Every FDA-Approved Weight Loss Drug, Compared (2026)

There are more FDA-approved weight-management options in 2026 than at any point in American history, and more of them work than at any point in American history. This is the complete list, ranked by how much weight they produce in trials, with what each one costs and who it suits.

One note before the table: these trials differ in length, population and statistical method. A 20.2% result from a 72-week trial and a 5.4% result from a 56-week trial are not perfectly comparable. Treat this as a ladder, not a leaderboard.

The full comparison table

Drug (brand)	Form	Trial	Mean weight loss	Self-pay cost/month (2026)
Tirzepatide (Zepbound)	Weekly injection	SURMOUNT-5, 72 wk	20.2%	$299–$449
Semaglutide (Wegovy)	Weekly injection	STEP 1, 68 wk	14.9%	$349 ($399 HD; $199 intro)
Semaglutide (Wegovy pill)	Daily tablet	OASIS 4, 64 wk	~17% on treatment; ~14% regardless	$149–$299 by dose
Orforglipron (Foundayo)	Daily tablet	ATTAIN-1, 72 wk	12.4% (top dose)	From $149
Phentermine/topiramate ER (Qsymia)	Daily capsule	EQUIP, 56 wk	10.9%	$59–$75 generic/cash program
Liraglutide (Saxenda)	Daily injection	SCALE, 56 wk	~8%	Varies; generic available
Plenity (device)	Capsules before meals	GLOW, 24 wk	6.4%	Historically $98
Naltrexone/bupropion ER (Contrave)	Twice-daily tablets	COR-I, 56 wk	5.4% (ITT)	$20–$99 with programs
Orlistat (Xenical)	Three times daily	XENDOS, 1 yr / 4 yr	10.6 kg / 5.8 kg	$430–$634 per 90 capsules
Phentermine (Adipex-P)	Daily capsule/tablet	Short-term trials	~3–5% (12 wk)	$14–$41
Orlistat 60 mg (Alli, OTC)	Three times daily	OTC-dose trials	Small	~$36–$90
Setmelanotide (Imcivree)	Daily injection	Genetic obesity trials	Condition-specific	Specialty

Sources for each figure appear in the sections below.

The incretin drugs: tirzepatide, semaglutide and orforglipron

These are the modern class and the reason the field looks different than it did in 2020.

Tirzepatide (Zepbound) is a dual GIP and GLP-1 receptor agonist given as a weekly injection, approved in 2023. In SURMOUNT-5, the open-label head-to-head trial of 751 participants published in the New England Journal of Medicine, tirzepatide produced 20.2% mean weight loss at 72 weeks versus 13.7% for semaglutide, equal to 22.8 kg versus 15.0 kg [1]. It also outperformed on every threshold: 81.6% versus 60.5% reached 10% loss, and 48.4% versus 27.3% reached 20% [1]. Waist circumference fell 18.4 cm versus 13.0 cm [1].

Self-pay pricing through LillyDirect is $299 per month for the 2.5 mg starting dose, $399 for 5 mg and $449 for higher doses [2]. The $449 tier is conditional on refilling within 45 days; Lilly’s stated regular self-pay prices otherwise are $499 for 7.5 mg and $699 for 10, 12.5 and 15 mg, so a lapsed refill can raise the real monthly cost well above the headline number.

Semaglutide (Wegovy) is a weekly GLP-1 receptor agonist approved in 2021. STEP 1, a 68-week trial in 1,961 adults published in the New England Journal of Medicine, produced a mean weight change of −14.9% against −2.4% on placebo, an estimated treatment difference of 12.4 percentage points (95% CI −13.4 to −11.5, P<0.001); 86.4% of the semaglutide group lost at least 5% and 50.5% lost at least 15% [30]. NovoCare self-pay is $349 per month for standard doses and $399 for Wegovy HD 7.2 mg, with a $199 introductory price on the two starter doses for the first two fills through December 31, 2026 [3].

Semaglutide tablets (the Wegovy pill) were approved on December 22, 2025 — the first oral GLP-1 for chronic weight management — and launched in early January 2026. In OASIS 4, published in the New England Journal of Medicine, oral semaglutide 25 mg produced roughly 17% mean weight loss at 64 weeks among participants who stayed on treatment, and about 14% regardless of discontinuation [31]. Self-pay is $149 per month for the 1.5 mg starter dose, $199 for 4 mg and $299 for the 9 mg and 25 mg doses.

