Top Weight Loss Medications

The pharmacological treatment of obesity is a fast-changing landscape, and care providers must strive continuously to stay current. Before 2012, there were few weight loss medications approved by the FDA. The top obesity medications (OMs) at that time were phentermine, marketed as Adipex-P, and orlistat, marketed as Xenical and Alli.

In 2021, attention to obesity medications exploded in popularity and media attention with the approval of semaglutide for obesity treatment under the brand name Wegovy. Next came a dual GLP-1/GIP receptor agonist, tirzepatide, marketed under the brand name Zepbound, which was approved for obesity in 2023. Both medications are administered by injection. The end of 2025 brought the first oral GLP-1 RA medication for obesity treatment, a pill form of Wegovy.

A study from FAIR Health published in May 2025 reports that more than 2% of U.S. adults took a GLP-1 for weight loss in 2024. (Many more take them for other indications.) According to the Kaiser Family Foundation, public awareness has ramped up, with 32% of adults now saying they have heard “a lot” about these drugs.

With a growing selection of weight loss medications available, patients may ask what the strongest or most effective weight loss prescription medication is, and which one is best for them. The answer is complicated, newer is not always better, and not everyone needs the most potent medication choice.

Criteria for Weight Loss Medication Prescriptions #

Determining whether someone is a candidate for weight loss medications begins with BMI. Most medications are prescribed for someone with a BMI of 30 or greater, or a BMI of 27 or greater if the person has weight-related health conditions.

For each individual case, the doctor and patient should discuss the patient’s current health issues, other medications, and family medical history. The medication’s cost and side effects will also affect the decision.

Other considerations when prescribing obesity medications (OMs) include:

• The amount of weight reduction and duration will vary by patient.
• The average weight loss varies from 5% to 21%, with some people losing more and some people losing less. Some people do not lose weight with obesity medications.
• If weight loss of at least 5% is not achieved within 12-16 weeks at the maximum tolerated dose, then an alternative OM should be considered.
• Most people regain weight if OMs are discontinued. Consequently, a long-term approach to obesity treatment is recommended.

While some weight loss medications are FDA-approved only for adults, some—including injectable semaglutide and liraglutide—are approved for children 12 and older with a BMI >/= 95^th percentile. All of the medications discussed here are contraindicated for pregnancy.

Currently Available Weight Loss Medications #

Some weight loss medications have been on the market for many years, and new ones emerge frequently. It can be easy to overlook first-generation OMs, but these may be appropriate for some patients, especially when cost is a factor. Commonly prescribed weight loss medications include:

Semaglutide (Wegovy, Ozempic)

Wegovy is a brand name for semaglutide, a GLP-1 receptor agonist. It was FDA-approved for obesity treatment in 2021. It is administered as an injection and approved for use in adults and children aged 12 years or more with obesity (BMI ≥30 for adults, BMI ≥ 95th percentile for age and sex for children) or some adults with excess weight (BMI ≥27) who also have weight-related medical problems. The dose is increased every four weeks as tolerated up to a maximum dose of 2.4 mg. This progression can be slowed to help alleviate side effects, which include gastrointestinal symptoms, headache, dizziness, and fatigue. 

In December 2025, an oral version of semaglutide, Wegovy Pill, received FDA approval for the treatment of obesity. In the OASIS clinical trial, the oral version of semaglutide was initiated with a 3 mg dose which was titrated every four weeks to 7mg, 14mg, then a final dose of 25mg, however the initial dose of the Wegovy Pill will be 1.5mg. Oral semaglutide should be taken on an empty stomach, and patients must wait 30 minutes before eating after taking the medication. In clinical studies, the side effect profile of the oral version was similar to injectable semaglutide. More information on prescribing details will follow as they become available.

Because obesity is a chronic disease, obesity medications should be used long term in combination with a healthy diet and exercise. Semaglutide is also approved to treat type 2 diabetes under the brand name Ozempic which may be a more familiar name to some patients. 

Tirzepatide (Zepbound, Mounjaro)

Zepbound is approved to treat obesity in adults with a BMI of 30 or greater, or a BMI of 27 or greater if the person has weight-related health conditions. It is a dual GLP-1 and GIP receptor agonist. Like semaglutide, it works by reducing appetite and is meant to be used in combination with diet and exercise to lose weight. It is also administered as an injection.

