Weight-loss peptides
Peptides for weight loss: the split most sites won't state
Six compounds get marketed under this exact phrase, and most pages that rank for it treat all six as interchangeable options on one list. They aren't. Two of them — tirzepatide and semaglutide — are FDA-approved and have real, randomized, controlled trial evidence of weight loss specifically. The other four are not approved for this, each for a different reason, and this page states which reason applies to which compound rather than folding all four into one vague “emerging” category.
This is not a top-10 ranking. It's a re-view of content this site has already published and independently verified — linked below by compound — organized by the one distinction that actually matters before any other comparison: can you legally get a prescription for this, and does a controlled trial say it works for weight loss specifically.
The split, stated plainly
Read straight down this list and the pattern is the entire point of the page: the tier a compound lands in is set by its regulatory and trial status, not by which one produced the most dramatic number in a press release.
- TirzepatideGIP/GLP-1 dual agonist, approved as Zepbound — the larger effect in the only head-to-head trial run.Tier A — FDA-approved, trial-proven for weight loss
- SemaglutideGLP-1 agonist, approved as Wegovy — the original trial-proven weight-loss GLP-1.Tier A — FDA-approved, trial-proven for weight loss
- TesamorelinApproved as Egrifta — but for HIV-associated lipodystrophy. Its own label says "weight neutral."Tier B — FDA-approved, but not for this
- CagrilintideReal Phase 3 data, published — but alone, it underperformed semaglutide in its own trial.Tier C — investigational, real trial data, no approval
- RetatrutideThe biggest number on this page — and a compound with no legal purchase pathway at all.Tier C — investigational, real trial data, no approval
- MOTS-cReal mouse data and a real mechanism — no completed human trial ever dosed it for weight loss.Tier D — no completed human dosing trial
How we ordered this
Same standard as our editorial policy — the rule is published here, in full, so it can be checked rather than taken on faith:
- Tier A — FDA-approved for weight loss, with randomized controlled trial evidence in that indication. Only tirzepatide (Zepbound) and semaglutide (Wegovy) clear this. Within the tier, the one randomized head-to-head trial between them — not either drug's separate placebo trial — decides the order.
- Tier B — FDA-approved product exists, but not for weight loss. Tesamorelin has a real, current approval; its own label states the approved use is weight-neutral. An approval for a different indication doesn't transfer to this one, so it sits in its own tier rather than beside Tier A.
- Tier C — no FDA-approved product, but real randomized controlled human trial evidence exists. Cagrilintide and retatrutide both qualify. Between the two, the tiebreak is which compound's strongest human evidence has cleared full peer review, not which reported the bigger number: cagrilintide's pivotal trial (REDEFINE-1) is a completed, published, peer-reviewed Phase 3 NEJM paper; retatrutide's Phase 3 program has completed trials, but as of this writing their results are reported only as topline press-release figures, with retatrutide's own highest fully peer-reviewed evidence still at Phase 2. Cagrilintide is listed first on that basis.
- Tier D — no FDA-approved product, and no completed human trial dosing the compound itself for weight loss. MOTS-c is the only compound here with real published human data that is entirely observational (measuring a person's own naturally occurring peptide level) rather than interventional (a trial that actually administered synthetic MOTS-c to a person and measured a weight-loss outcome).
One consequence of ranking this way, worth stating rather than hiding: the single largest reported effect size on this whole page belongs to retatrutide (Tier C) — a compound with no FDA approval and no legal purchase pathway today. A bigger trial number does not move a compound ahead of one that's actually approved and prescribable. That is not an oversight; it is the entire reason this page is organized this way instead of by effect size.
Tier A — FDA-approved, trial-proven for weight loss
Tirzepatide
Tirzepatide activates two hormone receptors at once — GIP and GLP-1 — rather than the one target semaglutide works on. It is FDA-approved for chronic weight management as Zepbound (Eli Lilly), confirmed directly against FDA's own Drugs@FDA record, which lists the product's marketing status as “Prescription”.
The direct, randomized head-to-head trial against semaglutide — SURMOUNT-5 — put 751 adults with obesity, no type 2 diabetes, on either drug at its own maximum tolerated dose, for 72 weeks. The result: -20.2% body weight with tirzepatide versus -13.7% with semaglutide (P<0.001), the same direction as tirzepatide's own earlier placebo-controlled trial, SURMOUNT-1 (-20.9% at 15 mg vs. -3.1% placebo). That is genuine, randomized, peer-reviewed evidence of superiority in the drug class this page is actually about, not a cross-trial guess.
For the full evidence review, the legal status of compounded versions, the FDA label's dosing ladder, and reported side effects, this site already has independently verified, separately dated coverage: the full tirzepatide-vs-semaglutide trial review, whether compounded tirzepatide is still legal, the FDA label's dosage chart and what the trials reported on side effects. Ready to compare providers? Our tirzepatide provider board ranks pharmacy disclosure and price, live-checked, and our reconstitution calculator does the vial-to-syringe math once you have a prescribed dose.
Sources: Aronne LJ et al., “Tirzepatide as Compared with Semaglutide for the Treatment of Obesity,” NEJM, 2025 (PMID 40353578); Jastreboff AM et al., “Tirzepatide Once Weekly for the Treatment of Obesity,” NEJM, 2022 (PMID 35658024); FDA Drugs@FDA record for ZEPBOUND (openFDA API). All re-verified live August 2026.
