 agonists mimic a hormone that regulates blood sugar and reduce food intake by making you feel full faster. Orlistat blocks the absorption of dietary fat, resulting in fewer calories consumed. Setmelanotide targets a specific genetic mutation that can cause severe hunger and obesity.

However, these medications are not magic pills and should not be seen as a quick fix for weight loss. They can have side effects, interact with other medications, and may not work for everyone. Therefore, it's crucial to consult a healthcare professional before starting any weight loss medication or supplement and to follow their guidance closely.

In addition to prescription options, there are many over-the-counter weight loss supplements available, ranging from herbal remedies to synthetic compounds. Some of these products may claim to boost your metabolism, burn fat, or suppress your appetite, but their effectiveness and safety are often uncertain.

To help you navigate the crowded weight loss supplement market, we've reviewed the most popular products based on scientific research. Our list includes natural and synthetic supplements, as well as prescription medications, to provide you with a comprehensive overview of the options available. By knowing the facts and myths behind each supplement, you can make an informed decision about which one, if any, is right for you.

Weight-loss medications should only be used in people who have health problems related to overweight or obesity. They should not be used for cosmetic weight loss. Benefits of weight-loss medications include improvements in blood pressure, blood cholesterol, and blood sugars. Weight-loss medications can be expensive and are not always covered by insurance.

Dr. Susan Z. Yanovski, MD, Chief of Obesity Research at the NIDDK

Prescription Weight Loss Medications

Pentermine / Topiramate

Phentermine/topiramate, marketed under the brand name Qsymia, is a prescription medication that belongs to the class of drugs called sympathomimetic amines. This medication is used to promote weight loss and reduce the risk of obesity-related health problems.

Phentermine/topiramate contains two active ingredients. The first is phentermine, which is a central nervous system stimulant and appetite suppressant. The second is topiramate, an anticonvulsant that can help to reduce appetite and increase feelings of fullness. Together, these ingredients work to promote weight loss by reducing calorie intake and increasing energy expenditure.

Studies have shown that phentermine/topiramate can be effective in promoting weight loss. One review found that it led to an average weight loss of 17 pounds and a significant reduction in belly fat, blood pressure, blood sugar, and cholesterol levels. Another study found that people with obesity who took phentermine/topiramate for a year lost an average of 19.4 pounds.

Like all medications, phentermine/topiramate has some potential side effects. The most common ones include dry mouth, constipation, and a sensation of pins and needles. However, it can also cause increased body temperature, an inability to sweat, and psychiatric or cognitive disturbances.


Orlistat is a medication that has been approved for weight loss by the US Food and Drug Administration (FDA). It's available both by prescription and over the counter, under the brand names Xenical and Alli, respectively.

The mechanism of action of orlistat is quite interesting. It works by blocking the action of certain enzymes that are responsible for breaking down fats in the digestive system. This means that less fat is absorbed by the body, which leads to a reduction in calorie intake.

Research has shown that orlistat can be effective in promoting weight loss. In a study involving 80 people with obesity, those who took orlistat lost an average of 10.3 pounds over a period of six months. This weight loss was accompanied by a reduction in body mass index (BMI), belly fat, and cholesterol levels.

However, like most medications, orlistat does have side effects. Many people who take orlistat report experiencing digestive issues, such as loose stools, oily stools, gas, and frequent bowel movements. This is because the medication interferes with the normal processing of fats in the body. To reduce these side effects, it's recommended that people taking orlistat follow a low-fat diet.

Additionally, orlistat can lead to nutrient deficiencies, especially in fat-soluble vitamins like A, D, E, and K. This is because these vitamins require dietary fat for absorption, which orlistat reduces. Therefore, it's important to talk to your healthcare provider about taking vitamin supplements while on orlistat.

If you're considering taking orlistat for weight loss, it's important to discuss it with your doctor or a qualified healthcare provider. They can help you determine if the medication is right for you and provide guidance on how to use it safely and effectively.

GLP-1 Agonists: Liraglutide and Semglutide

GLP-1 agonists are a class of drugs that have been approved for weight loss. These medications work by slowing down the emptying of the stomach, increasing feelings of fullness, and reducing the secretion of glucagon, a hormone involved in regulating appetite.

Two GLP-1 agonists that have been approved for weight loss are liraglutide, marketed under the brand name Saxenda, and semaglutide, sold as Wegovy. Both are self-administered injections, but liraglutide is taken once a day while semaglutide is injected only once a week.

