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Prescription weight loss medications, including GLP-1 agonists, orlistat, and setmelanotide, are more likely to be effective for weight loss than many over-the-counter options.

There are many possible weight loss solutions out there.

Some options are more popular than others, including certain pills, drugs, and natural supplements. These claim to help you lose weight, or at least to make it easier to lose weight when you combine them with other methods.

They tend to work via one or more of these mechanisms:

  • reducing appetite, making you feel fuller so you eat fewer calories
  • reducing absorption of nutrients such as fat, making you take in fewer calories
  • increasing fat burning, making you burn more calories

Various options are available, including over-the-counter (OTC) supplements and prescription medications.

However, you should always discuss any diet or supplement changes with a healthcare professional, such as a doctor or registered dietitian, and use medications or OTC pills only as directed.

To separate the myths from facts, here are the 18 most popular weight loss medications and supplements, reviewed by science.

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Several drugs have been approved by the Food and Drug Administration (FDA) for weight loss for overweight and obesity. These medications require a prescription from a doctor and should only be taken under medical supervision.

These include (1):

  • orlistat (Xenical)
  • phentermine/topiramate (Qsymia)
  • naltrexone/bupropion (Contrave)
  • glucagon-like peptide 1 (GLP-1) agonists, including liraglutide (Saxenda) and semaglutide (Wegovy)
  • setmelanotide (Imcivree)
  • appetite suppressants, including phentermine (Adipex-P or Lomaira), benzphetamine (Regimex or Didrex), diethylpropion (Tepanil or Tenuate), and phendimetrazine (Bontril)

These medications should be combined with a balanced weight loss diet, as they are not likely a helpful long-term solution to obesity and may lead to weight regain over time. They also have many possible side effects, some of which can be serious.

Quick look at prescription weight loss medications

1. Orlistat (Xenical)

Orlistat is an oral medication that is available via prescription as Xenical. It can also be purchased over the counter as the brand Alli.

After a medical consultation, a doctor can prescribe orlistat. Certain telehealth services can also provide a prescription for this medication.

How it works: Orlistat works by blocking the activity of certain enzymes used to break down fats in the digestive tract, which helps to reduce the amount of calories that you absorb (2).

Effectiveness: According to a 2011 study of 80 people with obesity, those who took orlistat lost an average of 10.3 pounds (lb), or 4.65 kilograms (kg), after 6 months. They also experienced significant reductions in body mass index (BMI), belly fat, and total and LDL (bad) cholesterol levels (3).

Side effects: Orlistat often causes digestive issues like loose or oily stools, gas, and frequent bowel movements. It could also contribute to nutrient deficiencies, including in fat-soluble vitamins A, D, E, or K (4).

Following a low fat diet is typically recommended while taking this medication to help minimize adverse side effects.

2. Phentermine/topiramate (Qsymia)

Phentermine/topiramate is an oral medication that belongs to a class of drugs known as sympathomimetic amines. It requires a prescription from a doctor and is sold under the brand, Qsymia.

How it works: This medication includes phentermine, a central nervous system stimulant and appetite suppressant with similar mechanisms to amphetamine. It also includes topiramate, an anticonvulsant that helps reduce appetite and enhance satiety to promote weight loss (5).

Effectiveness: One review concluded that phentermine/topiramate resulted in an average weight loss of 17 lb (7.7 kg) and significantly reduced belly fat, blood pressure, blood sugar, and cholesterol levels (6).

Another review comparing the effectiveness of several weight loss medications found that people with overweight or obesity who took phentermine/topiramate lost an average of 19.4 lb (8.8 kg) after 1 year (7).

Side effects: The most common side effects associated with phentermine/topiramate include dry mouth, constipation, and paresthesia, or a sensation of pins and needles (5).

It could also cause increased body temperature, an inability to sweat, and psychiatric or cognitive disturbances (5).

