The pharmacological treatment for obesity is gaining in popularity. There were only a few FDA-approved weight loss drugs before 2012. At that time, the most popular medications were phentermine (marketed under the names Lomaira, Adipex-P and Alli) and orlistat (marketed under Xenical, Alli and Xenical).
Media attention has been sparked by the advent of Glucagon like peptide-1 (GLP-1) receptor agonists, with brands such as Wegovy and Ozempic. According to a 2022 study in Frontiers in Cardiovascular Medicine published in the journal Frontiers in Cardiovascular Medicine online searches for GLP-1 agonists and prescriptions are increasing in tandem.
Patients may wonder which weight loss medication is the most powerful or effective. Answer: It's complicated. It's not always simple to decide which medication is best for an individual. It is important to stay abreast of the market's rapid changes.
BMI is the first step in determining if someone is a good candidate for weight-loss medications. The majority of medications are prescribed to people with a body mass index (BMI) of 30 or higher, or for those who have health conditions related to weight.
In November 2023, Zepbound became available for adults who have a BMI greater than 30. In each case, the doctor should talk to the patient about his or her current health problems and any other medications. Cost and side effects of the medication will also influence your decision.
Semaglutide (liraglutide), orlistat, and liraglutide are all approved by the FDA for children 12 years and older. All the medications listed here are contraindicated during pregnancy.
Weight loss drugs have been available for many years. However, new products are introduced regularly. Weight loss medications that are commonly prescribed include:
Wegovy is the brand name of semaglutide. It's a GLP-1 agonist. FDA approved the drug in 2021. It is approved for adults and children over 12 years of age with obesity (BMI 30 for adults; BMI 95th percentile based on age and gender for children), or for some adults who are overweight (BMI 27) and have weight-related health problems. To reach the 2.4mg dosage, the dose must be gradually increased over 16-20 weeks. This can reduce side effects such as gastrointestinal symptoms, headaches, dizziness and fatigue.
Ozempic, a medication approved for type 2 diabetes, is the same as Ozempic.
Mounjaro was the name of the drug that had been approved for treating type 2 diabetes. Zepbound is approved for treating obesity in adults who have a BMI greater than 30.
It works as a GLP-1 receptor agonist, and also as a GIP-receptor agonist. Like semaglutide it reduces appetite. It can also be administered by injection.
Liraglutide, a daily injectable medicine, works on hormones in the gut to send signals to brain that make patients feel fuller faster and reduce hunger signals. The doses range from 0.6 mg up to 3 mg per day. Some patients can lose up to 10% of their body weight when taking liraglutide at higher doses.
The most common side effects are nausea, diarrhea and constipation. Other symptoms include headaches, nausea, fatigue, abdominal pain, dizziness and increased lipase. Patients with a personal or familial history of medullary carcinoma or Multiple Endocrine Neoplasia Syndrome type 2 are contraindicated.
Phentermine, the oldest and most popular weight loss drug, is also one of the most effective. It was initially used to kick-start weight-loss, but newer medical guidelines now include it in long-term treatment. Phentermine can cause some patients to lose 5% of their weight.
In the US, phentermine HCl is available only in strength of 15 mg or 30 mg. Some of the side effects are headaches, insomnia, insomniac high blood pressure and rapid or irregular heartbeat.
There may be interactions within 14 days of using monoamine oxidase inhibitors (MAO), sympathomimetics or alcohol.
Combining Topiramate with Phentermine can help reduce appetite and cravings. Combining two drugs can increase their efficacy.
This weight loss medication is suitable for adults with obesity and migraines. Patients may lose between 5-10% of their body weight.
The weight loss pill can be discontinued gradually if a weight loss of more than 5% is not achieved within 12 weeks after the maximum dosage.
The daily doses range from 3.75 mg/23mg to 15mg/92mg. Other side effects include dizziness and altered taste. Contraindications to this drug include uncontrolled high blood pressure and coronary heart disease, hyperthyroidism and glaucoma.
Naltrexone and bupropion combine an opioid receptor antagonist and an antidepressant in order to influence the pleasure-reward regions of the brain, and reduce cravings and appetite. Some patients can lose between 5-10% body weight.
