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Demand for effective obesity medication continues to grow as more people struggle to achieve a healthy body weight. Several next-generation treatments are expected to reach the market or advance into pivotal trials in 2026.

These therapies go beyond first-generation glucagon-like-peptide-1 (GLP-1) agonists by combining multiple metabolic pathways, offering oral dosing or longer dosing intervals, and aiming for greater weight reductions with fewer side effects.

This article reviews nine promising candidates, explaining how they work, summarizing trial results, and anticipating when they might become available.

Key Takeaways

  • Weight loss efficacy from new weight loss drugs is increasing, with retatrutide reaching nearly 29% average weight loss and several dual agents delivering 15% to 23% reductions in Phase 2 and 3 trials.
  • Multiple mechanisms are being combined, including GLP-1, GIP, glucagon, and amylin pathways, to enhance satiety, energy expenditure, and metabolic control.
  • More dosing options are coming, including once-monthly injectables like MariTide and PF-08653944 and oral agents such as orforglipron and VK2735 tablets.
  • Metabolic benefits extend beyond weight, with many candidates improving A1c, blood pressure, liver fat, and lipid levels.
  • Safety profiles remain consistent with the incretin class, with mostly mild to moderate gastrointestinal effects during dose escalation in clinical trials.

1. Retatrutide

Retatrutide, nicknamed “Triple G” in the media and scientific commentary, is Eli Lilly’s triple receptor agonist that activates GIP, GLP-1, and glucagon receptors. Retatrutide aims to maximize satiety, increase energy expenditure, and improve glucose control by stimulating three complementary pathways.

In the phase 3 TRIUMPH 4 trial, participants with obesity and knee osteoarthritis treated with 12 mg retatrutide lost 28.7% of their body weight (about 71.2 lbs) at 68 weeks. Weight loss appeared dose-dependent, and additional phase 3 trials are ongoing with expected completion in 2026.

Gastrointestinal symptoms such as nausea and diarrhea were common but generally mild. The trial also reported improvements in knee pain (by up to 75.8%) and physical function, suggesting benefits beyond weight loss. If results hold across the broader program, retatrutide could become the most effective pharmaceutical for obesity yet.

2. CagriSema

CagriSema pairs cagrilintide, an amylin analogue, with semaglutide, the active ingredient in Wegovy, Ozempic, and Rybelsus. Amylin-like drugs help you feel full and reduce glucagon levels, which is a hormone made by your pancreas that raises blood sugar.

In the phase 3 REDEFINE 1 trial, once-weekly CagriSema produced an average weight loss of 20.4% at week 68, rising to 22.7% with full treatment adherence. In participants with type 2 diabetes (REDEFINE 2), weight loss averaged 13.7%, increasing to 15.7% with full adherence.

However, in its most recent study, REDEFINE 4, CagriSema did not outperform tirzepatide in weight loss. After 84 weeks, people taking CagriSema 2.4 mg/2.4 mg lost an average of 23% of their body weight, compared to 25.5% in those taking tirzepatide 15 mg.

CagriSema was submitted to the US FDA in December 2025 for weight management after results from REDEFINE 1 and REDEFINE 2. A decision from the FDA is expected by late 2026. A separate phase 3 trial testing an even higher dose is planned to begin in the second half of 2026.

3. MariTide (maridebart cafraglutide or AMG 133)

Maridebart cafraglutide, marketed as MariTide, is Amgen’s once-monthly or less frequent injectable that combines an amylin analogue with a GLP-1 agonist. It is designed as a long-acting antibody-peptide medicine, which could help maintain weight loss and possibly reduce weight regain after stopping treatment.

In its phase 2 study, adults without type 2 diabetes experienced up to 20% average weight loss at 52 weeks, while participants with diabetes lost 17%. The trial noted that weight loss had not plateaued by 52 weeks, implying continued reductions.

Besides weight loss, MariTide improved hemoglobin A1c by up to 2.2%, lowered blood pressure, and improved lipid profiles.

The most common side effects were stomach-related, such as nausea, vomiting, and constipation. These were mostly mild and temporary, often happening after the first dose.

MariTide is now being studied further in the ongoing MARITIME Phase 3 clinical trial program.

Good to know:

Phase 2 Trials

These studies test whether a drug actually works in people who have the condition. They also continue monitoring safety and help determine the best dose. Phase 2 trials usually include a few hundred participants.

Phase 3 Trials

These are larger studies that confirm the drug’s effectiveness and monitor side effects in a much bigger group, often thousands of participants. Phase 3 compares the new drug to a placebo or an existing treatment. Results from Phase 3 are usually used to decide whether the FDA approves the drug.

4. Orforglipron

Orforglipron (LY3502970) is the first non-peptide, oral GLP-1 receptor agonist. Unlike peptide-based GLP-1 drugs that need fasting requirements, orforglipron is taken once daily without regard to meals.

