Weight Loss Medications: Do They Work?

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Prescription weight loss medications, including GLP-1 agonists, orlistat, and Contrave, may be effective for some people. But other lifestyle changes are still necessary for long-term success.

If it’s challenging to lose weight despite making changes to your diet and increasing your physical activity, you may be wondering whether a prescription weight loss medication is right for you.

These medications tend to work via one or more of these mechanisms:

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

When paired with other lifestyle changes and taken under the supervision of a healthcare professional, these drugs may offer an effective way to lower your weight.

We reviewed all of the weight loss medications that are currently available, including how they work, who they might be appropriate for, research on their effectiveness, and potential safety concerns.

The Food and Drug Administration (FDA) has approved several drugs for losing weight with overweight and obesity. These medications require a prescription from a doctor and should only be taken under medical supervision.

These currently include:

  • GLP-1 agonists, including liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound)
  • orlistat (Xenical and Alli)
  • phentermine/topiramate (Qsymia)
  • naltrexone/bupropion (Contrave)
  • setmelanotide (Imcivree)
  • appetite suppressants, including phentermine (Adipex-P or Lomaira)

These medications should be combined with a balanced weight loss diet, as alone, they’re not likely a helpful long-term solution for obesity and may lead to weight regain over time.

They also have many possible side effects, some of which can be serious.

Weight loss medications can be an effective tool and may support weight management by reducing your food intake, decreasing fat absorption, or increasing your metabolism.

In most cases, these prescription medications can typically result in a loss of 5% to 10% of body weight. However, this can vary depending on several factors, including the specific medication you take.

Keep in mind these medications should be used alongside dietary changes and lifestyle strategies, such as regular physical activity.

Not only can this help increase the effectiveness of weight loss drugs, but it may also help minimize weight regain once you stop taking these medications.

Three GLP-1 agonists have been approved for weight loss, including liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound).

Semaglutide (Wegovy) was also recently approved to reduce the risk of heart attack, stroke, and cardiovascular death in adults with heart disease and overweight or obesity.

All three medications are available as a self-administered injection, but liraglutide is administered once daily, while semaglutide and tirzepatide are only injected once per week.

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

  • 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 or other qualified healthcare professional. Several telehealth services and weight loss programs may also provide prescriptions if you meet the eligibility criteria.

How GLP-1 medications work

GLP-1 agonists work by binding to GLP-1 receptors to mimic the effects of GLP-1, a hormone that helps slow stomach emptying, increase feelings of fullness, and reduce the secretion of glucagon, which is involved in regulating appetite.

Tirzepatide works similarly to other GLP-1 medications but binds to both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors.

Like GLP-1, GIP is another hormone that helps manage blood sugar levels and increases feelings of fullness, thereby promoting weight loss.

Learn more about GLP-1 and GLP-1/GIP agonists in our comprehensive guide.

Effectiveness

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

For instance, one study with 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.

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

More recently, a 2023 phase 3 clinical trial in 2,539 adults found that people taking tirzepatide lost 20% or more of their weight over the course of 72 weeks.

Side effects

Common side effects include nausea, vomiting, diarrhea, dizziness, headaches, increased heart rate, infections, and indigestion.

Though uncommon, severe side effects have also been reported, which may require medical attention. These include kidney problems, thyroid C-cell tumors, gallbladder disease, low blood sugar, and suicidal ideation. It’s important to be in regular contact with your healthcare professional to monitor for these side effects.

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

Contraindications

These medications are not recommended for people with multiple endocrine neoplasia (MEN) syndrome type 2, history of thyroid cancer or pancreatitis, pregnancy, and current use of certain prescription medications.

Additionally, people with severe gastrointestinal conditions, such as gastroparesis and inflammatory bowel disease should avoid taking GLP-1 agonists.

Jargon-buster: “Contraindications” are any reason that someone shouldn’t take a specific medication.

Orlistat is an oral medication that’s 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 may 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 you absorb.

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.

Side effects: Orlistat often causes digestive issues like loose or oily stools, gas, and frequent bowel movements, making the medication difficult for some people to tolerate. It could also contribute to nutrient deficiencies, including in fat-soluble vitamins A, D, E, or K.

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

Contraindications: This medication is not recommended for people with malabsorption, cholestasis (a type of liver disease), renal impairment, and those who are pregnant. Some prescription medications can lead to drug interactions when taking orlistat.