Tirzepatide was previously approved to treat type 2 diabetes as Mounjaro, and it goes by that name only in some countries.

Liraglutide (Saxenda)

Liraglutide is a daily injectable medication that mimics endogenous GLP-1, which is produced in the gut and signals the brain to decrease hunger and create a feeling of fullness with smaller meals. Doses start at 0.6 mg and are titrated up to 3 mg a day as needed. Some patients may lose 5–10% of body weight, especially with the higher dose of liraglutide. Unlike Wegovy and Zepbound, it is injected once daily instead of weekly.

Liraglutide is also approved for type 2 diabetes, under the brand name Victoza.

Side effects are similar to other GLP-1 RAs which include nausea, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, and renal insufficiency. It is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.

Phentermine (Adipex, Suprenza, Lomaira)

Phentermine is the oldest and most widely used weight loss medication. It is FDA approved for short-term use but is widely accepted as a long-term option for obesity treatment among obesity medicine prescribers. Average weight loss on phentermine is 5 to 10% of body weight. 

In the U.S., phentermine extended release is available as a 15 mg or 30 mg capsule, or a 37.5 mg scored tablet. A short-acting form of phentermine is available as an 8mg scored tablet used up to three times a day and sold under the brand name Lomaira. Side effects include headache, overstimulation, high blood pressure, insomnia, rapid or irregular heart rate, and tremor. 

Interactions may occur during or within 14 days following the use of monoamine oxidase (MAO) inhibitors, sympathomimetics, alcohol, adrenergic neuron-blocking drugs, and possibly some anesthetic agents. Phentermine should be stopped seven days before planned general anesthesia.

Phentermine-topiramate (Qsymia)

Topiramate, long used for seizure disorders and chronic migraine headache, was approved for obesity treatment in an extended-release combination with phentermine in 2012. Combining the two drugs provides a synergistic improvement in efficacy. A generic version of Qsymia became available in 2025.

Adults with migraines and obesity are good candidates for this weight-loss medication. Some patients may lose an average of 5–10% of body weight. If more than 5% weight loss is not achieved after 12 weeks of the maximum dose, the weight loss pill should be gradually discontinued.

Daily doses with four strengths start at 3.75 mg/23 mg to 15 mg/92 mg. Side effects include abnormal sensations, dizziness, altered taste, insomnia, constipation, and dry mouth. Contraindications include uncontrolled hypertension and coronary artery disease, hyperthyroidism, glaucoma, and sensitivity to stimulants.

Naltrexone-bupropion (Contrave)

Naltrexone-bupropion combines an opioid receptor antagonist with an antidepressant to affect the pleasure-reward areas of the brain and thereby decrease cravings and appetite. Patients lose an average of 5–10% of body weight on this extended-release combination medication.

Dosing recommendations begin with a daily dose of one 8/90 mg tablet and gradually increase on a weekly basis to a maximum of two tablets twice a day. The most common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. This medication should not be prescribed to a patient who has a seizure disorder or who takes opioids for chronic pain.

Orlistat (Xenical and Alli)

Orlistat is a lipase inhibitor that comes in capsule form. It works by blocking a digestive enzyme that breaks down fats in the GI tract, thus inhibiting the absorption of dietary fats.

Undigested fat is then excreted in the feces. It is intended for use with a reduced-calorie diet and is also indicated to reduce the risk of weight regain.

Some patients may lose about 5% of their body weight. Dosage is one 120 mg capsule three times a day with each main meal containing fat (during or up to one hour after the meal).

An over-the-counter formulation is available at 60 mg capsules with each fat-containing meal. The most common adverse reactions to orlistat are oily discharge from the rectum, flatus with discharge, increased defecation, and fecal incontinence.

Setmelanotide (Imcivree)

Setmelanotide is a melanocortin-4 receptor agonist indicated for chronic weight management in adult and pediatric patients six years and older, with obesity due to certain rare genetic disorders. It is being studied for use in patients with acquired hypothalamic obesity.

