The New Weight-Loss Drugs, Compared (2026)

TL;DR: The weight-loss drug field has moved fast. Three are FDA-approved today: semaglutide (Ozempic, Wegovy), which lowers weight by about 15% and has proof it cuts heart attacks and strokes; tirzepatide (Mounjaro, Zepbound), the most powerful approved option at about 20%; and orforglipron (Foundayo), the first oral pill, at about 11 to 12%. Two more are close behind but not yet approved: retatrutide, a triple-hormone drug that reached roughly 24% in early trials and about 28 to 30% in its phase 3 program, and CagriSema, an amylin-plus-GLP-1 combination at about 22.7% that lost its head-to-head against tirzepatide. The strongest approved drug is tirzepatide; the most convenient is the orforglipron pill; the one with proven heart benefit is semaglutide. Most of these numbers come from separate trials, so cross-drug rankings are estimates, and the best drug is the one you can stay on while protecting your muscle.

The landscape at a glance

Here is how the current and emerging weight-loss drugs line up. The weight-loss figures are averages from each drug's own trials at the top dose, so treat cross-drug comparisons as approximate rather than head-to-head unless noted.

The drugs you can get today

Three of these are approved and prescribable now.

Semaglutide, sold as Ozempic for diabetes and Wegovy for weight, is the drug that started the wave. It quiets appetite through the GLP-1 pathway and lowers weight by about 15%.¹ Its distinction is proof beyond weight: in a large trial it lowered heart attacks and strokes in people with heart disease and obesity, which none of the newer drugs has yet matched.² It also comes as a daily pill, Rybelsus, though that version needs careful timing on an empty stomach.

Tirzepatide, sold as Mounjaro and Zepbound, is the most powerful approved option, at about 20% weight loss.³ It adds a second hormone, GIP, to semaglutide's GLP-1, and in the one trial that compared the two directly, it produced clearly more weight loss. It also helps a hard-to-treat form of heart failure and is the first drug approved for obstructive sleep apnea in obesity.

Orforglipron, sold as Foundayo, is the newest and the most convenient: the first true oral pill in this class, approved for weight in 2026, taken once a day with no food or water rules. Its weight loss, about 11 to 12%, is more modest than the injections, so its appeal is ease and access rather than raw power.⁴

The drugs on the horizon

Five more are worth understanding, with the caution that none is approved in the United States, though one, mazdutide, is already approved in China.

Retatrutide is the one to watch on sheer weight loss. It adds a third hormone, glucagon, to the GIP and GLP-1 of tirzepatide, and that extra push on energy burning drove roughly 24% weight loss in early trials and about 28 to 30% in its phase 3 program, the most reported for any obesity drug.⁵ The trade-offs are that it is investigational, its glucagon action raises heart rate, and it has no heart-outcome data yet.

CagriSema takes a different route, pairing semaglutide with cagrilintide, a long-acting version of the satiety hormone amylin. It reached about 22.7% in its main trial, a strong result, but it came in below expectations and, in a head-to-head, did not prove as good as tirzepatide.⁶ Its interest lies in its amylin mechanism rather than in beating what is already available.

Survodutide takes the glucagon route like retatrutide, but pairs it with GLP-1 alone, without GIP, and leans it toward the liver. It produced about 16.6% weight loss in its phase 3 obesity trial, below the highest numbers here, but its standout result is in MASH, the scarring form of fatty liver disease, where it improved the disease on biopsy in a majority of people and earned a breakthrough therapy designation.⁸ It, too, is investigational, and its glucagon action raises heart rate.

Amycretin, recently named zenagamtide, is the earliest of these and the most novel in form. Like CagriSema it pairs amylin with GLP-1, but it does so in a single molecule, and it is being built as both an injection and a daily pill. In small early trials the injection produced about 22 to 24% weight loss over 36 weeks and the pill about 13% over 12 weeks, though these are phase 1 and phase 2 numbers, well short of the large trials that settle a drug's effect.⁹ Its phase 3 program began in 2026.

Mazdutide is the outlier, because it is already approved, though only in China and not the United States. It is a GLP-1/glucagon dual agonist like survodutide, based on the natural gut hormone oxyntomodulin, and in its main trial Chinese adults lost about 11 to 14% of their weight at the approved doses over 48 weeks, with a higher dose reaching about 20% in a separate study.¹⁰ It also lowered blood pressure, lipids, and uric acid. Eli Lilly holds the rights outside China, but there is no US approval.

How they compare head to head

Most weight-loss drug comparisons you will see are cross-trial: each number comes from a different study with a different population, so lining them up gives a rough picture rather than a fair contest. Only two proper head-to-head trials exist so far, and both involve tirzepatide.

