FDA-Approved Weight Loss Drugs Compared: Results, Costs, Withdrawals

As of 2026, the FDA-approved weight loss drugs are Zepbound (tirzepatide), the Wegovy injection and the Wegovy pill (semaglutide), Foundayo (orforglipron), Qsymia (phentermine/topiramate), Contrave (naltrexone/bupropion), Saxenda (liraglutide), orlistat (Xenical, with a lower-dose version, Alli, sold over the counter), phentermine (Adipex-P, Lomaira), and Imcivree (setmelanotide) for rare genetic and hypothalamic forms of obesity. Average weight loss in the key trials ranges from 3.7% for Contrave in a population with diabetes to 20.2% for Zepbound, but those figures come from separate trials; SURMOUNT-5 is a head-to-head trial that compared tirzepatide against semaglutide directly ^[1][12]. On cost, Zepbound carries a list price of roughly $1,086 per month, Saxenda’s cash price without coverage is $1,686 per fill, and phentermine averaged $15 per fill out of pocket in 2025 ^[2][19]. Three withdrawal actions have pulled weight loss drugs from the US market: fenfluramine and dexfenfluramine in 1997, sibutramine (Meridia) in 2010, and lorcaserin (Belviq) in 2020 ^[24][25][26].

Which drug fits a particular person is a prescriber’s decision, based on health conditions, other medications, tolerance and cost. The Obesity Association’s 2026 guideline, covered below, matches drugs to specific health conditions rather than ranking them outright ^[15][27].

How should you compare weight loss numbers across these drugs?

Each headline percentage comes from a trial with its own length, population and analysis method, so cross-trial figures are not head-to-head results ^{[1][6][30][31]}.

SURMOUNT-5 ran 72 weeks, was open-label (participants knew which drug they received), and compared tirzepatide against semaglutide in adults with obesity or overweight with at least one weight-related problem and no diabetes ^[1]. STEP 1 ran 68 weeks, was double-blind, and randomly assigned 1,961 adults in a 2:1 ratio to semaglutide 2.4 mg or placebo ^[30]. OASIS 4 tested oral semaglutide 25 mg with a primary endpoint at week 64 and randomized 307 people ^[31]. EQUIP ran 56 weeks in 1,267 adults with a BMI of 35 or higher and used an ITT-LOCF analysis, which carries each participant’s last weight forward if they leave the trial ^[6][7].

How much weight does Zepbound produce?

Zepbound is a dual GIP and GLP-1 receptor agonist given once weekly ^[1]. In SURMOUNT-5, a head-to-head trial of tirzepatide versus semaglutide, participants on Zepbound lost an average of 20.2% of body weight at 72 weeks, versus 13.7% on Wegovy — an average of 50.3 lb versus 33.1 lb ^[1].

More participants on Zepbound hit each weight loss target: 48.4% versus 27.3% lost at least 20%, and 31.6% versus 16.1% lost at least 25% ^[1]. Average waist reduction was 18.4 cm versus 13.0 cm ^[1]. Adverse events were mostly gastrointestinal and mild to moderate; 6.1% of Zepbound participants stopped for adverse events versus 8.0% on Wegovy, though the trial was not designed to compare safety between the two ^[1].

What does Zepbound cost?

Starting December 1, 2025, cash-paying patients with a prescription can buy single-dose Zepbound vials on LillyDirect for $299 per month at the 2.5 mg dose, $399 at 5 mg, and $449 at higher doses, down from a previous range of $349 to $499 ^[2][13]. Zepbound carries a list price of roughly $1,086 per month ^[2]. Among people filling prescriptions in 2025, the average out-of-pocket cost per Zepbound fill was $110, including both insured copays and cash payments ^[19].

How much weight does the Wegovy injection produce, and what does it cost?

In STEP 1, adults on once-weekly semaglutide 2.4 mg lost an average of 14.9% of body weight at 68 weeks, versus 2.4% on placebo, a treatment difference of 12.4 percentage points ^[30]. Threshold results: 86.4% of the semaglutide group lost at least 5%, 69.1% lost at least 10%, and 50.5% lost at least 15% ^[30].