The condition must be confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of a variant of uncertain significance (VUS).

More detailed information about each of the above weight loss medications can be found in the latest edition of Obesity Medicine Association’s Obesity Algorithm®.

Upcoming Weight Loss Medications #

Researchers continue to study hormones that play a role in appetite and for other ways to target obesity and obesity-related diseases with medication. Those of targets center around nutrient-sensing hormones including GLP-1, GIP, glucagon, amylin, peptide tyrosine-tyrosine (PYY) and cholecystokinin (CCK).

With fervent consumer demand for weight loss medications, combined with rising obesity rates, more medications are bound for the market in the coming years. The pharmaceutical platform Ozmosi predicts one to two GLP-1 launches annually starting in 2026. In May 2025, they reported 39 new GLP-1 RA related medications in development.

Lilly is developing several new obesity medications. Orforglipron, is a small-molecule nonpeptide oral GLP-1 inhibitor that completed a phase 3 clinical trial in 2025. Small-molecule nonpeptide GLP-1 RAs are more stable in the stomach and can be taken with food. Phase 3 results showed an 11.2% weight loss at the 36 mg dose at 72 weeks. 

Another promising Lilly product in the pipeline is retatrutide. This injectable triple receptor agonist targets GLP-1, GIP, and glucagon. There are seven phase 3 clinical trials in progress. At this writing, only TRIUMPH-4 has been reported by the company. The study included patients with obesity and knee osteoarthritis with trial endpoints examining weight loss and reduction in knee pain. In this trial, participants lost up to 28.7% of body weight at 68 weeks. Other trials will examine the effect of retatrutide on obstructive sleep apnea, chronic kidney disease, type 2 diabetes, major adverse cardiac events, and low back pain in addition to weight loss with expected readouts in 2026 and 2027. We are likely to continue to see clinical trials include treatment of adiposity-related diseases as a component of obesity medication investigations.

A combination of an amylin analog, cagrilintide, and semaglutide known as CargiSema, is a single weekly injection under development by Novo Nordisk, with phase 3a results published in 2025. The results of the 68-week trial identified a mean weight loss of 20.4% with 19.3% of participants achieving weight loss of 30% or more. Another amylin and GLP-1 agonist pair being developed by Novo Nordisk is amycretin. This dual agonist comes in both oral and weekly subcutaneous injection. Phase 2 results for a weekly injection found a mean 24.3% weight loss at 36 weeks with the 60mg dose. Both oral and injectable forms are reportedly moving into phase 3 studies. Eli Lilly completed a 48 week phase 2 trial on a selective amylin agonist, eloralintide. Weight loss ranged from 9.5% at 1mg to 16.4% at the 9mg dose.

Obesity medications targeting glucagon and GLP-1 represent another dual agonist target that benefit both weight and cardiometabolic health. Glucagon receptors are mainly expressed in the liver making it an attractive target for metabolic dysfunction-associated steatotic liver disease and steatohepatitis, MASLD and MASH. There are several molecules in development with particular interest in mazdutide and survodutide. Mazdutide has been approved for use in China where it showed a 14.8% weight loss, decrease in waist circumference and reduction in liver fat in that population. Survodutide completed separate phase 2 trials in 2024 examining individuals with obesity and those with biopsy confirmed MASH. In a 46-week obesity treatment trial, mean weight loss was 14.9% at the highest dose. In the steatotic liver disease trail, improvement in MASH ranged from 43% to 62% depending on dose with significant reductions in liver fat. Phase 3 trials for steatotic liver disease and weight loss are underway.

Amgen is developing maridebart cafraglutide, known as MariTide, a long-acting peptide-antibody conjugate designed to increase GLP-1 receptor activity while inhibiting GIP receptor activity. The once-monthly injection entered phase 3 clinical trials for weight loss and type 2 diabetes in March 2025. Future studies will investigate the effect of MariTide on cardiovascular disease, heart failure, chronic kidney disease, and obstructive sleep apnea. In a phase 2 study, the medication showed up to 20% average weight loss at 52 weeks for people with obesity or overweight without diabetes and 17% for those with overweight/obesity and type 2 diabetes.