In the first, tirzepatide was tested directly against semaglutide at their full obesity doses, and tirzepatide won, about 20% versus 14%.⁷ In the second, tirzepatide was tested against CagriSema, and again tirzepatide came out ahead, with CagriSema failing to prove it was even equal. So among the drugs that have been compared directly, tirzepatide is the one to beat. Retatrutide's phase 3 numbers look higher still, but it has not been tested against tirzepatide head-to-head, so that ranking remains an estimate.

The rough summary of the potency order, keeping the cross-trial caveat in mind, runs roughly: orforglipron (the pill) lowest, then semaglutide, then tirzepatide, with the investigational CagriSema near tirzepatide and retatrutide likely highest of all. But potency is only one axis, and rarely the only thing that decides.

Which weight-loss drug is right for you?

The best drug is rarely the strongest one on paper; it is the one that fits your body, your goals, and your life well enough that you stay on it. A few axes matter more than the raw weight-loss number.

If you want the most weight loss from an approved drug, tirzepatide leads. If you value a pill over an injection, orforglipron is the option, accepting somewhat less weight loss for the convenience. If you have established heart disease and want a drug proven to lower cardiovascular events, semaglutide has that evidence today. If cost or supply is the barrier, the answer is often whichever effective drug you can get and afford. And across all of them, the same rule holds: pair the drug with enough protein and resistance training to protect muscle, since a large share of any rapid weight loss is muscle, and set up a plan for the long term, since stopping tends to bring weight back. Our muscle-first weight-loss approach covers that side in depth.

The two investigational drugs, retatrutide and CagriSema, are worth following but not worth waiting for. Starting now with an approved drug and reassessing when the newer ones arrive is almost always wiser than delaying care for a medicine that may or may not offer you an edge.

Guidance from the Clinic

"Patients come in having read about one of these drugs and wanting it by name, and my job is to widen the lens. The right question is not which drug is strongest in a headline; it is which one fits you. For someone who needs the biggest drop and will take an injection, tirzepatide is my usual answer today. For someone who dreads needles, the orforglipron pill changed what I can offer. For someone with heart disease, semaglutide's outcome data carries weight. I am excited about retatrutide and watching CagriSema, but I do not put patients in a holding pattern for drugs that are not approved. Whatever we choose, I build the plan around protecting muscle and building habits, because the drug is the accelerant, and the life around it is what makes the result last."

Related at Fishtown Medicine

• Tirzepatide (Zepbound, Mounjaro) - the strongest approved drug in depth
• Orforglipron (Foundayo) - the oral pill in depth
• Retatrutide: The Triple Agonist - the highest emerging weight loss
• CagriSema (Cagrilintide + Semaglutide) - the amylin combination
• Survodutide (GLP-1/Glucagon) - the glucagon dual agonist built for the liver
• Amycretin (Amylin/GLP-1) - the single-molecule amylin drug, in a pill and a shot
• Mazdutide (GLP-1/Glucagon) - the oxyntomodulin drug approved in China
• Ozempic vs Metformin - semaglutide and the foundation drugs
• Muscle Loss on GLP-1 Drugs - protecting lean mass on any of these

Scientific References

1. Wilding JPH, Batterham RL, Calanna S, et al. "Once-Weekly Semaglutide in Adults with Overweight or Obesity." New England Journal of Medicine. 2021;384(11):989-1002.
2. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. "Semaglutide and Cardiovascular Outcomes in Obesity Without Diabetes." New England Journal of Medicine. 2023;389(24):2221-2232.
3. Jastreboff AM, Aronne LJ, Ahmad NN, et al. "Tirzepatide Once Weekly for the Treatment of Obesity." New England Journal of Medicine. 2022;387(3):205-216.
4. Wharton S, et al. "Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment." New England Journal of Medicine. 2025;393:1796-1806.
5. Jastreboff AM, et al. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial." New England Journal of Medicine. 2023;389(6):514-526.
6. Garvey WT, et al. "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity." New England Journal of Medicine. 2025;393(7):635-647.
7. Aronne LJ, Horn DB, le Roux CW, et al. "Tirzepatide as Compared with Semaglutide for the Treatment of Obesity." New England Journal of Medicine. 2025.
8. Sanyal AJ, Bedossa P, Fraessdorf M, et al. "A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis." New England Journal of Medicine. 2024;391(4):311-319.
9. Dahl K, Toubro S, Dey S, et al. "Amycretin, a Novel, Unimolecular GLP-1 and Amylin Receptor Agonist Administered Subcutaneously: Results from a Phase 1b/2a Randomised Controlled Study." The Lancet. 2025. DOI: 10.1016/S0140-6736(25)01185-7.
10. Ji L, Jiang H, Bi Y, et al. "Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight." New England Journal of Medicine. 2025;392(22):2215-2225.