A higher-dose injection, Wegovy HD 7.2 mg, produced about 21% average weight loss over 72 weeks and was approved in March 2026 ^[5].

On NovoCare self-pay pricing, the two lowest pen doses (0.25 mg and 0.5 mg) cost $199 per month for the first two fills through December 31, 2026, then $349 per month; Wegovy HD 7.2 mg costs $399 per month ^[3]. Commercially insured patients may pay as little as $25 per month for up to 3 months, with maximum savings of $100 per month; government beneficiaries are excluded from that offer ^[3].

What do the GLP-1 pills deliver?

There are now two oral GLP-1 options for weight loss. In OASIS 4, oral semaglutide 25 mg taken daily produced an average loss of 13.6% at week 64, versus 2.2% on placebo ^[31][5]. The Wegovy pill’s self-pay price is $149 per month at 1.5 mg, $199 at 4 mg, and $299 at the 9 mg and 25 mg doses ^[3].

Foundayo (orforglipron) was approved by the FDA on April 1, 2026 ^[4]. It is a small-molecule oral GLP-1 receptor agonist that can be taken at any time of day without restrictions on food or water intake ^[4][5]. In the 72-week ATTAIN-1 trial, people on the highest dose who stayed on treatment lost an average of 12.4% of body weight (27.3 lb), versus 0.9% (2.2 lb) on placebo; counting everyone randomized regardless of completion, the averages were 11.1% (25 lb) versus 2.1% ^[4].

Foundayo starts at $149 per month for the lowest self-pay dose; eligible people with commercial insurance may pay $25 per month with the savings card, and eligible Medicare Part D members may get it for $50 per month beginning as soon as July 1, 2026 ^[4][5].

What side effects do GLP-1 drugs have?

Gastrointestinal effects are the most common problem across this class. On the highest Foundayo dose, about one-third of adults reported nausea, roughly one-quarter reported constipation, diarrhea or vomiting, and about 10% stopped the drug because of side effects ^[5]. The Foundayo label warns it may cause thyroid tumors, including thyroid cancer, and that combining it with other GLP-1 drugs is not recommended ^[4]. In OASIS 4, gastrointestinal adverse events were more common with oral semaglutide than with placebo ^[31].

How well does Qsymia work?

Qsymia (phentermine/topiramate extended-release) was approved in July 2012 for adults with a BMI of 30 or higher, or 27 or higher with a weight-related condition such as hypertension, type 2 diabetes or dyslipidemia ^[8].

In EQUIP, adults on the top dose (15 mg/92 mg) lost 10.9% of body weight over 56 weeks, versus 5.1% on the starting dose (3.75 mg/23 mg) and 1.6% on placebo; 67% of the top-dose group lost at least 5% of body weight versus 17% on placebo, and 47% lost at least 10% versus 7% ^[6][7]. In CONQUER, which enrolled 2,487 patients with a BMI of 27 to 45, the 15/92 mg dose produced 9.8% loss and the 7.5/46 mg dose 7.8%, versus 1.2% on placebo; in the SEQUEL extension, the figures were 10.5% and 9.3% ^[7]. In a 56-week study of 223 adolescents ages 12 and older, BMI fell 4.8% on 7.5/46 mg and 7.1% on 15/92 mg, while the placebo group gained 3.3% ^[8].

What does Qsymia cost, and what are its safety rules?

GoodRx lists average cash prices of $249.32 to $275.66 for 30 brand-name capsules, and $165.94 to $251.35 for the generic, depending on dose; GoodRx coupons bring the generic down to $59.05 to $62.80, though some states bar coupons for controlled substances ^[9]. The manufacturer’s cash program charges $74.99 for a 30-day supply, or $210 for a 90-day supply, which works out to $70 per month ^[10].

Qsymia carries a risk of oral clefts in pregnancy. Patients who can become pregnant need a negative pregnancy test before starting, monthly testing, and effective contraception, and the drug is available only through a restricted REMS program ^[8]. Other label warnings include raised heart rate, suicidal ideation, angle-closure glaucoma, cognitive impairment and metabolic acidosis ^[8].

How well does Contrave work, and what does it cost?