3. Naltrexone/bupropion (Contrave)

This medication, sold under the name Contrave, is an oral medication that combines bupropion, an antidepressant, and naltrexone, which is used to manage opioid or alcohol use disorder (8).

A doctor can determine whether Contrave may be a good option for you and may provide a prescription. Some online services may also prescribe Contrave following a virtual consultation with a healthcare professional.

How it works: Though the exact mechanism of naltrexone/bupropion is not fully understood, it’s believed to promote weight loss by acting on certain parts of the brain to reduce food intake, boost metabolism, and increase feelings of fullness (8).

Effectiveness: One review of four studies showed that naltrexone/bupropion was associated with significant weight loss compared to a placebo. Over 1 year, participants lost an average of 11–22 lb (5–9 kg) (9).

Another review had similar findings, reporting that naltrexone/bupropion could be effective for long-term weight loss maintenance as well (10).

Side effects: Naltrexone/bupropion may cause nausea, constipation, headache, vomiting, dizziness, and insomnia. It might also increase heart rate and blood pressure (8).

4. GLP-1 agonists

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Two GLP-1 agonists have been approved for weight loss, including liraglutide (Saxenda) and semaglutide (Wegovy). Both are available as a self-administered injection, but liraglutide is administered once daily while semaglutide is only injected once per week (11, 12).

Though not approved specifically for weight loss, some other GLP-1 agonists intended to treat type 2 diabetes are also sometimes prescribed off-label for weight management, including (13):

  • semaglutide (Ozempic or Rybelsus)
  • dulaglutide (Trulicity)
  • liraglutide (Victoza)
  • exenatide (Byetta)
  • exenatide extended-release (Bydureon BCise)
  • tirzepatide (Mounjaro)

GLP-1 agonists are only available through a prescription from a doctor. Several telehealth services and weight loss programs can also provide a prescription if you meet the eligibility criteria, including Ro Body Program and Calibrate.

How it works: GLP-1 agonists work by slowing the emptying of the stomach, increasing feelings of fullness, and reducing the secretion of glucagon, a hormone involved in regulating appetite (14).

Effectiveness: Several studies have found that GLP-1 agonists could be beneficial for weight management.

For instance, one study in 1,961 adults found that taking 2.4 milligrams (mg) of semaglutide per week combined with lifestyle changes resulted in a nearly 15% reduction in body weight after 68 weeks (15).

Another small study found that people taking liraglutide lost an average of 17.2 lb (7.8 kg) over 6 months (16).

Side effects: Common side effects include nausea, vomiting, diarrhea, dizziness, headaches, increased heart rate, infections, and indigestion (14).

Though uncommon, severe side effects have also been reported, which may require medical attention, including kidney problems, thyroid C-cell tumors, gallbladder disease, low blood sugar, and suicidal ideation (11, 12).

More research is also needed on the long-term effects of these medications, as there is concern about potential weight regain over time.

5. Setmelanotide (Imcivree)

Setmelanotide, sold as Imcivree, is in a class of medications known as melanocortin 4 (MC4) receptor agonists. It’s an injectable medication approved for treating obesity caused by certain genetic mutations and is available only via prescription (17).

How it works: People with specific genetic mutations may experience insufficient activation of the MC4 receptor in the brain, which could contribute to obesity.

Setmelanotide works by increasing the activation of this receptor, leading to reduced hunger, decreased calorie intake, and increased metabolism, all of which could promote weight loss (18).

Effectiveness: One study in 21 people taking setmelanotide found that around 62% of participants achieved at least 10% weight loss after 1 year. Participants also experienced a significant reduction in hunger with no serious treatment-related adverse events reported (19).

Another small study in children, adolescents, and adults found that setmelanotide significantly improved quality of life as early as 5 weeks after starting treatment, which could be related to reduced hunger and body weight (20).