Orforglipron (Foundayo) is the newest entry and a genuine landmark: a small-molecule oral GLP-1 that can be taken at any time of day without food or water restrictions. The FDA approved it on April 1, 2026, under the national priority voucher program [4]. In ATTAIN-1 (n=3,127), people on the highest 36 mg dose who stayed on treatment lost an average of 27.3 pounds, or 12.4% of body weight, at 72 weeks, versus 2.2 pounds or 0.9% on placebo [4]. Including everyone regardless of completion, it was 25 pounds (11.1%) versus 5.3 pounds (2.1%) [4]. Self-pay starts at $149 per month, and eligible Medicare members may access $50 monthly from July 1, 2026 [5].

Shared risks across the class: gastrointestinal side effects dominate (nausea, vomiting, diarrhea, constipation), with less common but serious concerns including pancreatitis and gallbladder disease, and a boxed warning for thyroid C-cell tumors based on rodent data. See this site’s safety lane for the complete picture.

Phentermine/topiramate ER (Qsymia): the best non-incretin pill

Approved in 2012, and until 2026 the most effective weight-loss pill available.

In EQUIP (n=1,267, 56 weeks, BMI 35 or greater), the 15/92 mg dose produced 10.9% weight loss versus 1.6% on placebo, with 67% of patients losing at least 5% and 47% losing at least 10%, against 17% and 7% on placebo [6]. CONQUER (n=2,487) produced 9.8% on the same dose and 7.8% on 7.5/46 mg [7]. The SEQUEL two-year extension found the effect held at 10.5% [7].

A pediatric indication for patients 12 and older was approved in 2022; in the 223-participant trial, BMI fell 4.8% on 7.5/46 mg and 7.1% on 15/92 mg, while the placebo group gained 3.3% of BMI [8].

A generic launched in the US on May 7, 2025 after FDA approval in June 2024, and runs roughly $59 to $63 per month with a coupon against $249 to $276 average retail for the brand [9]. The manufacturer’s cash program is $74.99 per month or $70 on a 90-day supply [10].

Key risks: topiramate is associated with oral clefts in the first trimester, so the label requires a negative pregnancy test before starting and monthly thereafter in people who can become pregnant, plus effective contraception. Paresthesia, dry mouth, constipation, taste changes, insomnia, cognitive slowing, kidney stones, metabolic acidosis and acute angle-closure glaucoma are all on the label. Schedule IV.

Liraglutide (Saxenda): the first-generation GLP-1

A daily injectable GLP-1 approved in 2014, producing roughly 8% mean weight loss at 56 weeks in the SCALE program. Generic liraglutide has entered the US market, which has made it the cheapest branded-molecule incretin option. It has been superseded on efficacy by the weekly drugs but remains relevant on price and for people who tolerate daily dosing better.

In the 2016 Khera network meta-analysis of 29,018 participants, 63% of liraglutide recipients reached 5% weight loss versus 23% on placebo, putting it second only to phentermine-topiramate among the drugs available then [11].

Naltrexone/bupropion ER (Contrave): the craving drug

Approved September 2014. In the intent-to-treat analyses of the four COR trials, weight loss ranged from 3.7% (COR-Diabetes) to 8.1% (COR-BMOD, which added intensive behavior modification), with COR-I at 5.4% versus 1.3% on placebo [12]. Pooled placebo-subtracted mean weight loss at one year was 4.7%.

Discontinuation was high: in COR-I, 49.2% of the Contrave group and 50.1% of the placebo group stopped study drug before week 56 [12].

With a commercial copay card it can cost as little as $20 per month, and the patient assistance program offers a month for $99 or less for the uninsured or underinsured [13].

Key risks: a boxed warning for suicidal thoughts and behaviors, inherited from bupropion. Contraindicated in seizure disorder, bulimia or anorexia nervosa, chronic opioid use, uncontrolled hypertension, MAOI use and abrupt alcohol or benzodiazepine discontinuation.

Orlistat (Xenical and Alli): the gut drug

The only approved weight drug that never reaches your brain, and the one with the longest randomized trial.

XENDOS randomized 3,305 people with obesity to orlistat 120 mg three times daily or placebo, both with lifestyle counseling, for four years. Mean weight loss was 10.6 kg versus 6.2 kg at one year, narrowing to 5.8 kg versus 3.0 kg at four years (P<0.001) [14]. Progression to type 2 diabetes fell from 9.0% to 6.2%, a hazard ratio of 0.63 [14].

That diabetes-prevention finding is orlistat’s real asset, and it is why the 2026 standards list orlistat as having demonstrated benefit for hypertension and potential benefit for prediabetes and type 2 diabetes [15].

