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October 28, 2026

Beyond Tirzepatide: The New Weight-Loss Peptides Racing Toward FDA Approval

Retatrutide, amylin peptides, a monthly shot and more: where every new weight-loss peptide stands with the FDA, and how each compares with tirzepatide.

Beyond tirzepatide: the new weight-loss peptides racing toward FDA approval

Semaglutide and tirzepatide changed what weight loss looks like. Now a new wave of peptides is close behind, and some of the early numbers are remarkable: almost 29% average weight loss in one trial, a once-a-month shot, and peptides built to make you feel full instead of just less hungry. Here's every one worth knowing, where it stands with the FDA, and how it compares with what's approved today.

Peptide Advocate · Wellness and weight-loss coaches, drawing on a community of experienced users and backed by published research · Updated October 2026

What's comingPeptides that add a second or third hormone signal to GLP-1, plus amylin peptides and a monthly shot
Closest to approvalCagrilintide + semaglutide: filed with the FDA in December 2025, decision expected around now6
Biggest numbers so farRetatrutide: 28.7% average weight loss at 68 weeks in a phase 3 trial3
Legal statusNone of these new peptides is FDA approved yet. Mazdutide is approved in China only8

What the research says

Why a new wave is coming

Semaglutide copies one gut hormone, GLP-1. Tirzepatide copies two, GLP-1 and GIP, and that extra signal is a big part of why it beat semaglutide in trials: about 20.9% average weight loss at 72 weeks, against about 14.9% at 68 weeks for semaglutide.1,2 The next generation follows the same idea. Each new peptide adds or swaps in another of the body's own appetite and energy signals:

  • GLP-1 quiets hunger and slows how fast your stomach empties. It's the base of almost everything here.
  • GIP is a second gut hormone that seems to boost GLP-1's effect on weight and blood sugar.
  • Glucagon nudges the body to burn more energy and clear fat from the liver.
  • Amylin is released with insulin after meals and tells your brain you're full. It works through different brain pathways than GLP-1, which is why researchers hope it may bring fewer stomach side effects.

Which signals each peptide uses

PeptideGLP-1GIPGlucagonAmylinHow often
Semaglutide (approved)●Weekly or daily tablet
Tirzepatide (approved)●●Weekly
Retatrutide●●●Weekly
Cagrilintide + semaglutide●●Weekly
Amycretin●●Weekly or daily pill
Eloralintide, petrelintide●Weekly
Survodutide, mazdutide, pemvidutide●●Weekly
Maridebart cafraglutide●blocksMonthly

Maridebart cafraglutide is the odd one out: it boosts GLP-1 but blocks the GIP receptor, and it's an antibody with two peptides attached rather than a peptide on its own. That design is what lets it last a month.11

Where each one stands with the FDA

A new peptide has to pass through phase 2 trials (a few hundred people, to find the right dose) and phase 3 trials (thousands of people, to confirm it works and spot side effects) before a company can file with the FDA. A standard FDA review then takes about 10 months. Here's where everything sits today.

Where the new weight-loss peptides stand with the FDA Four columns from phase 2 to FDA approved. Phase 2: petrelintide, pemvidutide. Phase 3: retatrutide, survodutide, mazdutide (approved in China), eloralintide, amycretin, maridebart cafraglutide. Filed: cagrilintide plus semaglutide. Approved: semaglutide, tirzepatide, and orforglipron, which is not a peptide. The pipeline, from trials to approval FDA stage for weight management in the US, as of October 26, 2026 PHASE 2 Mid-size trials Petrelintide Amylin Pemvidutide Glucagon + GLP-1 PHASE 3 Large final trials Retatrutide Filing planned early 2027 Survodutide Positive results, 2026 Mazdutide Approved in China Eloralintide Amylin Amycretin Amylin + GLP-1 Maridebart cafraglutide Once a month FILED WITH FDA Under review Cagrilintide + semaglutide · decision due FDA APPROVED For weight loss Semaglutide Weekly shot, daily tablet Tirzepatide Weekly shot Orforglipron* Daily pill, not a peptide *Orforglipron is a small-molecule pill, not a peptide. Mazdutide is approved in China but has not been filed in the US.
Sources: company releases and trial publications listed below.3,4,6,8,12,14 Illustration: Peptide Advocate.