Begin with one 8/90mg tablet per day and increase the dose to four tablets daily. Most common side effects are nausea, constipation headache, vomiting dizziness insomnia diarrhea. Patients with seizure disorders or those who take opioids to treat chronic pain should not receive this medication.
Setmelanotide, a melanocortin-4 agonist, is indicated to manage chronic weight in adults and children aged 6 and older who are obese due to one or more rare genetic disorders.
Genetic testing must confirm the condition by demonstrating variants of POMC, LEPR, or PCSK1 genes that are interpreted either as pathogenic or likely pathogenic or as a variant with uncertain significance (VUS).
Orlistat, a lipase inhibitor that is available in capsule form, works by blocking an enzyme that breaks down the fats that are consumed. It works by blocking the enzyme that breaks down dietary fats.
Undigested fat then passes through the body. It can be used in conjunction with reduced-calorie dieting and to reduce weight gain.
Some patients can lose up to 5% of body weight. The dosage is one 120mg capsule taken three times daily with each meal that contains fat (during the meal or up to an hour after).
A 60mg capsule is available over the counter with every meal that contains fat. Orlistat is associated with oily discharges from the rectum and flatus, as well as increased defecation and fecal indigestion.
Plenity, a medical device and not a drug, was FDA cleared in 2019 for individuals with a BMI between 24 and 40. Media attention has increased since the rise in popularity of GLP-1 receptor antagonists.
The capsule releases a super-absorbent, biodegradable hydrogel in the stomach. The gel increases satiety and allows the user to eat less. In real-life studies, the average weight loss is 9%.
The latest edition of Obesity Medicine Association Obesity Agorithm(r),, contains more detailed information on each of these weight loss medications.
In the next few years, there will be more weight loss drugs on the market due to the rising obesity rate and the fervent demand from consumers.
Lilly is developing orforglipron as an oral GLP-1 antagonist. Retatrutide is another injectable that targets GLP-1 as well as GIP and glucagon. Pfizer has also developed two GLP-1 inhibitors that are available as pills. Amgen, meanwhile, is testing a drug that is both GLP-1 receptor antagonist and GIP receptor agonist, instead of a dual receptor like semaglutide.
Researchers are still looking for hormones, like peptide YY that can be used to treat obesity.
Interviewed by Endocrine News in 2021, Robert Kushner, MD, a professor at the Northwestern University Feinberg School of Medicine, lauded "the new direction that we are going in obesity treatment, treating it more as an endocrine disease, treating it hormonally..."--giving patients and providers different options to choose the drug that will be the most useful.
Monoclonal antibody drug development is another "hot" area in the field of medicine. This includes obesity. The monoclonal antibodies bimagrumab are being studied for infusions to increase muscle mass and decrease fat.
As more options become available, doctors can personalize treatment by matching patients with the best medications.
FDA-approved antiobesity medication (AOMs), which target specific physiology in order to improve the condition, are evidence-based and safe therapies. They are most effective when used as part a comprehensive treatment program. Weight loss depends on a number of factors, including the medications taken, health status, and individual characteristics.
Some drugs have been removed from the market due to their ineffectiveness and safety concerns.
Clinical studies have shown that semaglutide can cause a significant weight loss. In a study conducted in 2022, 175 participants showed a weight loss of 5.9% after three months and 10.9% after six months. In a larger study, published in New England Journal of Medicine, the average weight loss was even higher at 14.9%. Semaglutide has some drawbacks, including its high cost, side-effects, and long-term or indefinite treatment.
A person may experience better results from one medication than another, as with any obesity treatment. In partnership with their doctor each person should find the best combination of treatments for them.
In 2022 the American Gastroenterological Association will release recommendations on weight loss medication for patients with obesity that do not respond to lifestyle changes alone. They listed four options as first-line:
Also recommended were phentermine, and diethylpropion. These recommendations were made prior to the approval of Zepbound.
These drugs suppress hunger and cravings by regulating hormones within the brain, digestive tract, and adipose tissues.