The phase 3 ATTAIN 1 trial found that 36 mg orforglipron led to 12.4% mean weight loss (~27.3 lbs) at 72 weeks and improved blood pressure and non-HDL cholesterol. Lower doses (6 mg and 12 mg) also significantly reduced weight relative to placebo.

In the ATTAIN-MAINTAIN study, participants who had previously lost weight with injectable GLP-1 therapies (Wegovy or Zepbound) switched to orforglipron. They maintained almost all their prior weight loss, with differences of 0.9 kg after switching from Wegovy and 5.0 kg after switching from Zepbound.

In post-hoc analyses at 24 weeks, Wegovy switchers gained almost no weight, compared to about 9.4 kg gain in the placebo group. Zepbound switchers gained about 2.6 kg, compared to 9.1 kg with placebo.

The most common side effects were stomach-related, such as nausea or diarrhea, and were usually mild to moderate.

Orforglipron also received a fast-track review voucher from the FDA. This could shorten the approval review time to as little as one to two months, compared to the usual 10 to 12 months. However, the FDA later set a target decision date of April 10 for orforglipron.

5. VK2735

Viking Therapeutics’ VK2735 targets both GLP-1 and GIP receptors and is given once weekly. In the phase 2 VENTURE trial, participants receiving the highest dose lost 14.7% of their baseline body weight after only 13 weeks.

Weight loss trajectories showed no plateau, suggesting further reductions with longer treatment. The company is also developing an oral version (VK2735 tablets), which, in a small study, produced about 12% weight loss.

Viking initiated the Phase 3 VANQUISH 1 trial in June 2025, which has completed enrollment, and is moving quickly through late-stage studies.

6. Survodutide (BI 456906)

Survodutide, developed by Boehringer Ingelheim and Zealand Pharma, is a co-agonist of glucagon and GLP-1 receptors. By activating glucagon, survodutide raises energy expenditure, while GLP-1 agonism suppresses appetite.

In a phase 2 trial, different dose groups achieved mean body-weight reductions of:

  • 6.2% (0.6 mg)
  • 12.5% (2.4 mg)
  • 13.2% (3.6 mg)
  • 14.9% (4.8 mg)

This is compared with 2.8% body weight reduction for the placebo. Participants who escalated to 4.8 mg and maintained that dose experienced 18.7% weight loss at 46 weeks, and up to 40% achieved a weight loss of 20% or more.

Common adverse events were mild to moderate gastrointestinal symptoms, mostly during dose escalation.

Phase 3 trials evaluating survodutide for obesity and for metabolic dysfunction-associated steatohepatitis (MASH) are underway, with results anticipated by 2026.

7. Mazdutide

Mazdutide (Ibi362), co-developed by Innovent and Eli Lilly, combines glucagon and GLP-1 receptor agonism.

In the GLORY 1 phase 3 trial, Chinese adults with obesity were randomized to 4 mg or 6 mg mazdutide or placebo. At week 48, mean weight reductions were 12.0% (4 mg) and 14.8% (6 mg) compared with 0.5% for placebo. More than 80% of participants on 6 mg achieved a weight loss of 5% or more, and 50.6% achieved a weight loss of 15% or more, far exceeding placebo.

The study also reported reductions in waist circumference and liver fat. Mazdutide received approval in China in 2025, making it the first dual glucagon/GLP-1 agonist approved for chronic weight management. Innovent and Lilly are exploring global development, so mazdutide may become available outside China in the coming years.

8. Amycretin

Amycretin is Novo Nordisk’s dual agonist that mimics both GLP-1 and amylin. Mid-stage trials have shown that weekly injections of amycretin helped patients lose up to 14.5% of their body weight over 36 weeks, outperforming placebo. The oral formulation achieved up to 10.1% weight loss. No weight loss plateau suggests potential for further reductions with longer treatment.

Amycretin also significantly lowered blood glucose, with up to 89.1% of participants achieving HbA1c < 7%.

This therapy could offer a best-in-class alternative by leveraging two satiety hormones. Analysts estimate amycretin could reach peak sales of $8 billion by 2034. Novo Nordisk plans to initiate phase 3 trials in 2026.

9. Eloralintide

Eloralintide is Eli Lilly’s own amylin-based drug. Unlike amycretin, eloralintide is a selective amylin receptor agonist, meaning it mimics the satiety hormone amylin without GLP-1 activity. Researchers believe it may help people eat fewer calories by increasing feelings of fullness.

In a 48-week phase 2 trial, weight loss ranged from 9% at 1 mg to 20% at 9 mg doses, whereas the placebo group lost 0.4%. Participants reported mild to moderate nausea and fatigue that increased with dose but generally resolved over time.

Phase 3 clinical trials for eloralintide are currently in the initiation and setup phase, with trials expected to begin recruiting patients in early 2026.

10. Pemvidutide

Pemvidutide is developed by Altimmune and combines GLP-1 and glucagon receptor agonism. In the MOMENTUM phase 2 trial, adults with obesity who received weekly pemvidutide injections lost 10.3% (1.2 mg), 11.2% (1.8 mg), and 15.6% (2.4 mg) of their baseline weight at 48 weeks compared with 2.2% with placebo.