With more obesity medication options available along with indications for treatment of obesity-related diseases, doctors will be increasingly able to personalize treatments. For more information on other emerging options, enroll in OMA’s course on Investigational Anti-Obesity Drugs in the Pipeline.

Frequently Asked Questions About Weight Loss Medications #

How effective are weight loss medications?

FDA-approved obesity medications (OMs) are safe, evidence-based therapies that target specific physiology to improve the disease and are most effective when used as part of a comprehensive treatment plan. The amount of weight a person loses depends on the medication they take, their overall health, and other individual factors.

Even as the range of weight loss medications has expanded, some drugs have been withdrawn based on their lack of efficacy as well as safety concerns.

What is the strongest weight loss prescription medication?

Based on the latest clinical trials and real-world data, tirzepatide (Zepbound) currently stands out as the most effective FDA-approved prescription medication for weight loss.

In the SURMOUNT-1 trial, adults with obesity or overweight (without diabetes) taking tirzepatide achieved up to 22.5% average body weight reduction at 72 weeks. This surpasses the weight loss seen with semaglutide (Wegovy), which showed 14.9% average loss in the pivotal STEP 1 trial over a similar timeframe. In a head-to-head study of the two agents sponsored by Eli Lilly, makers of tirzepatide, found a 20.2% weight loss with tirzepatide compared to a 13.7% weight loss with semaglutide.

For a comparison of individual clinical trial results:

• Tirzepatide (Zepbound): Up to 22.5% average weight loss
• Semaglutide (Wegovy injectable): Up to 14.9% average weight loss
• Semaglutide (Wegovy Pill): Up to 16.6% average weight loss
• Liraglutide (Saxenda): ~8% average weight loss
• Phentermine-topiramate (Qsymia): 7–11% weight loss depending on dose
• Naltrexone-bupropion (Contrave): ~5–9% average weight loss

These commonly used medications for obesity decrease appetite, improve satiety, and support metabolic health. 

Are obesity medications indicated for the treatment of other health conditions?

The GLP-1 and related compounds are indicated for the treatment of type 2 diabetes. In addition, Wegovy injectable and pill have an indication to reduce cardiovascular risk in patients with known CVD and overweight/obesity. The injectable form also has an indication to treat patients with noncirrhotic metabolic dysfunction-associated steatohepatitis with moderate to advances fibrosis (stage F2 or F3). Zepbound has an indication for the treatment of moderate to severe obstructive sleep apnea in adults with obesity. Future obesity medications under investigation typically include the treatment of obesity-related diseases in their outcomes.

How do weight loss medications work?

Obesity medication targets the biologic systems that regulate appetite, satiety, energy balance, and nutrient handling. They work primarily by modifying neurohormonal pathways in the brain. Obesity medication may also impact the reward systems in the brain to reduce cravings and lessen food noise.

Some medications are administered orally, and others are given as subcutaneous injections. Patients who are less comfortable with injections may be good candidates for oral medications. In 2025, semaglutide became the first oral GLP-1 receptor agonist to be approved for obesity treatment.

Are there medications that can cause weight gain?

There are many medications that can be obesogenic or cause weight gain. The following medications can potentially cause variable weight gain in some individuals.

• Some beta-blockers and calcium channel blockers
• Anti-diabetes medications such as insulins, sulfonylureas, thiazolidinediones, and meglitinides
• Hormone therapies such as glucocorticoids and injectable progestins
• Anti-seizure medications, including carbamazepine, gabapentin, valproate, and pregabalin
• A wide variety of different antidepressants
• Some mood stabilizers
• Migraine medications such as amitriptyline and paroxetine
• Some antipsychotics
• Chemotherapeutic and anti-inflammatory agents

How should weight loss medications be used in conjunction with other forms of treatment?

A medical treatment plan for obesity should comprise a comprehensive approach including dietary intervention, a physical activity plan, behavioral modification, and pharmacotherapy. All of the studies done to evaluate obesity medications included a dietary plan, regular physical activity, and behavioral modification. Prescribing obesity medication in the absence of lifestyle modification increases the risk of muscle loss and nutritional deficiencies. By combining a healthy eating plan and regular physical activity, including strength training, patients can improve weight loss and metabolic health outcomes as well as develop healthy habits that can provide long-term benefits. 