Phentermine/topiramate is an oral medication that 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 (feeling full) to promote weight loss.

Effectiveness: One research 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.

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.

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

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

Contraindications: This medication is not recommended for people with glaucoma (eye conditions that can lead to blindness), a history of hyperthyroidism, recent use of monoamine oxidase inhibitors, current use of certain prescription medications, and those who are pregnant.

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.

A doctor can determine whether Contrave may be a good option for you and then 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 isn’t 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.

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

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

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

Contraindications: This medication is not recommended for people with end stage renal disease, a history of seizures, those who are pregnant, and those who currently take monoamine oxidase inhibitors, opioids, or certain other prescription medications.

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.

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

Setmelanotide works by increasing the activation of these receptors, leading to reduced hunger, decreased calorie intake, and increased metabolism, all of which could promote weight loss.

Effectiveness: Two trials involving 21 people taking setmelanotide found that around 62% of them 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.

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.

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.

Contraindications: This medication is not recommended for people with renal impairment and those who are pregnant or breastfeeding.

There are several anorectics, or appetite suppressants, available, including phentermine (Adipex-P or Lomaira).

Phentermine is taken orally and requires 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.

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.

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.

Side effects: Potential side effects may include nausea, vomiting, diarrhea, and stomach cramps.

Other severe side effects have been reported and require immediate medical attention, including shortness of breath, chest pain, and swelling of the lower extremities.

Contraindications: This medication is not recommended for people with a history of heart disease, hypertension, hyperthyroidism, glaucoma, diabetes, pregnancy, and certain prescription medications.

Most weight loss medications are approved for adults with obesity or with overweight and at least one weight-related condition, such as:

  • type 2 diabetes
  • high blood pressure
  • high cholesterol

Similarly, setmelanotide (Imcivree), is intended to treat obesity caused by certain genetic disorders.

These medications are designed for people who haven’t been able to achieve weight loss through other methods, including diet or lifestyle changes.

Though they shouldn’t be considered a quick fix, these medications can be a useful tool to support weight management when combined with regular physical activity and a nutritious diet.

Keep in mind that weight loss medications are not suitable for everyone, including but not limited to:

  • people who are pregnant or breastfeeding
  • people with certain health conditions
  • people taking specific medications
  • people with eating disorders or disordered eating symptoms

A healthcare professional can provide guidance on whether you might be a candidate for a prescription, depending on your personal goals, medical history, and health status.

If you’ve tried everything to lose weight and the scale 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.

Additionally, with the exception of Alli, which is available over the counter, FDA-approved weight loss drugs require a prescription from a licensed healthcare professional, such as a primary care doctor, nurse practitioner, or physician’s assistant.

If you can’t make an in-person appointment with a healthcare professional, some online weight loss platforms include GLP-1 medications in their treatment plans for people who meet certain eligibility criteria.

Due to drug shortages and demand for weight loss medications, it’s important to get medications from reputable sources prescribed by licensed healthcare professionals to ensure your medication is safe and not counterfeit.

GLP-1 agonists are currently the most effective anti-obesity medications and are considered safe for long-term use.

Currently, only liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound) are approved for weight loss, though some other GLP-1 drugs may be prescribed off-label.

Keep in mind that because of the popularity of Wegovy, there’s currently a nationwide shortage, making the drug difficult to obtain.

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

Additionally, 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 in the long term.

If considered medically necessary, insurance companies may cover certain prescription weight loss medications. Some manufacturers also offer savings cards, which can help lower your copay.

Ozempic and Wegovy are two different brands of the same drug, semaglutide. However, there are differences in the recommended dosage and how each is administered.

Additionally, Wegovy is FDA approved for weight management. While Ozempic is sometimes prescribed off-label to support weight loss, it’s currently only approved to help lower blood sugar levels in people with type 2 diabetes.

Prescription medications have strong evidence to support their effectiveness for meaningful weight loss. However, it’s important to consider eligibility criteria, potential side effects, and whether they’re indicated for long-term use.

Additionally, though they can promote weight loss and may even offer other health benefits, note that these medications are not suitable for everyone and can lead to weight regain once you stop taking them.

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, alongside a balanced diet, healthy lifestyle, and regular physical activity.

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