Body composition analysis also showed that only 21.9% of weight loss was attributable to lean mass, meaning pemvidutide predominantly reduced fat.

Altimmune plans to proceed to phase 3 trials focusing on obesity and metabolic dysfunction-associated steatohepatitis (MASH). The combination of significant weight loss and preservation of muscle mass could differentiate pemvidutide from other incretin therapies.

11. PF-08653944 (PF’3944)

PF-08653944, also called PF’3944 or MET-097i, is Pfizer’s ultra-long-acting GLP-1 receptor agonist designed for monthly dosing.

The phase 2b VESPER 3 trial investigated switching participants from weekly titration to monthly maintenance dosing. Topline results showed that at week 28, placebo-adjusted weight loss reached 10% and 12.3% in the low- and medium-dose arms, respectively.

Weight loss continued after the switch, with no plateau observed at 28 weeks. Gastrointestinal adverse events were mostly mild or moderate, and the drug maintained a favourable safety profile. Pfizer plans to include higher monthly doses in phase 3 trials starting in 2026.

Bottom line

The new weight loss drugs offer potent and flexible treatment options. Triple agonists like retatrutide are approaching 25% to 30% average weight loss in trials, while dual agents such as CagriSema, survodutide, mazdutide, and pemvidutide are delivering 15% to 23% reductions in many participants. Oral options like orforglipron and VK2735 tablets, along with monthly injectables such as MariTide and PF-08653944, may improve convenience and long-term adherence.

Most side effects remain gastrointestinal and are typically mild to moderate during dose escalation. Several candidates also improve blood sugar, blood pressure, and liver fat, expanding their metabolic impact beyond weight alone.

If ongoing Phase 3 data confirm current results and FDA approvals move forward, 2026 could usher in a new generation of obesity treatments with greater efficacy, more dosing choices, and broader personalization than ever before.

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Frequently Asked Questions

Retatrutide is still in Phase 3 clinical trials as of 2026 and has not yet been approved by the FDA. Eli Lilly expects trial completion in 2026, after which it would need to submit a New Drug Application. If approved, availability would likely occur after regulatory review, which typically takes several months. There is currently no official FDA approval date.

Safety depends on a person’s medical history and risk factors. Among FDA-approved oral options, orlistat (Alli/Xenical) has been available the longest and has an established safety record, though it commonly causes gastrointestinal side effects. Newer prescription oral agents, such as Wegovy tablets, are also available. A clinician should determine which option is safest for an individual.

Tirzepatide, marketed as Zepbound for obesity, has demonstrated greater average weight loss than semaglutide in clinical trials. In the SURMOUNT-1 study, participants lost up to 22.5% of body weight with tirzepatide. Experimental drugs such as retatrutide have shown even higher reductions in trials but are not yet approved.

Four commonly prescribed long-term FDA-approved medications for chronic weight management include orlistat, phentermine/topiramate extended-release (Qsymia), naltrexone/bupropion extended-release (Contrave), and liraglutide (Saxenda). Semaglutide (Wegovy) and tirzepatide (Zepbound) are also FDA-approved for obesity. These medications are intended to be used alongside lifestyle changes.

Based on average weight loss in clinical trials, tirzepatide (Zepbound, semaglutide (Wegovy), and high-dose phentermine/topiramate are among the most effective FDA-approved options. Tirzepatide has produced average reductions exceeding 20% in some studies. Semaglutide has shown about 15% average loss at 68 weeks. Individual outcomes vary depending on dose and adherence.

Both semaglutide (Ozempic) and tirzepatide (Mounjaro) have similar gastrointestinal side effects, such as nausea and diarrhea. Clinical trials show comparable safety profiles, though tirzepatide may cause slightly more GI symptoms at higher doses. Neither is considered universally safer. The choice depends on your health history and treatment goals.

Psyllium husk is often mentioned as a lower-cost alternative to Ozempic. It is a soluble fiber supplement commonly used for digestive support, including products like Metamucil. Some people promote it as a budget-friendly way to help with fullness and blood sugar control, but experts stress that it does not replicate the effects of prescription GLP-1 medications.

The only FDA-approved over-the-counter weight loss medication in the US is orlistat 60 mg (Alli). It typically results in modest weight loss of about 3% to 5% of body weight when combined with diet changes. Be cautious with supplements marketed as “fat burners,” as they are not FDA-approved for weight loss and lack strong clinical evidence.

There is no single best medication for everyone. Tirzepatide and semaglutide currently produce the greatest average weight reductions among approved drugs. But effectiveness depends on your medical conditions, tolerance, and long-term adherence. A healthcare provider can help you match the medication to your needs.

Clinical studies show that many people regain a significant portion of lost weight after stopping semaglutide. In an extension of the STEP 1 trial, participants regained about two-thirds of their prior weight loss within one year after discontinuation. This suggests ongoing treatment or sustained lifestyle changes may be needed to maintain results. Weight management is generally a long-term process.

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