How long do weight-loss medications need to be taken?

Obesity is considered a chronic disease. As with other chronic diseases, treatment should be viewed as long-term, similar to diabetes and hypertension. The older, sympathomimetic medications, like phentermine, were only approved for short-term use, though many clinicians experienced in obesity care use them for longer than 12 weeks. The newer obesity medications approved since 2012 are indicated for long-term use. 

Obesity medications approved by the FDA for long-term use include orlistat (Xenical, Alli), phentermine-topiramate ER (Qsymia), naltrexone-bupropion ER (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound). Numerous studies have shown that stopping obesity medications after weight loss results in weight regain. This should not be viewed as a failure of the medication to work, but as a consequence of weight loss associated metabolic adaptation and hormonal response that results in slower metabolism and increased hunger.

How have options in weight loss medications changed in recent years?

While GLP-1s have grabbed a lot of headlines, they are only the latest in a long history of evolving weight loss medications. A 2022 article in Life Science explains:

“…as more physiological mechanisms for weight gain have been unearthed, drugs targeting newly discovered receptors and/or enzymes have been introduced with improved safety profiles and fewer psychological adverse events. Additionally, drugs targeting hunger or satiety signaling have been actively studied and have shown increased adoption by physicians. Studies have also evaluated drugs that target metabolic tissues—such as adipose tissue or muscle—to promote weight loss; however, to date, nothing has carried on into clinical practice.”

There is a wide range of obesity medications under investigation with different physiologic targets. In the future, providers will have a wider range of obesity treatment options. Hopefully, affordability will improve through lower cost and better insurance coverage.

How do the different categories of weight loss medications compare in terms of cost?

As with many medications, some weight loss drugs have been on the market longer, have generic alternatives, and tend to be more affordable. In 2025, the phentermine-topiramate ER (Qsymia) combination became available in generic form. The GLP-1 related medications are particularly costly. The Kaiser Family Foundation estimates the annual net retail price of Wegovy at $13,600. However, both Eli Lilly and Novo Nordisk have direct purchase options that greatly reduce the monthly price for patients that do not have insurance coverage. According to GoodRx, phentermine can be had for as little as $10.

Direct Purchase Options #

Both Wegovy and Zepbound are now available for eligible cash-paying patients—regardless of dose strength:

• NovoCare Pharmacy offers Wegovy (semaglutide) in all dose strengths available via home delivery and in most pharmacies to uninsured or commercially insured individuals without obesity drug coverage.
• LillyDirect provides Zepbound (tirzepatide) single-dose vial access for home delivery in all available doses to individuals without insurance coverage for obesity medications. 

These programs apply only to self-pay patients and are not covered by insurance. They do not count toward deductibles or out-of-pocket maximums.

Insurance coverage varies and will affect many patients’ choices about going on weight loss medications. Currently, Medicare does not cover obesity medications.

How do they affect weight regain?

Obesity medications may counter the effects of metabolic adaptation and prevent weight regain. After weight reduction, the body metabolically adapts, often causing an increase in hunger hormones, a decrease in satiety hormones, and a reduced resting metabolic rate, all of which can contribute to weight regain. If the patient achieves clinically meaningful weight reduction with obesity medications and if the clinician and patient feel that the medication is helping to avoid weight regain, then a weight reduction plateau should not be considered a point where medication should be discontinued, but rather the medication should be continued for weight reduction maintenance.

What are the differences between OTC and prescription weight loss medications?

The only over-the-counter medicine for weight loss currently approved by the FDA is Alli (orlistat). Other over-the-counter products are considered supplements. They are not regulated by the FDA and do not have proper studies to confirm their safety and effectiveness. Some OTC supplements promoted for weight loss have serious potential side effects. The safety and efficacy of these medications should be discussed with a knowledgeable health professional before taking them, especially if you have underlying health conditions.

With prescription medications, a healthcare professional can weigh all factors affecting the patient’s lifestyle and BMI and monitor progress and side effects. This relationship can allow for dosage adjustments or alternative medications if one seems like a better fit for the patient.