Side effects: Some of the most common side effects of setmelanotide include injection site reactions, hyperpigmentation, nausea, headache, diarrhea, and stomach or back pain. Fatigue, vomiting, and depression have also been reported (18).

6. Appetite suppressants

There are several anorectics, or appetite suppressants, available, including phentermine (Adipex-P or Lomaira), benzphetamine (Regimex or Didrex), diethylpropion (Tepanil or Tenuate), and phendimetrazine (Bontril).

These are all taken orally and require a prescription from a doctor or other healthcare professional.

How it works: These medications reduce appetite by altering levels of certain neurotransmitters in the brain, which can lead to weight loss (21).

Effectiveness: One study in 3,411 people compared the effectiveness of several medications for obesity and found that people taking phentermine lost the highest percentage of body weight over 12 weeks. Those taking phentermine lost an average of 8.3 lb (3.75 kg) throughout the study (22).

Another 2015 study in 156 people with obesity showed that people taking diethylpropion lost an average of 10.8 lb (4.9 kg) after 3 months and 17 lb (7.7 kg) after 6 months (23).

However, keep in mind that these medications are only recommended for short-term use, as you can build up a tolerance after several weeks, resulting in decreased effectiveness (24, 25, 26, 27).

Side effects: Potential side effects of these medications may include nausea, vomiting, diarrhea, and stomach cramps (24, 25, 26, 27).

Other severe side effects have also been reported and require immediate medical attention, including shortness of breath, chest pain, and swelling of the lower extremities (24, 25, 26, 27).

Quick look at OTC weight loss pills

1. Garcinia cambogia extract

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Garcinia cambogia became popular worldwide after being featured on “The Dr. Oz Show” in 2012.

It’s a small, green fruit shaped like a pumpkin. The fruit’s skin contains hydroxycitric acid, the active ingredient in garcinia cambogia extract, which is marketed as a diet pill.

How it works: Animal studies show that it can hinder a fat-producing enzyme in the body and increase serotonin levels, potentially helping to reduce cravings (28, 29).

Effectiveness: According to one meta-analysis of 54 studies, researchers found that garcinia cambogia had no significant effect on body weight or body fat percentage compared to a placebo (30).

On the other hand, a 2020 review that looked at eight trials on garcinia cambogia found that, on average, it caused weight loss of about 3 lb (1.34 kg) (31).

Side effects: While it’s widely agreed that garcinia cambogia is safe to take in recommended amounts, studies within the last several years have pointed to some serious side effects.

A 2018 study documented four cases of women who experienced acute liver failure after taking weight loss supplements containing garcinia cambogia (32).

Additionally, hepatotoxicity, or liver impairment, and some episodes of mania have also been reported in conjunction with taking garcinia cambogia (33, 34).

2. Hydroxycut

Hydroxycut has been around for more than a decade and is one of the most popular weight loss supplements in the world. The brand makes several products, but Hydroxycut is the most common.

How it works: It contains several ingredients claiming to help with weight loss, including caffeine and a few plant extracts such as green coffee extract.

Effectiveness: A 2011 meta-analysis of five clinical trials found that supplementation with C. canephora robusta, or green coffee extract, one of the key ingredients in Hydroxycut, led to about a 5.5-lb (2.47-kg) weight loss compared to the placebo (35).

Side effects: If you are sensitive to caffeine, you may experience anxiety, jitteriness, tremors, headaches, dizziness, and dehydration (36).

Hydroxycut products containing ephedra, a stimulant herb, were removed from shelves due to cardiovascular risks in 2004 and hepatotoxicity in 2009 (37).

Acute liver injury has also been linked to using Hydroxycut supplements (38).

3. Green coffee bean extract

Green coffee beans are coffee beans that haven’t been roasted. They contain two substances believed to help with weight loss, including caffeine and chlorogenic acid.

How it works: Caffeine can increase fat burning, and chlorogenic acid can slow the breakdown of carbohydrates in the gut.