The problem is tolerability. In XENDOS, 91% of the orlistat arm reported gastrointestinal side effects in year one, versus 65% on placebo; by year four it was 36% versus 23% [14]. Those effects are worse the more fat you eat, which enforces a low-fat diet whether you wanted one or not.

Alli is orlistat 60 mg, approved over the counter on February 7, 2007 for adults 18 and older with a BMI of 25 or higher [16]. It is the only non-prescription weight-loss drug the FDA has ever approved. A 30-count starter pack runs about $36 and a 60-count pack is usually under $50 [17].

Prescription orlistat is oddly expensive for an old drug: brand Xenical runs about $430 per 90 capsules with a coupon, and the authorized generic is often more at about $634 [17].

Phentermine alone: cheap, fast and short-term by label

Approved in 1959, Schedule IV, and still among the three most prescribed obesity medications in the United States. It produces roughly 3% to 5% of body weight over about 12 weeks.

The critical thing to understand is the label: Adipex-P is indicated “only as short-term (a few weeks) monotherapy for the management of exogenous obesity” [18]. It also explicitly states that co-administration with other weight-loss drugs is not recommended [18].

It costs about $37 to $41 for 30 tablets at average retail, or as low as roughly $14 with a coupon where state law permits coupons on controlled substances. GoodRx claims data put average out-of-pocket spend at about $15 per fill in 2025 [19].

Setmelanotide (Imcivree): the rare-disease drug

A daily injectable MC4R agonist approved in 2020 for obesity due to POMC, PCSK1 or LEPR deficiency, expanded in 2022 to Bardet-Biedl syndrome and, on March 19, 2026, to acquired hypothalamic obesity in adults and children aged 4 and older — the first approved therapy for that condition [20][29].

It belongs on the list because it is an FDA-approved obesity drug, but it is not a general-population option. Eligibility requires genetic confirmation or a specific clinical history.

Results in its target populations are substantial: 80% of patients with POMC or PCSK1 deficiency and 45.5% with LEPR deficiency lost 10% or more of body weight at one year. In Bardet-Biedl syndrome, mean BMI fell 7.9% at 52 weeks [20]. In the phase 3 TRANSCEND trial in acquired hypothalamic obesity (n=142, randomized 2:1), mean BMI fell 15.8% on setmelanotide (n=94) against a 2.6% increase on placebo (n=48) at 52 weeks, a placebo-adjusted reduction of 18.4% (P<0.0001) [29].

Plenity: FDA-cleared, but not a drug

Plenity is a superabsorbent hydrogel made from cellulose and citric acid, cleared by the FDA in 2019 as a medical device, not approved as a drug. It expands in the stomach, occupying volume, then passes through.

In the GLOW study (n=436, 24 weeks), mean weight loss was 6.4% versus 4.4% on placebo. Fifty-nine percent of treated adults were responders, losing an average of about 10% of body weight or about 3.5 inches from the waist, and Plenity doubled the odds of achieving 5% or greater weight loss compared with placebo. Forty-four percent lost 10% or more, versus 14% on placebo [21]. An extension found 7.6% at 48 weeks among continuers.

It has historically cost $98 for a four-week supply through a telehealth subscription [22]. A caution: Gelesis Holdings filed for Chapter 7 liquidation on October 30, 2023 and ceased operations, with assets sold through the bankruptcy trustee in 2024 [23]. Verify current US availability before assuming you can get it.

The withdrawn drugs, and why they matter

Three drugs have been removed from the US market, and each one shaped the rules that followed.

Fenfluramine and dexfenfluramine (1997). On July 8, 1997, Mayo Clinic researchers publicly reported 24 cases of valvular heart disease in women treated with fenfluramine and phentermine; the full report appeared in the New England Journal of Medicine on August 28, 1997 [32]. The lesions resembled carcinoid-induced valvular disease, a serotonin-related pattern. On September 15, 1997, the manufacturers and the FDA announced withdrawal [24]. Five echocardiographic prevalence surveys reported to the FDA that year found valvular disease meeting the case definition in 30.0% to 38.3% of exposed people, overall 32.8% (95% CI 27.7%–38.9%) — but those surveys had no unexposed controls, and later controlled work found complication rates under 3% for exposures of three months or less [24]. The often-quoted “$13 billion” is a 2003 Forbes figure for what Wyeth had paid in Pondimin and Redux claims; the court-approved national class settlement was $4.75 billion in 2000, later valued near $7.65 billion. Phentermine itself was not withdrawn.