Other GLP-1 agonists that are used to treat type 2 diabetes, such as semaglutide (Ozempic or Rybelsus), dulaglutide (Trulicity), and exenatide (Byetta), are sometimes prescribed off-label for weight management.

Studies have shown that GLP-1 agonists can be effective for weight management. For instance, one study found that taking 2.4 mg of semaglutide per week combined with lifestyle changes led to a nearly 15% reduction in body weight after 68 weeks. Another study found that people taking liraglutide lost an average of 17.2 pounds over 6 months.

Like all medications, GLP-1 agonists can have side effects. Common ones include nausea, vomiting, diarrhea, dizziness, headaches, and increased heart rate. More serious side effects, such as kidney problems, thyroid C-cell tumors, gallbladder disease, low blood sugar, and suicidal ideation, are rare but have been reported.

It's important to talk to your healthcare provider before taking GLP-1 agonists for weight loss. They can evaluate your health history and determine if the medication is right for you. They can also provide guidance on how to use the medication safely and effectively and monitor you for any potential side effects or complications.

Contrave: Naltrexone / Bupropion

Contrave is a prescription medication that combines two drugs, naltrexone and bupropion, to promote weight loss. Naltrexone is a medication used to treat opioid or alcohol use disorder, while bupropion is an antidepressant that can help to reduce appetite and cravings.

The exact mechanism of action of Contrave is not fully understood, but it's thought to work by affecting certain areas of the brain that control appetite, metabolism, and satiety. By reducing food intake and increasing feelings of fullness, Contrave can help people lose weight.

Studies have shown that Contrave can be effective in promoting weight loss. In one review of four studies, participants who took Contrave lost an average of 11 to 22 pounds over the course of a year, compared to those who took a placebo. Another review found that Contrave could be effective for long-term weight loss maintenance as well.

Like all medications, Contrave can have side effects. Common side effects include nausea, constipation, headache, vomiting, dizziness, and insomnia. It may also increase heart rate and blood pressure.

If you're considering taking Contrave for weight loss, it's important to talk to your doctor or a qualified healthcare provider. They can help you determine if the medication is right for you and provide guidance on how to use it safely and effectively. They can also monitor you for any potential side effects or complications.

Setmelanotide: Imcivree

Setmelanotide, marketed as Imcivree, is a prescription-only injectable medication used for treating obesity caused by certain genetic mutations. It belongs to a class of medications known as melanocortin 4 (MC4) receptor agonists.

People with specific genetic mutations may experience insufficient activation of the MC4 receptor in the brain, which could lead to obesity. Setmelanotide works by increasing the activation of this receptor, which reduces hunger, decreases calorie intake, and increases metabolism, all of which could promote weight loss.

Several studies have found setmelanotide to be effective in promoting weight loss. For instance, one study in 21 people taking setmelanotide found that around 62% of participants achieved at least 10% weight loss after 1 year. Another small study in children, adolescents, and adults found that setmelanotide significantly improved quality of life as early as 5 weeks after starting treatment.

Like all medications, setmelanotide can have side effects. Some of the most common side effects include injection site reactions, hyperpigmentation, nausea, headache, diarrhea, and stomach or back pain. Fatigue, vomiting, and depression have also been reported.

Appetite Suppressants

Appetite suppressants are medications that can help reduce feelings of hunger, making it easier to consume fewer calories and lose weight. Phentermine (Adipex-P or Lomaira), benzphetamine (Regimex or Didrex), diethylpropion (Tepanil or Tenuate), and phendimetrazine (Bontril) are all examples of appetite suppressants that are available only with a prescription.

These medications work by altering the levels of neurotransmitters in the brain that regulate hunger and appetite, ultimately leading to weight loss. However, it’s important to note that these medications are only recommended for short-term use, as they can cause tolerance and decreased effectiveness over time.

Studies have shown that phentermine can result in an average weight loss of 8.3 pounds (3.75 kg) over 12 weeks, while diethylpropion can lead to an average weight loss of 10.8 pounds (4.9 kg) after 3 months and 17 pounds (7.7 kg) after 6 months. However, these medications can cause side effects such as nausea, vomiting, diarrhea, and stomach cramps, and more severe side effects like shortness of breath and chest pain may require immediate medical attention.