Contrave (naltrexone/bupropion ER) was tested in four 56-week COR trials. Intent-to-treat weight loss on the full dose versus placebo: COR-I 5.4% versus 1.3%, COR-II 5.6% versus 1.2%, COR-BMOD 8.1% versus 4.9%, and COR-Diabetes 3.7% versus 1.7% ^[12]. In COR-I, 42% of the drug group lost at least 5% of body weight versus 17% on placebo, and 21% lost at least 10% versus 7% ^[12]. The dosing guidance described in a pharmacy journal review directs stopping the drug if weight loss is under 5% after 12 weeks ^[12].

Contrave carries the antidepressant-class boxed warnings for suicidality inherited from bupropion; nausea was the most common side effect, reported by 32.5% versus 6.7% on placebo ^[12]. A commercial copay card can bring the cost to as little as $20 per month, and a patient assistance program offers a month of medication for $99 or less to uninsured or underinsured patients ^[13].

What about Saxenda and the older five-drug comparison?

A 2016 Journal of the American Medical Association analysis pooled 28 trials with more than 29,000 patients comparing five then-approved drugs — orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate and liraglutide — against placebo ^[11]. After a year, 23% of placebo patients lost at least 5% of body weight, versus 44% to 75% of patients on the drugs ^[11]. Phentermine-topiramate patients were 9 times as likely as placebo patients to reach 5% loss, and liraglutide patients nearly 6 times as likely ^[11]. Liraglutide and naltrexone-bupropion were the most likely to be stopped because of side effects ^[11].

For cost, GoodRx’s 2025 data shows an average out-of-pocket payment of $76 per fill for Saxenda and $34 for generic liraglutide (Saxenda); the Saxenda cash price without coverage is $1,686 per fill ^[19].

What is orlistat, and how much does it cost?

Orlistat works in the gut: Xenical blocks about 30% of dietary fat from being absorbed, and the over-the-counter version Alli blocks about 25%; both are taken three times daily with fat-containing meals ^[17]. In studies, over half of adults taking orlistat lost at least 5% of their body weight after one year ^[13].

Alli 60 mg was approved for over-the-counter sale on February 7, 2007 for adults 18 and older; Xenical and generic orlistat are approved for ages 12 and older ^[16][17]. On June 10, 2026, the FDA approved a label change for Alli warning of a risk of acute kidney injury, advising consumers to ask a health care provider first if they have ever had kidney disease or kidney stones ^[16].

With a GoodRx coupon, 90 Xenical capsules cost $430.37 and 90 generic orlistat capsules $634.16; a 30-count pack of Alli is $36.46, and a 60-count starter pack usually runs under $50 over the counter ^[17].

What about phentermine and other older appetite suppressants?

Phentermine (Adipex-P) was first approved in the United States in 1959. Its label describes it as a short-term adjunct (a few weeks) to exercise, behavior change and calorie restriction, for patients with a BMI of 30 or higher, or 27 or higher with other risk factors ^[18]. It is a Schedule IV controlled substance, tolerance to its appetite-suppressing effect usually develops within a few weeks, and combining it with other weight loss drugs is not recommended ^[18]. Its contraindications include cardiovascular disease, use of MAOIs within 14 days, hyperthyroidism, glaucoma, a history of drug abuse, and pregnancy ^[18].

A 2013 pharmacy journal review listed phentermine resin (Ionamin) and diethylpropion (Tenuate) among the commonly used medications approved for weight loss at that time ^[7]. Phentermine is also sold as Lomaira ^[13]. Cost-wise, the 2025 average out-of-pocket payment was $15 per fill, with lowest listed prices of $12.22 for generic phentermine, $16.35 for Adipex-P and $15.41 for Lomaira ^[19][13].

What is Imcivree for?

Imcivree (setmelanotide) is an injection for rare forms of obesity, not general weight loss. It was approved in November 2020 for obesity caused by POMC, PCSK1 or LEPR deficiency, and later for Bardet-Biedl syndrome ^[20]. In a 66-week trial of 44 BBS patients, average BMI fell 7.9% after 52 weeks of treatment; 61% lost at least 5% of their BMI and 39% lost at least 10% ^[20].