Sibutramine (Meridia, 2010). The SCOUT cardiovascular outcomes trial found a 16% increase in serious cardiovascular events. The FDA requested withdrawal on October 8, 2010; approval was formally withdrawn effective December 21, 2010 [25]. Sibutramine remains the most common undeclared adulterant found in illegal weight-loss supplements.

Lorcaserin (Belviq, 2020). The CAMELLIA-TIMI 61 trial, an FDA-required cardiovascular safety study of about 12,000 patients over five years, found cancer in 7.7% of lorcaserin recipients versus 7.1% on placebo, with pancreatic, colorectal and lung cancers more frequent in the lorcaserin arm. The FDA requested withdrawal on February 13, 2020; Eisai complied while stating its interpretation of the data differed [26]. Approval was withdrawn effective September 17, 2020.

The lesson consumers should take is not that weight-loss drugs are inherently unsafe. It is that these three were caught by post-approval outcome trials that the FDA now requires, and that the current incretin class has been through, and continues to be monitored by, exactly those systems.

How do you choose?

The Obesity Association, a division of the American Diabetes Association, published “Pharmacologic Treatment of Obesity in Adults” on January 13, 2026, in the inaugural edition of Diabetes, Obesity, and Cardiometabolic CARE [27].

Its Grade A recommendations include offering obesity medications as part of initial treatment for adults with or at high risk of obesity-related diseases or complications [27]. Its framework is explicitly about matching magnitude to need:

Weight reduction needed	Options the guidance points to
10% or more	Tirzepatide, semaglutide
5% to 10%	Phentermine-topiramate
Less than that	Naltrexone-bupropion, liraglutide, phentermine alone, orlistat

By coexisting condition [15]:

Condition	Demonstrated benefit	Potential benefit
Prediabetes	Tirzepatide, semaglutide	Phentermine-topiramate, liraglutide, orlistat
Type 2 diabetes	Tirzepatide, semaglutide, liraglutide	Phentermine-topiramate, naltrexone-bupropion, orlistat
Hypertension	Tirzepatide, semaglutide, orlistat	Phentermine-topiramate, liraglutide

The guidance also emphasizes that a 5% or greater weight reduction is beneficial, 10% or more is recommended when obesity-related complications are present, and 15% or more may be needed in some cases [28].

What this list does not include

Everything sold without a prescription other than Alli. Berberine, GLP-1 boosters, GLP-1 patches, apple cider vinegar gummies, garcinia cambogia and every other supplement in the category have not been through FDA pre-market review for safety or effectiveness. The Obesity Society’s systematic review of 315 randomized trials of supplements and alternative therapies found only 16 that showed a significant weight difference versus placebo, with effects ranging from 0.3 to 4.93 kg.

It also does not include compounded semaglutide or tirzepatide, or gray-market “research peptides.” Those are covered in this site’s compounding and safety lanes.

The short version

The most effective approved weight-loss drug in America right now is tirzepatide, at 20.2%. The most effective pill is the Wegovy pill at roughly 17% on treatment, with orforglipron at 12.4%. The cheapest drug with double-digit efficacy is generic phentermine/topiramate ER at roughly $60 a month. The cheapest drug of any kind is phentermine at roughly $15 a fill, labeled for a few weeks. The only over-the-counter option is Alli.

Which one is right depends on how much weight reduction your health actually requires, what else is going on medically, what your insurance covers, and which side-effect profile you can live with for the long run. That is a conversation for a prescriber, and the 2026 standards give you a good framework to open it with.

This article summarizes what FDA-approved labeling and Instructions for Use, published trials and professional guidelines report. It is not medical advice and does not recommend a drug or a dose. Follow your own prescription and the directions your prescriber and pharmacist give you. Prices change frequently; verify before deciding.