Effectiveness: Several human studies have shown that green coffee bean extract could help people lose weight (39, 40).

A meta-analysis of all the current randomized control trials on green coffee bean extract’s effect on obesity found that the supplement has a significant impact on minimizing body mass index (41).

Other benefits: Green coffee bean extract may help lower blood sugar levels and reduce blood pressure. It is also high in antioxidants (42, 43, 44).

Side effects: It can cause the same side effects as caffeine. The chlorogenic acid it contains may also cause diarrhea, and some people may be allergic to green coffee beans (45).

4. Caffeine

Caffeine is the most commonly consumed psychoactive substance in the world. It is found naturally in coffee, green tea, and dark chocolate and is added to many processed foods and beverages (46).

Because caffeine is considered a metabolism booster, companies commonly add it to commercial weight loss supplements.

How it works: One study discussed the effect of caffeine on regulating body weight by increasing energy expenditure — essentially meaning you burn more calories via increased fat breakdown and through a process of body heat production called thermogenesis (47).

Effectiveness: Some studies show that caffeine can cause modest weight loss in humans (48).

Side effects: In some people, high amounts of caffeine can cause anxiety, insomnia, jitteriness, irritability, nausea, diarrhea, and other symptoms. Caffeine is also addictive and can reduce the quality of your sleep (49).

There is no need to take a supplement or a pill containing caffeine. The best sources are quality coffee and green tea, which have antioxidants and other health benefits (50).

5. Orlistat (Alli)

Orlistat is a pharmaceutical drug sold over the counter under the brand name Alli and via prescription as Xenical.

How it works: This weight loss pill works by inhibiting the breakdown of fat in your gut, meaning that you take in fewer calories from fat.

Effectiveness: A 2021 meta-analysis of studies found that people taking orlistat for 12 months in combination with lifestyle changes saw a 2.9% greater weight reduction than the placebo group (51).

Other benefits: Orlistat has been shown to reduce blood pressure slightly and may reduce the risk of developing type 2 diabetes when used alongside lifestyle changes (52, 53).

Side effects: This drug has many digestive side effects, including loose, oily stools, flatulence, and frequent bowel movements that are hard to control. It may also contribute to a deficiency in fat-soluble vitamins such as vitamins A, D, E, and K (4).

Following a low fat diet while taking orlistat is often recommended to minimize side effects. Interestingly, a low carb diet (without medication) has been considered as effective as orlistat and a low fat diet combined.

Both diets were as effective for weight loss but showed no significant differences in blood sugar and blood lipid levels. However, orlistat combined with a low carb diet was more effective at lowering blood pressure (54).

6. Raspberry ketones

Raspberry ketone is a substance found in raspberries and is responsible for their distinct smell.

A synthetic version of raspberry ketones is sold as a weight loss supplement.

How it works: In isolated fat cells from mice, raspberry ketones increase the breakdown of fat and increase levels of a hormone called adiponectin, which is believed to be related to weight loss (55).

Effectiveness: Though there are very few studies on raspberry ketones in humans, one 2013 study looked at raspberry ketones with some other ingredients and found a potential 2% increase in weight loss over 8 weeks when compared with a placebo (56).

Another mouse study using massive doses showed some delay in weight gain. However, high doses of raspberry ketones were also associated with higher blood sugar levels and higher levels of ALT, a liver enzyme, indicating liver dysfunction (57).

It’s unknown whether these effects would translate to humans. More research is necessary to determine any benefits and risks.

Side effects: According to some anecdotal reports, raspberry ketones can cause your burps to smell like raspberries.

In animal studies, high doses were also associated with increased blood sugar levels and liver dysfunction, though more research in humans is needed (57).

7. Glucomannan

Glucomannan is a type of fiber found in the roots of the elephant yam, which is also called konjac.

How it works: Glucomannan absorbs water and becomes gel-like. It “sits” in your gut and promotes a feeling of fullness, helping you eat fewer calories (58).