How they compare with semaglutide and tirzepatide

Three new peptides topped tirzepatide in their best trial Bar chart of average weight loss: retatrutide 28.7 percent, cagrilintide plus semaglutide 22.7, amycretin 22.0, eloralintide 20.1, maridebart cafraglutide 19.9, survodutide 16.6, pemvidutide 15.6, mazdutide 14.8, petrelintide 10.7. Dashed lines mark semaglutide at 14.9 and tirzepatide at 20.9 percent. Three new peptides topped tirzepatide in their best trial Average weight lost at the best dose tested, main trial so far Semaglutide 14.9% Tirzepatide 20.9% Retatrutide Phase 3 · 68 weeks 28.7% Cagrilintide + semaglutide Phase 3 · 68 weeks 22.7% Amycretin Early trial · 36 weeks 22.0% Eloralintide Phase 2 · 48 weeks 20.1% Maridebart cafraglutide Phase 2 · 52 weeks 19.9% Survodutide Phase 3 · 76 weeks 16.6% Pemvidutide Phase 2 · 48 weeks 15.6% Mazdutide Phase 3 · 48 weeks 14.8% Petrelintide Phase 2 · 42 weeks 10.7% Trials differ in length, size and who took part, so treat this as a rough guide, not a ranking.
Sources: STEP 1, SURMOUNT-1 and the trials of each new peptide.1,2,3,5,7,8,9,10,11,12,13 Illustration: Peptide Advocate.
28.7%average weight lost on retatrutide at 68 weeks in TRIUMPH-4, a phase 3 trial in people with obesity and knee arthritis3
22.7%average weight lost on cagrilintide + semaglutide at 68 weeks, vs. 16.1% on semaglutide alone5,6
13shots a year for maridebart cafraglutide, dosed once a month, vs. 52 for a weekly peptide11
4.8%of people on the most effective petrelintide dose stopped for side effects, about the same as placebo (4.9%)12

The peptides to watch

Here's the short version of each, from closest to approval to furthest away. Every number comes from a trial, and your results could be higher or lower.

1

Cagrilintide + semaglutide

Semaglutide plus a long-acting amylin peptide, in one weekly shot.

Filedwith the FDA, December 2025
22.7%average loss at 68 weeks

In REDEFINE 1, a 68-week trial of 3,417 adults, the combination beat both of its parts: 22.7% average weight loss, against 16.1% for semaglutide alone and 11.8% for cagrilintide alone, for people who stayed on treatment.5,6 The FDA decision was expected around October 2026; none had been announced when we published. In a head-to-head trial with tirzepatide 15 mg, it reached 23% but didn't prove it was at least as good.6

Read the deep dive on cagrilintide + semaglutide →

2

Retatrutide

The first "triple" peptide: GLP-1, GIP and glucagon in one weekly shot.

Phase 3filing planned early 2027
28.7%average loss at 68 weeks

Retatrutide has the biggest numbers in the pipeline. In TRIUMPH-4, people on the highest dose lost 28.7% of their weight on average, and about 1 in 4 lost 35% or more.3 Two more phase 3 trials, in people with type 2 diabetes and people with heart disease, reached 20.8% and 22.6% at 80 weeks.4 The trade-off to watch: about 18% of people on the highest dose stopped because of side effects in TRIUMPH-4, against 4% on placebo.3

Read the deep dive on retatrutide →

3

The amylin peptides

Eloralintide, amycretin and petrelintide work on feeling full.

Phase 2–3three peptides in trials
Up to 22%in early trials

Eloralintide uses amylin alone and reached 20.1% average weight loss at 48 weeks in a phase 2 trial of 263 adults.9 Amycretin combines amylin and GLP-1 in a single molecule: 22.0% at 36 weeks in a small early trial, with a daily pill version in testing too.10 Petrelintide aims lower, about 10.7% at 42 weeks, but with less vomiting than placebo.12

Read the deep dive on the amylin peptides →

4

The glucagon peptides

Survodutide, mazdutide and pemvidutide pair glucagon with GLP-1.

Phase 3mazdutide approved in China
15–17%average loss

These land closer to semaglutide on weight: 16.6% at 76 weeks for survodutide, 14.8% at 48 weeks for mazdutide and 15.6% at 48 weeks for pemvidutide.7,8,13 Their extra selling point is liver fat. In one survodutide trial, 84% of people cut their liver fat by at least 30%.7

Read the deep dive on the glucagon peptides →

5

Maridebart cafraglutide

An antibody-peptide hybrid designed to be taken once a month.

Phase 3first results expected 2027
Up to 19.9%average loss at 52 weeks

In a 52-week phase 2 trial of 592 adults, people without diabetes who stayed on treatment lost 16.3% to 19.9% on average; counting everyone, it was 12.3% to 16.2%.11 Nausea and vomiting were common, especially early, and starting at a lower dose helped. The main phase 3 trials are due to finish in early 2027.15

Read the deep dive on maridebart cafraglutide →

6

And one that isn't a peptide: orforglipron

A daily GLP-1 pill made from a small molecule, not a peptide.