Over the Counter Weight Loss Options


Caffeine, the world's most commonly consumed psychoactive substance, is often added to commercial weight loss supplements due to its metabolism-boosting properties. Found in coffee, green tea, and dark chocolate, caffeine increases energy expenditure by increasing fat breakdown and producing body heat through thermogenesis.

Studies have shown that caffeine can cause modest weight loss in humans.

However, high amounts can cause side effects such as anxiety, insomnia, jitteriness, irritability, nausea, and diarrhea. Furthermore, caffeine is addictive and can reduce the quality of sleep. Rather than taking supplements or pills containing caffeine, it is recommended to consume quality coffee and green tea, which contain antioxidants and other health benefits.

Green Coffee Bean Extract

Green coffee bean extract has been touted as a natural weight loss supplement. As the name suggests, it is derived from unroasted coffee beans, which contain caffeine and chlorogenic acid. Caffeine is known to boost metabolism and increase fat burning, while chlorogenic acid slows the breakdown of carbohydrates in the gut.

Several human studies have shown that green coffee bean extract can help with weight loss. A meta-analysis of randomized control trials revealed that it had a significant impact on reducing body mass index. Additionally, green coffee bean extract may have other health benefits, such as reducing blood sugar levels and blood pressure, and being high in antioxidants.

However, it can cause the same side effects as caffeine, such as jitteriness and dehydration. Chlorogenic acid may also cause diarrhea, and some people may be allergic to green coffee beans.

Green Tea Extract

Green tea extract is a popular ingredient in weight loss supplements, and for good reason. The main antioxidant in green tea extract, EGCG, has been shown to aid fat burning and potentially treat obesity. By hindering enzymes such as pancreatic lipase, green tea extract can reduce fat absorption and increase fat burning, especially when combined with exercise.

Several human studies have shown the effectiveness of green tea extract in promoting fat loss, particularly in the belly area.

Although generally well tolerated, green tea extract does contain caffeine and may cause symptoms in caffeine-sensitive individuals. However, green tea extract also contains all the health benefits of drinking green tea, including reduced inflammation, improved brain function, and a lowered risk of several chronic diseases.

It's important to note that while studies have used doses of 500 mg of green tea extract or more, a typical cup of green tea only contains approximately 50-100 mg of green tea extract.


Hydroxycut is a well-known weight loss supplement that has been on the market for over a decade. It contains several ingredients that are purported to aid in weight loss, including caffeine and plant extracts such as green coffee extract. Studies have shown that supplementation with green coffee extract led to a weight loss of about 5.5 pounds compared to a placebo.

However, if you are sensitive to caffeine, you may experience side effects such as anxiety, jitteriness, tremors, headaches, dizziness, and dehydration. It's important to note that Hydroxycut supplements containing ephedra, a stimulant herb, were removed from shelves due to cardiovascular risks in 2004 and hepatotoxicity in 2009. Acute liver injury has also been linked to the use of Hydroxycut supplements, so it's important to proceed with caution when considering this weight loss supplement.

Garcinia Cambogia

Garcinia cambogia extract is a fruit-based supplement that gained popularity after being featured on “The Dr. Oz Show” in 2012. The active ingredient in the extract is hydroxycitric acid, which is thought to reduce cravings and hinder the body’s fat production.

However, the evidence on the effectiveness of this supplement for weight loss is mixed. While some studies suggest it can cause modest weight loss, a meta-analysis found no significant effect on body weight or fat percentage compared to a placebo.

Moreover, recent studies have raised concerns about serious side effects, including acute liver failure and liver impairment. Therefore, it is important to consult with a healthcare professional before taking this supplement.


Orlistat, sold under the brand name Alli over the counter and Xenical by prescription, is a pharmaceutical drug designed to help with weight loss.

How it works is by preventing the breakdown of fat in the gut, meaning that fewer calories are absorbed from fat intake. When combined with lifestyle changes, such as a healthy diet and exercise, studies have shown it to be effective in producing a greater reduction in weight compared to a placebo group.

Additionally, Orlistat may also offer other benefits, such as slightly reducing blood pressure and the risk of developing type 2 diabetes when used alongside lifestyle changes.

However, Orlistat also comes with digestive side effects, such as loose, oily stools, flatulence, and frequent bowel movements that can be difficult to control. It's also possible to develop a deficiency in fat-soluble vitamins when taking this medication.