Effectiveness: One 2015 clinical trial showed that taking glucomannan for 60 days could lower body weight among participants with overweight, but only if they were consistently taking the supplement (59).

Other benefits: Glucomannan is a fiber that can feed the friendly bacteria in the intestine. It can also lower fasting blood sugar and blood cholesterol and works effectively against constipation (60, 61, 62, 63).

Side effects: Glucomannan can cause bloating, flatulence, and soft stools and can interfere with some oral medications if taken at the same time.

It is important to take glucomannan about half an hour before meals, with a glass of water.

8. Meratrim

Meratrim is a relative newcomer on the diet pill market, made from a combination of two plant extracts — Sphaeranthus indicus and Garcinia mangostana — that may change the metabolism of fat cells.

How it works: It claims to make it harder for fat cells to multiply, decrease the amount of fat they pick up from the bloodstream, and help them burn stored fat.

Effectiveness: Very few studies about Meratrim exist. One 2012 study involved 60 people with overweight placed on a strict 2,000-calorie diet and increased physical activity, with either Meratrim or a placebo. After 16 weeks, the Meratrim group had lost 11 lb (5 kg) and 4 inches (10 centimeters) off their waistlines (64).

Another study suggested that Meratrim had long lasting effects on appetite suppression (65).

Side effects: No side effects have been reported.

9. Green tea extract

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Green tea extract is a popular ingredient in many weight loss supplements. This is because numerous studies have shown that the main antioxidant it contains, EGCG, may aid fat burning.

How it works: Green tea extract is believed to hinder enzymes such as pancreatic lipase, which, when combined with reduced fat absorption, can be an effective way to treat obesity (66).

Effectiveness: Many human studies have shown that green tea extract, when paired with exercise, can increase fat burning and cause fat loss, especially in the belly area (67, 68, 69).

Side effects: Green tea extract is generally well tolerated. It does contain some caffeine and may cause symptoms in people who are sensitive to caffeine.

Additionally, all the health benefits of drinking green tea may also apply to green tea extract. Though, keep in mind that while studies showing benefits of green tea extract use doses of 500 mg per day or more, 1 cup (236 mL) of green tea only contains approximately 50–100 mg of green tea extract.

10. Conjugated linoleic acid (CLA)

CLA has been a popular fat loss supplement for years.

It is known as one of the “healthier” trans fats and is found naturally in some fatty animal-derived foods like cheese and butter.

How it works: CLA may reduce appetite, boost metabolism, and stimulate the breakdown of body fat (70, 71).

Effectiveness: In one study, taking 3,000 mg of CLA per day for 3 months resulted in a significant reduction in body fat mass and body fat percentage, compared to a placebo. However, body weight and BMI were not significantly reduced (72).

Similarly, an older review from 2012 found CLA was linked with an average weight loss of 1.5 lb (0.7 kg), which the authors note may not be clinically meaningful for people trying to lose weight (73).

Side effects: CLA can cause various digestive side effects and may have harmful effects over the long term, potentially contributing to fatty liver, insulin resistance, and increased inflammation.

11. Forskolin

Forskolin is an extract from a plant in the mint family that is thought to be effective for weight loss.

How it works: It may raise levels of a compound inside cells called cAMP, which can stimulate fat burning (74).

Effectiveness: One 2012 study of 30 men with excess weight or obesity showed that forskolin reduced body fat and increased muscle mass while not affecting body weight. Another older study involving 23 women with excess weight found no effects (75, 76).

More recent, high quality research on the potential effectiveness of forskolin is needed.

Side effects: There is minimal data on the safety of this supplement or the risk of side effects.

12. Bitter orange/synephrine

A type of orange called bitter orange contains the compound synephrine.

Synephrine is related to ephedrine, which used to be a popular ingredient in various weight loss pill formulations (77).

However, the FDA has since banned ephedrine as a weight loss ingredient because of serious side effects (78).