FDA approvedApril 1, 2026
Up to 12.4%average loss at 72 weeks

You'll hear about orforglipron alongside the peptides because it switches on the same GLP-1 receptor. It's a small chemical molecule rather than a peptide, so it can be swallowed with no food or water rules. The FDA approved it for chronic weight management on April 1, 2026, after a trial showing up to 12.4% average weight loss at 72 weeks.14 That's less than the injectable peptides, but some people will prefer a pill.

Risks to keep in mind

Almost every peptide here causes the same side effects as semaglutide and tirzepatide: nausea, vomiting, diarrhea and constipation, mostly early on and after dose increases. The newer combinations add their own questions. Glucagon can raise heart rate and blood sugar, which is why it's always paired with GLP-1. In retatrutide's heart-disease trial, the number of heart events wasn't clearly higher or lower than with placebo, so that question is still open.4 And none of these peptides has the years of real-world safety data that semaglutide now has.

Before you get excited

Trial averages aren't your results. Each number above is an average from a controlled trial, with diet and activity counseling. Some people lose much more, some much less.

Not approved means no approved dose. Until the FDA approves a peptide, there's no official label telling anyone how to dose it, and long-term safety is still being studied.

Whatever you decide, don't keep your physician in the dark. Let them know what you're taking and any changes you make.

Want to take part in a trial? Many of these peptides are still recruiting volunteers. You can search for studies near you on ClinicalTrials.gov by typing the peptide's name.

The bottom line

The next few years look exciting for anyone working on their weight. Cagrilintide + semaglutide could be the next approval, retatrutide is aiming past anything approved today, and amylin peptides and a monthly shot could make treatment easier to live with. None of these new peptides is approved yet, and the numbers are trial averages. But the direction is clear: more options, more ways to match a peptide to the person. Whatever comes next, the habits that protect your muscle and keep weight off will still matter.

Been part of a trial, or following one closely? We learn from people living it. Share your experience with these new peptides in From Our Community, and help shape what we write next.

References

  1. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021;384:989–1002. nejm.org
  2. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. 2022;387:205–216. nejm.org
  3. pharmaphorum. Lilly's obesity triple pulls off 29% weight loss in trial (TRIUMPH-4 topline results); December 11, 2025. pharmaphorum.com
  4. Eli Lilly and Company. Lilly's triple agonist retatrutide successful in two additional phase 3 obesity trials (TRIUMPH-2 and TRIUMPH-3); July 23, 2026. biospace.com
  5. Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1). N Engl J Med. 2025. nejm.org
  6. Drugs.com. Cagrilintide and semaglutide: FDA approval status and history. Accessed October 26, 2026. drugs.com
  7. Cleveland Clinic Journal of Medicine. ADA 2026: survodutide and weight (SYNCHRONIZE-1 results); June 2026. ccjm.org
  8. Ji L, Jiang H, et al. Once-weekly mazdutide in Chinese adults with obesity or overweight (GLORY-1). N Engl J Med. 2025;392:2215–2225. nejm.org
  9. Billings LK, et al. Phase 2 trial of once-weekly eloralintide in adults with obesity or overweight. Lancet. 2025. doi.org
  10. Novo Nordisk. Subcutaneous and oral amycretin data published in The Lancet (Dahl K, et al.; Gasiorek A, et al.); June 2025. santelog.com
  11. Jastreboff AM, Ryan DH, Bays HE, et al. Once-monthly maridebart cafraglutide for the treatment of obesity: a phase 2 trial. N Engl J Med. 2025. nejm.org
  12. Roche. Positive phase II results for petrelintide (ZUPREME-1); March 5, 2026. roche.com
  13. Altimmune. Positive topline results from MOMENTUM 48-week phase 2 obesity trial of pemvidutide; November 30, 2023. biospace.com
  14. Healio. FDA approves orforglipron, an oral GLP-1 for adults with obesity; April 1, 2026. healio.com
  15. The Rx Index. Maridebart cafraglutide: phase 2 results and phase 3 (MARITIME) status. Accessed October 26, 2026. therxindex.com

Wellness & weight-loss coaches. We sell coaching. No sponsors, no affiliate links. Peptide Advocate takes no money or free product from peptide makers, sellers, compounders or clinics.

This content is for education only and isn't medical advice. It reflects the shared experience of our community, not the views of doctors or other medical professionals. Peptides can have serious side effects and many aren't FDA-approved. Don't keep your physician in the dark: let them know what you take and any changes you make. Information is current as of October 26, 2026. Charts and illustrations are original works by Peptide Advocate, simplified from published trial data.