Sources

1. Eli Lilly — SURMOUNT-5 complete results published in NEJM: https://investor.lilly.com/news-releases/news-release-details/zepbound-tirzepatide-showed-superior-weight-loss-over-wegovy
2. CNBC — Eli Lilly cuts cash prices of Zepbound vials: https://www.cnbc.com/2025/12/01/eli-lilly-prices-zepbound-weight-loss-drug-vials.html
3. NovoCare Pharmacy: https://www.novocare.com/pharmacy.html
4. Eli Lilly — FDA approves Foundayo (orforglipron): https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-foundayotm-orforglipron-only-glp-1-pill
5. Everyday Health — New GLP-1 pill Foundayo gets FDA approval for obesity: https://www.everydayhealth.com/obesity/fda-approves-new-type-of-glp-1-pill-for-weight-loss
6. Qsymia HCP — EQUIP adult clinical trial: https://hcp.qsymia.com/efficacy-and-safety/study-equip
7. Phentermine/topiramate ER for weight loss — EQUIP, CONQUER and SEQUEL results: https://pmc.ncbi.nlm.nih.gov/articles/PMC3814438
8. FDA — Approval for chronic weight management in pediatric patients aged 12 and older: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-chronic-weight-management-pediatric-patients-aged-12-years-and-older
9. GoodRx — Qsymia cost guide: https://www.goodrx.com/qsymia/qsymia-cost
10. Qsymia — multiple ways to save: https://qsymia.com/patient/multiple-ways-to-save
11. CardioSmart / ACC — Khera 2016 network meta-analysis summary: https://www.cardiosmart.org/news/2016/7/study-confirms-the-benefits-of-fda-approved-weight-loss-pills
12. Naltrexone/bupropion ER (Contrave) — COR trial results: https://pmc.ncbi.nlm.nih.gov/articles/PMC4771085
13. GoodRx — Phentermine alternatives: 6 weight-loss medications to consider: https://www.goodrx.com/conditions/weight-loss/phentermine-alternatives
14. Torgerson JS et al., Diabetes Care 2004 — XENDOS: https://pubmed.ncbi.nlm.nih.gov/14693982
15. Obesity Association / ADA — Standards of Care in Overweight and Obesity: pharmacologic treatment, 2026: https://reference.medscape.com/cc2/p10/standards-care-overweight-obesity-ada-guidelines-2026a1000cjs
16. Drugs.com — Alli FDA approval history: https://www.drugs.com/history/alli.html
17. GoodRx — How much does Xenical (orlistat) cost?: https://www.goodrx.com/xenical/xenical-cost-without-insurance
18. FDA label, Adipex-P (phentermine hydrochloride): https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/085128s065lbl.pdf
19. GoodRx Research — Weight-loss medication fill tracker: https://www.goodrx.com/healthcare-access/research/weight-loss-medication-fill-tracker
20. FDA — Imcivree approval for Bardet-Biedl syndrome: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-weight-management-patients-bardet-biedl-syndrome-aged-6-or-older
21. Gelesis — Plenity clinical data (GLOW): https://www.gelesis.com/en/products/plenity-weight-management
22. Forbes Health — Plenity review: https://www.forbes.com/health/weight-loss/plenity-weight-loss-review
23. SEC Form 8-K — Gelesis Holdings Chapter 7 filing, October 30, 2023: https://www.sec.gov/Archives/edgar/data/1805087/000095017023056517/gls-20231030.htm
24. CDC MMWR — Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: https://www.cdc.gov/mmwr/preview/mmwrhtml/00049815.htm
25. Federal Register — Withdrawal of approval of NDA for Meridia: https://www.federalregister.gov/documents/2010/12/21/2010-31986/abbott-laboratories-inc-withdrawal-of-approval-of-a-new-drug-application-for-meridia
26. FDA — FDA requests the withdrawal of the weight-loss drug Belviq: https://www.fda.gov/drugs/drug-safety-communications/fda-requests-withdrawal-weight-loss-drug-belviq-belviq-xr-lorcaserin-market
27. American Diabetes Association — The Obesity Association publishes new Standards of Care section on obesity medications: https://diabetes.org/newsroom/press-releases/obesity-association-publishes-new-standards-care-section-obesity
28. HCPLive — ADA’s Obesity Association releases guidelines for use of obesity medications: https://www.hcplive.com/view/ada-s-obesity-association-releases-guidelines-for-use-of-obesity-medications
29. Rhythm Pharmaceuticals — FDA approval of Imcivree (setmelanotide) for acquired hypothalamic obesity, March 19, 2026, with phase 3 TRANSCEND results (NCT05774756): https://ir.rhythmtx.com/news-releases/news-release-details/rhythm-pharmaceuticals-announces-fda-approval-imcivreer-1
30. Wilding JPH et al., N Engl J Med 2021;384(11):989-1002 — Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1, NCT03548935): https://pubmed.ncbi.nlm.nih.gov/33567185
31. Wharton S, Lingvay I, Bogdanski P, et al. — Oral semaglutide 25 mg in adults with overweight or obesity, N Engl J Med 2025;393:1077-1087 (OASIS 4), doi 10.1056/NEJMoa2500969: https://www.nejm.org/doi/10.1056/NEJMoa2500969
32. Connolly HM, Crary JL, McGoon MD, et al. — Valvular heart disease associated with fenfluramine-phentermine, N Engl J Med 1997;337(9):581-588: https://pubmed.ncbi.nlm.nih.gov/9271479