What is the connection between antidepressant medication and weight loss?

Many antidepressants are weight-positive (cause weight gain), some are weight-neutral, and at least one is weight-negative (causes weight loss).

Antidepressants are broken down into categories: selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase inhibitors (MAO inhibitors), and others.

In the SSRI group, paroxetine shows the highest associated weight gain. Other SSRIs, including citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), and sertraline (Zoloft), have variable effects on weight, and some do not show weight gain until after six months of use.

Weight-positive medications in the tricyclic antidepressant category include amitriptyline, doxepin, and imipramine. Desipramine, nortriptyline, and protriptyline have variable effects on weight.

Bupropion (Wellbutrin), an aminoketone, is considered weight-negative and is prescribed both to assist in weight loss and to treat depression.

What qualifies someone for weight loss medication?

The guidelines for pharmacotherapy for obesity treatment recommendations are based on BMI. Individuals qualify with a BMI ≥ 30 or a BMI ≥ 27 with a weight-related health conditions such as type 2 diabetes, hypertension, dyslipidemia, and obstructive sleep apnea. Other conditions may be covered as well depending on individual insurance company policies. None are approved for use in someone who is pregnant.

What are “counterfeit” GLP-1s?

Some online healthcare providers claim to sell Ozempic, Wegovy, or Zepbound at reduced prices. However, the FDA warns against buying medications from any source other than a state-licensed pharmacy. In April 2025, they banned the sale of “counterfeit” semaglutide and tirzepatide. These medications are not made or packaged by the original manufacturers. Instead, they are compounded medications. They may contain the same active ingredient (e.g., semaglutide or tirzepatide) but—the FDA warns—“could contain the wrong ingredients, contain too little, too much, or no active ingredient at all or other harmful ingredients…”

Are compounded weight loss medications safe and effective?

Compounded versions of medications are made by compounding pharmacies, often to tailor a medication to specific patient needs, like an allergy to an inactive ingredient. Compounded medications are not FDA-approved. For about two years, traditional 503A compounding pharmacies and 503B outsourcing facilities were permitted by the FDA to make compounded semaglutide and tirzepatide under the exceptions for drug shortages. The 503A pharmacies are state-licensed facilities that follow USP guidelines to prepare customized medications for specific patients. The 503B outsourcing facilities produce compounded drugs in bulk and are registered with the FDA. They are subject to stricter FDA oversight than the 503A pharmacies. 

In the spring of 2025, both tirzepatide and semaglutide came off the drug shortage list ending the legitimate use of compounded agents in the absence of specific exceptions. With the high demand for these high potency obesity medications, there has been an explosion of illicit sources of compounded semaglutide and tirzepatide. The FDA has received 605 reports of adverse events associated with compounded semaglutide and 545 reports of adverse events associated with compounded tirzepatide (as of July 31, 2025). Patients and doctors should always discuss the potential risks and potential benefits as they relate to that patient’s unique situation. The OMA has published a position statement on the use of compounded medications.

Are you seeking obesity treatment? Find an obesity medicine specialist near you who can assist in finding the best weight loss medications for you.

Weight Loss Medications At a Glance #

Drug name	Brand name(s)	Approved for	How it’s administered	Frequency
Semaglutide (injectable)	Wegovy	Adults, Children 12+	Subcutaneous Injection	Once weekly
Semaglutide (oral)	Wegovy Pill	Adults	Oral	Once daily
Tirzepatide	Zepbound	Adults	Injection	Once weekly
Liraglutide	Saxenda	Adults, Children 12+	Injection	Once daily
Phentermine	Adipex, Suprenza, Lomaira	Age 17+	Tablet, capsule, or ODT	Daily (Lomaira 3x/day)
Phentermine-topiramate ER	Qsymia	Adults, Children 12+	Capsule	Once daily
Naltrexone-bupropion ER	Contrave	Adults	Tablet	Once or twice daily
Orlistat	Xenical, Alli	Adults, Children 12+	Capsule	3x/day
Setmelanotide	Imcivree	Adults, Children 6+ (only with certain rare genetic disorders)	Injection	Once daily