On March 19, 2026, the FDA approved Imcivree for acquired hypothalamic obesity in patients ages 4 and older — the first approved therapy for that condition, which Rhythm estimates affects about 10,000 people in the United States ^[29]. In the 142-patient TRANSCEND trial, BMI fell 15.8% on treatment (n=94) versus a 2.6% increase on placebo (n=48) at 52 weeks, a placebo-adjusted difference of 18.4% ^[29]. Warnings include skin darkening, depression and suicidal ideation, and disturbance of sexual arousal ^[20][29].

Is Plenity a weight loss drug?

Plenity is not a drug. It is an oral hydrogel made from modified cellulose and citric acid that the FDA cleared as a device for adults with a BMI of 25 to 40 ^[21][22]. In the 24-week GLOW study, 59% of adults responded, losing about 10% of body weight (22 lb) or about 3.5 inches from the waist, and Plenity doubled the odds of losing at least 5% of body weight versus placebo; 26% were super-responders who lost about 14% (30 lb) ^[21]. Side effects — diarrhea, bloating, infrequent bowel movements and flatulence — occurred at rates similar to placebo ^[21].

Plenity was sold by prescription subscription at $98 for a four-week supply; its maker, Gelesis, filed for Chapter 7 bankruptcy and ceased operations on October 30, 2023 ^[22][23].

Which weight loss drugs were pulled from the market?

Fenfluramine and dexfenfluramine were withdrawn on September 15, 1997 after being linked to heart valve damage. On July 8, 1997, 24 cases of valve disease in women treated with fenfluramine plus phentermine (“fen-phen”) were publicly reported, with lesions resembling carcinoid valve disease ^[24]. Of 113 spontaneous reports that met the case definition, 98% were in women and 79% involved the fen-phen combination; none involved phentermine alone ^[24]. Twenty-seven patients (24%) needed valve replacement surgery, and three died after surgery ^[24]. Five echocardiogram surveys found valve disease in 30.0% to 38.3% of exposed people, an overall rate of 32.8% ^[24]. Phentermine itself was not withdrawn and remains approved for short-term use ^[24].

Sibutramine (Meridia) produced weight reductions of 3.62 to 5.29 kg ^[7], but on October 7, 2010, the FDA asked Abbott to withdraw it after the SCOUT trial showed a higher risk of heart attack and stroke; the approval withdrawal became effective December 21, 2010 ^[25].

Lorcaserin (Belviq) was approved in 2012 on the condition that its maker run a cardiovascular safety trial of 12,000 patients over 5 years ^[26]. That trial found cancer in 7.7% of lorcaserin patients (462 people) versus 7.1% on placebo (423), with pancreatic, colorectal and lung cancers more frequent in the drug group; on February 13, 2020, the FDA requested withdrawal and Eisai submitted the request ^[26].

How does the 2026 obesity guideline match drugs to health conditions?

On January 13, 2026, the Obesity Association, a division of the American Diabetes Association, published “Pharmacologic Treatment of Obesity in Adults” ^[27][28]. It treats a loss of 5% or more of body weight as beneficial, 10% or more as the target when obesity-related complications are present, and notes that 15% or more may be needed in some cases ^[28][15].

For specific conditions, the guideline lists drugs with demonstrated benefit: tirzepatide and semaglutide for prediabetes; those two plus liraglutide for type 2 diabetes; tirzepatide, semaglutide and orlistat for hypertension; and tirzepatide for sleep apnea ^[15]. It states that non-FDA-approved compounded products are not recommended ^[27]. All approved obesity drugs are contraindicated in pregnancy, and the guideline advises stopping them at least 2 months before a planned pregnancy ^[28].

How do the prices compare side by side?

Most figures below are self-pay prices, coupons or manufacturer offers, which can change at any time; only the Zepbound figure of about $1,086 is a list price ^[2].