To minimize side effects, it's recommended to follow a low-fat diet while taking Orlistat. Interestingly, a low-carb diet has been shown to be just as effective for weight loss without medication. However, Orlistat combined with a low-carb diet has been found to be more effective in lowering blood pressure compared to a low-fat diet.

CLA Conjugated Linoleic Acid

If you're looking for a fat loss supplement that is derived from animal-derived foods, CLA might be on your radar. CLA is a type of trans fat found naturally in some fatty foods like cheese and butter.

It works by reducing appetite, boosting metabolism, and stimulating the breakdown of body fat. However, the effectiveness of CLA in helping people lose weight is debatable. While one study found that taking 3,000 mg of CLA per day for three months led to a significant reduction in body fat mass and percentage, body weight and BMI were not significantly affected.

Furthermore, CLA can cause various digestive side effects, and long-term use may have harmful effects, potentially contributing to fatty liver, insulin resistance, and increased inflammation. Therefore, it's essential to talk to your doctor before taking any supplements containing CLA.

Raspberry Ketones

Raspberry ketones are a popular weight loss supplement that are derived from raspberries.

These ketones have been found to increase the breakdown of fat cells and elevate levels of adiponectin, a hormone that is believed to play a role in weight loss. However, while some studies have suggested that raspberry ketones may be effective in promoting weight loss, most of the evidence thus far has been limited to animal studies.

In animal studies, high doses of raspberry ketones have been associated with liver dysfunction and elevated blood sugar levels. Further research is necessary to determine whether raspberry ketones are a safe and effective weight-loss supplement for humans.

Bitter Orange

Bitter orange, a type of orange containing the compound synephrine, is a weight loss supplement often touted for suppressing appetite and increasing fat burning.

However, it's important to note that the FDA has banned the use of ephedrine, a similar compound to synephrine, due to its harmful side effects. While synephrine is less potent than ephedrine, it may still pose a risk to heart health and lead to dependence.

Additionally, studies on the effectiveness of synephrine for weight loss have yielded mixed results. While some older research has suggested it could be effective, a recent review concluded that it may not be effective and could increase blood pressure and heart rate with prolonged use.

More research is needed on this supplement before its safety and efficacy can be determined.


Glucomannan is a type of fiber that has been gaining popularity as a weight loss supplement. This fiber is extracted from the roots of the elephant yam, and is also known as konjac. It works by absorbing water and swelling up, creating a feeling of fullness in the gut, which can help reduce calorie intake.

Research has shown that taking glucomannan consistently for 60 days can lead to lower body weight in people with overweight. But it’s important to note that results may vary and it’s not a magic solution for weight loss.

Aside from its potential as a weight loss aid, glucomannan also offers other health benefits. It’s a fiber that can feed the friendly bacteria in the intestine, improving gut health. It can also lower fasting blood sugar and blood cholesterol, and is effective against constipation.

However, taking glucomannan supplements can come with some side effects, including bloating, flatulence, and soft stools. It can also interfere with some oral medications if taken at the same time. To avoid these side effects, taking glucomannan about half an hour before meals with a glass of water is important.


Forskolin is a weight loss supplement derived from a plant in the mint family. Although it is believed to work by stimulating fat burning, the research is limited and inconclusive.

One study suggested it could reduce body fat and increase muscle mass, but another found no effects. More research is needed to determine its potential effectiveness.

There is also little information on its safety and possible side effects, so caution is advised when considering using forskolin for weight loss.


Meratrim is a relatively new weight loss supplement on the market that uses a combination of two plant extracts. It claims to reduce the amount of fat that fat cells pick up from the bloodstream, make it harder for fat cells to multiply, and help them burn stored fat.

Unfortunately, there are very few studies on the effectiveness of Meratrim, and more research is needed to support its claims. However, one 2012 study showed promising results, with participants losing 11 pounds and 4 inches off their waistlines after 16 weeks. Another study suggested that Meratrim may have lasting effects on appetite suppression.

The good news is that no side effects have been reported.

Final Thoughts

If you've been struggling with weight loss despite trying different methods, it may be time to seek help from a healthcare professional such as a doctor or a registered dietitian. These experts can assess your situation and determine if weight loss medication may be a viable option for you.

It's important to remember that weight loss drugs and supplements can have serious side effects and may not be safe for everyone. This is why it's crucial to consult with a professional before taking any weight loss medication or supplement.

Wynne Lee, MD

Dr. Wynne Lee is a physician at Massachusetts General Hospital (MGH), where she provides primary care.

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