Subcutaneous injections are used for some medications and oral administration is the case for others. Patients often refer to GLP-1 RAs when they ask about weight loss pills vs. subcutaneous injections. In May 2023 data released by Novo Nordisk, Pfizer and Novo Nordisk separately showed that injections and pills are almost equally effective.
Many medications can be obesogenic, or cause weight gain. Some individuals may experience variable weight gain from the following medications.
Treatment plans for obesity may include medications, diets, exercises and/or surgeries. Weight loss medications are most effective when combined with a healthy diet and regular exercise. Even if a patient engages in exercise or other lifestyle changes, medications can still help reduce hunger, cravings and maintain metabolic health.
Some weight-management medications are intended for short-term usage, while others are meant for long-term. Some are approved by FDA for as long as 12 weeks.
Those approved by the FDA for long-term use include orlistat (Xenical, Alli), phentermine-topiramate (Qsymia), naltrexone-bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy, Ozempic), and tirzepatide (Zepbound, Mounjaro).
Some of these drugs require a lengthy ramp-up phase -- up to five months -- before reaching the full dose. Remember that obesity is not a cure.
The GLP-1 receptor antagonists (RAs) have been gaining a lot attention, but they are just the latest in an evolving line of weight loss drugs. A 2022 article from Life Science describes.
"...as new physiological mechanisms of weight gain were discovered, drugs targeting newly-discovered receptors or enzymes with improved safety profiles have been introduced. These drugs have fewer psychological side effects and have better safety profiles. Drugs that target hunger or satiation signaling are also being actively studied, and physicians have begun to adopt them. Researchers have evaluated the effectiveness of drugs that target tissues such as adipose or muscle tissue to promote weight loss. However, nothing has been implemented into clinical practice.
There will be new candidates developed and some of them will reach the market.
Some weight loss medications are more affordable than others, because they have been around for longer and have generic alternatives. GLP-1 RAs can be expensive. According to the Kaiser Family Foundation, Wegovy's estimated annual net price is $13,600. GoodRx reports that phentermine is available for as low as $10 .
Insurance coverage can vary and affect the decision of many patients to take weight loss medication. Medicare doesn't cover weight loss medications.
AOMs can counteract the effects of metabolic adaption and prevent weight gain. The body adapts to a weight loss by increasing hunger hormones, decreasing satiety and resting metabolism. This can lead to weight gain. If the patient has achieved clinically significant weight loss with anti-obesity medication and both the clinician and the patient believe that the medication helps to prevent weight gain, then the medication should continue for weight loss maintenance.
Alli (Orlistat) is the only weight loss medicine approved by FDA for over-the-counter use. Supplements are also considered to be other over-the counter products. These products are not regulated or studied by the FDA to prove their safety and efficacy.
A healthcare professional can monitor side effects and progress of a patient when they are prescribed prescription medication. This can lead to dosage adjustments and alternative medications, if they seem like a better match for the patient.
Weight-negative antidepressants (cause weight loss) are rare.
Antidepressants can be categorized into SSRIs, SNRIs, tricyclics antidepressants (including MAO inhibitors), monoamine oxidase (MAO) inhibitors and others. Each of these medications can lead to weight gain.
Paroxetine is the SSRI with the most weight gain. Other SSRIs such as Citalopram, Escitalopram, Fluoxetine, Prozac, and Sertraline have variable effects on the weight. Some do not show weight gains until six months after use.
Amitriptyline is a weight-positive medication in the tricyclic category of antidepressants. The effects of Nortriptyline and Protriptyline on weight are variable.
Bupropion, an aminoketone (Wellbutrin), is prescribed to help with weight loss as well as to treat depression. Antidepressants are not the same for everyone.
The following FDA-approved medications suppress appetite: Tirzepatide (Zepbound), Liraglutide (Saxenda), Naltrexone-Bupropion (Contrave), Phentermine-Topiramate (Qysmia), as well as these stimulants: benzphetamine (Didrex(tm)), diethylpropion (Tenuate(tm)), phentermine (Adipex-P, ProFast), and phendimetrazine. Each medicine affects appetite differently.
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