Drug	Typical self-pay price or offer
Zepbound (vials)	$299–$449 per month on LillyDirect; list price about $1,086 [2][13]
Wegovy pen	$199 per month for two lowest doses, first 2 fills through December 31, 2026; then $349; HD 7.2 mg $399 [3]
Wegovy pill	$149 (1.5 mg), $199 (4 mg), $299 (9 mg and 25 mg) per month [3]
Foundayo	From $149 per month self-pay; $25 with commercial savings card; $50 Medicare Part D from as soon as July 1, 2026 [4][5]
Qsymia	$74.99 per 30 days in manufacturer cash program; generic coupon $59.05–$62.80 [10][9]
Contrave	As little as $20 per month with commercial copay card; $99 or less via assistance program [13]
Saxenda	$1,686 cash per fill; 2025 average out-of-pocket $76 [19]
Xenical / orlistat	Coupon $430.37–$634.16 per 90 capsules [17]
Alli	60-count usually under $50 over the counter [17]
Phentermine	2025 average $15 per fill; lowest listed $12.22 [19][13]
Plenity (cleared device)	$98 per four-week prescription subscription [22]

Sources

1. Eli Lilly and Company. Zepbound (tirzepatide) showed superior weight loss over Wegovy (semaglutide) in complete SURMOUNT-5 results published in The New England Journal of Medicine. May 11, 2025.
2. CNBC. Eli Lilly cuts cash prices of Zepbound weight loss drug vials on direct-to-consumer site. December 1, 2025.
3. NovoCare Pharmacy. Get your GLP-1 medications delivered with NovoCare Pharmacy.
4. Eli Lilly and Company. FDA approves Lilly’s Foundayo (orforglipron), the only GLP-1 pill for weight loss that can be taken any time of day without food or water restrictions. April 1, 2026.
5. Everyday Health. FDA approves new type of GLP-1 pill for weight loss. April 1, 2026.
6. Qsymia HCP Website. Study: EQUIP clinical trial.
7. PubMed Central. Phentermine/Topiramate Extended-Release Capsules (Qsymia) for Weight Loss.
8. US Food and Drug Administration. FDA approves treatment for chronic weight management in pediatric patients aged 12 years and older.
9. GoodRx. Qsymia cost guide: prices and savings tips. February 20, 2025.
10. Qsymia. Multiple ways to save on Qsymia.
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13. GoodRx. Phentermine alternatives: 6 weight-loss medications to consider.
14. PubMed. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. January 2004.
15. Medscape. Standards of Care in Overweight and Obesity: Pharmacologic Treatment. April 27, 2026.
16. Drugs.com. Alli (orlistat) FDA approval history. July 8, 2026.
17. GoodRx. How much does Xenical (orlistat) cost?
18. US Food and Drug Administration. Adipex-P (phentermine hydrochloride) capsules label. 2012.
19. GoodRx. Fills for weight-loss medications increase despite high costs.
20. US Food and Drug Administration. FDA approves treatment for weight management in patients with Bardet-Biedl Syndrome aged 6 or older.
21. Gelesis. Plenity: non-systemic aid to weight management.
22. Forbes Health. Plenity review. January 10, 2024.
23. US Securities and Exchange Commission. Gelesis Holdings, Inc. Form 8-K. October 30, 2023.
24. Centers for Disease Control and Prevention. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: interim public health recommendations. November 1997.
25. Federal Register. Abbott Laboratories, Inc.; Withdrawal of approval of a new drug application for MERIDIA. December 21, 2010.
26. US Food and Drug Administration. FDA requests the withdrawal of the weight-loss drug Belviq, Belviq XR (lorcaserin) from the market.
27. American Diabetes Association. The Obesity Association publishes new Standards of Care section on obesity medications. January 13, 2026.
28. HCPLive. ADA’s Obesity Association releases guidelines for use of obesity medications. January 13, 2026.
29. Rhythm Pharmaceuticals. Rhythm Pharmaceuticals announces FDA approval of IMCIVREE (setmelanotide) for patients with acquired hypothalamic obesity. March 19, 2026.
30. PubMed. Once-weekly semaglutide in adults with overweight or obesity.
31. New England Journal of Medicine. Oral semaglutide at a dose of 25 mg in adults with overweight or obesity.
32. PubMed. Valvular heart disease associated with fenfluramine-phentermine. The New England Journal of Medicine. August 28, 1997.