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Weight Loss Medications: Do They Work?

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Weight Loss Medications: Do They Work?

Prescription weight loss medications, including GLP-1 agonists, orlistat, and setmelanotide, 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:

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 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 to support weight management.

Most work by reducing your food intake, decreasing fat absorption, or increasing fat-burning, resulting in significant weight loss over time.

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

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

Not only will adopting dietary and lifestyle changes help increase the effectiveness of weight loss drugs, they can also help minimize weight regain, which often occurs after you stop taking these medications.

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

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, 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.

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 constipation, 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: This medication is 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.

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: chronic malabsorption, cholestasis (a type of liver disease), pregnancy, renal impairment, and current use of certain prescription medications.

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

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 (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, pregnancy, recent use of monoamine oxidase inhibitors, and current use of certain prescription medications.

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. Over 1 year, participants lost 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, and insomnia. It might also increase heart rate and blood pressure.

Contraindications: This medication is not recommended for people with a history of seizures, end-stage renal disease, pregnancy, and current use of 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 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.

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.

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. However, phentermine (Adipex-P or Lomaira) is the most commonly prescribed.

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 overweight and at least one weight-related condition, such as:

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 people who are pregnant, those with certain health conditions, or individuals taking specific medications.

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.

Weight loss medications are not recommended during pregnancy and may not be safe for people who are pregnant or who may become pregnant, or anyone who’s breastfeeding. Contact a trusted healthcare professional, like your OB-GYN, before taking any weight loss medications or supplements.

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.

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

Studies also suggest that people with higher body weights are disproportionately more likely to experience disordered eating and eating disorder symptoms.

If you’re 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.

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.

Saxenda (liraglutide), Wegovy (semaglutide), and tirzepatide (Zepbound) are three GLP-1 medications recently approved for weight loss. Other GLP-1 medications, such as Ozempic (semaglutide), are also sometimes prescribed off-label for weight management.

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.

Finally, it’s important to remember that these products should not be considered a “quick fix” for weight loss. Obesity is a chronic condition, and medications are just one part of a treatment plan to help achieve and maintain 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.

Last medically reviewed on November 17, 2023

Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available.

Rachael Ajmera, MS, RD, Kris Gunnars

Jerlyn Jones, MS MPA RDN LD CLT

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