How it works: Synephrine has similar mechanisms to ephedrine but is less potent. It could help reduce appetite and increase fat burning (79, 80).

Effectiveness: Very few studies have been done on synephrine, but one older review reported that ephedrine can cause significant short-term weight loss (81).

On the other hand, a more recent 2022 review of 18 studies concluded that synephrine was not effective for weight loss and may increase blood pressure and heart rate with prolonged use (82).

Side effects: Like ephedrine, synephrine may have serious side effects related to the heart. It may also have a high risk of dependence.

If you’ve tried everything to lose weight and the scale still won’t budge, it’s worth talking with a healthcare professional, like a doctor or registered dietitian, about whether a weight loss medication might be right for you.

Because these pills can have serious side effects and are not safe for everyone, it’s important not to take any weight loss drugs or supplements without consulting a professional first.

Some digital weight loss platforms, including Ro and Calibrate, include GLP-1 medications in their treatment plans for people who meet certain eligibility criteria.

You can read our comprehensive reviews of Calibrate and Ro Health to learn more.

Heads up

Weight loss drugs may not be recommended for people with eating disorders (EDs), even if they are at higher body weights, as there is a risk of misuse of prescription or OTC diet drugs (83).

Studies also suggest that people at higher body weights are disproportionately likely to experience disordered eating and eating disorder symptoms (84, 85, 86).

If you are preoccupied with food or weight, feel guilt surrounding your food choices, or routinely engage in restrictive diets, consider reaching out for support. These behaviors may indicate a disordered relationship with food or an ED.

Disordered eating and EDs can affect anyone, regardless of gender identity, race, age, body size, socioeconomic status, or other identities.

They can be caused by any combination of biological, social, cultural, and environmental factors — not just by exposure to diet culture.

Feel empowered to talk with a qualified healthcare professional, such as a registered dietitian, if you’re managing any of these behaviors.

You can also chat, call, or text anonymously with trained volunteers at the National Eating Disorders Association helpline for free or explore the organization’s free and low cost resources.

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How effective are weight loss drugs?

Weight loss medications and supplements can vary in effectiveness.

Some prescription drugs have been shown to cause significant weight loss. However, research is limited on the effectiveness of many OTC supplements, and some studies have even found that certain products — such as synephrine and forskolin — are unlikely to have a significant impact on body weight (75, 76, 82).

Which weight loss medications are best for weight loss?

The best weight loss drug for you depends on your weight loss goals, health status, and personal preferences. Though prescription medications like GLP-1 agonists are supported by stronger research and are more likely to be effective, they may also be associated with adverse side effects and risks.

Keep in mind that regardless of which supplement or medication you choose, it’s important to follow a well-rounded diet and healthy lifestyle. In addition to maximizing your potential results, it can increase the likelihood of maintaining weight loss long-term.

What is the most effective weight loss pill available?

Phentermine is one of the most effective weight loss medications. However, it is only indicated for short-term use. The GLP-1 agonists liraglutide (Saxenda) and semaglutide (Wegovy) are also approved for weight loss and have been shown to be particularly effective. They are considered safe for long-term use (15, 16, 22).

But keep in mind that individual results can vary based on many factors, including your diet, health status, and activity level.

Does insurance cover prescription weight loss medications?

If considered medically necessary, insurance companies may cover certain prescription weight loss medications. Some manufacturers also offer savings cards, which can help lower the cost of your co-pay.

Many weight loss medications and supplements are available, including prescription and OTC options. Overall, prescription medications have stronger evidence to support their effectiveness for meaningful weight loss.

A doctor or other trusted healthcare professional can help you determine which is right for you and how to incorporate it into a healthy weight management plan.

However, it’s important to remember that these medications and supplements should not be considered a “quick fix” for weight loss.

Instead, they should be used only as directed and paired with a balanced diet, healthy lifestyle, and regular physical activity for best results.