Semaglutide
Semaglutide activates the GLP-1 receptor alone. It is FDA-approved for chronic weight management as Wegovy (Novo Nordisk), confirmed the same way — a live Drugs@FDA query lists the product's marketing status as “Prescription”. It was the first GLP-1 drug to establish this drug class's weight-loss evidence at scale: STEP 1 randomized adults with overweight or obesity to semaglutide 2.4 mg or placebo and reported -14.9% body weight at 68 weeks versus -2.4% for placebo — the trial SURMOUNT-1 and SURMOUNT-5 are directly measured against above.
SURMOUNT-5's head-to-head result (above) found tirzepatide produced significantly more weight loss than semaglutide in the same trial, at each drug's own maximum dose — that is why semaglutide sits second within Tier A, not because its own evidence is weak. It is still a real, FDA-approved, randomized-trial-proven weight-loss drug, and for some patients — different tolerability, a lower escalation ceiling, or a provider's specific roster — it remains the right choice independent of which drug “won” one comparative trial.
For the full picture: what compounded semaglutide actually is, whether it's still legal to compound, and the FDA label's dosage chart. Compare providers on our semaglutide board — or if you haven't settled on a drug class yet, our combined weight-loss-injections ranking merges the tirzepatide and semaglutide rosters into one list, each provider shown once at whichever price is lower.
Sources: Wilding JPH et al., “Once-Weekly Semaglutide in Adults with Overweight or Obesity,” NEJM, 2021 (PMID 33567185); FDA Drugs@FDA record for WEGOVY (openFDA API). Re-verified live August 2026.
Tier B — FDA-approved, but not for this
Tesamorelin
Tesamorelin has a real, current FDA approval — but not for weight loss. Both current labels (Egrifta SV, Egrifta WR) approve it for exactly one use: reduction of excess abdominal fat in HIV-infected adults with lipodystrophy, and both state directly that tesamorelin “is not indicated for weight loss management as it has a weight neutral effect.”
The trial evidence behind that approval is genuinely strong, for the population it was tested in: a pooled analysis of two multicenter, double-blind, placebo-controlled Phase 3 trials in 806 HIV-infected patients found visceral adipose tissue fell -24% with tesamorelin against +2% with placebo (P<0.001) at 26 weeks. That is a real reduction in a specific fat depot, in a specific clinical population, on a growth-hormone-releasing-hormone mechanism — not a general weight-loss result, and not evidence this page extends to anyone outside that indication.
This site tracks providers for one growth-hormone-axis compound: sermorelin. Tesamorelin is not sold by any provider on that roster, and shouldn't be presented as if it were — its only approved use is the HIV-lipodystrophy indication above, not general wellness or weight management. Our sermorelin board is the GH-axis compound this site actually ranks providers for.
For the full head-to-head against sermorelin, the FDA label's exact dosing, and reported side effects: sermorelin vs. tesamorelin, what the evidence shows, tesamorelin side effects, and our tesamorelin reconstitution calculator.
Source: Falutz J et al., “Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in HIV-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials,” J Clin Endocrinol Metab, 2010 (PMID 20554713). Re-verified live August 2026.
Tier C — investigational, real trial data, no approval
Cagrilintide
Cagrilintide is an amylin-receptor analog — a different mechanism entirely from the GLP-1/GIP compounds above — developed by Novo Nordisk and best known as half of CagriSema, its fixed-dose combination with semaglutide. The finding most cagrilintide marketing skips: in REDEFINE-1, Novo Nordisk's own 3,417-person Phase 3 trial, cagrilintide taken alone lost 11.8% of body weight at 68 weeks, while semaglutide taken alone — in the very same trial — lost 16.1%. Cagrilintide beat placebo by a wide margin, but it was the weaker of the two monotherapies the trial actually tested it against.
Regulatory status matters here in a way that's easy to blur: cagrilintide by itself has never been filed with FDA. What Novo Nordisk filed, in December 2025, is the CagriSema combination — a patented, fixed-dose product a compounding pharmacy cannot lawfully replicate. A compounded vial sold as “cagrilintide” is, at best, the weaker 11.8% monotherapy arm — never the combination's 22.7% result some marketing borrows.
For the full REDEFINE-1/2/5 trial breakdown, both statistical estimands reported, and the exact FDA filing timeline: our full cagrilintide evidence review. No provider on this site's boards sells it under a ranked comparison — this site investigated and ruled out a cagrilintide board rather than publishing a thin one. If you already have a prescribed dose in hand, our reconstitution calculator does the arithmetic — pure math on what you type in, not a check on the product itself.
Source: Garvey WT et al., “Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity,” NEJM (REDEFINE 1), 2025 (PMID 40544433). Re-verified live August 2026.
Retatrutide
Retatrutide is a triple hormone-receptor agonist — GIP, GLP-1, and glucagon at once, the added glucagon activity being the mechanistic reason for its size advantage in trials so far. Its Phase 2 data, published in NEJM, is the largest reported weight-loss effect of any compound on this page: -24.2% at 48 weeks on the 12 mg dose, against -2.1% for placebo.
None of that makes it available. A live query against FDA's own Drugs@FDA database returns zero matches for “retatrutide” — confirmed the same way this page confirmed Zepbound and Wegovy's approvals actually resolve, by re-running the identical query mechanism against a drug that does have records. Eli Lilly's own press materials state plainly that retatrutide “is an investigational molecule that cannot be legally sold or marketed for human use,” with a BLA filing planned for the first quarter of 2027 — a planned filing, not a pending decision.
“Buy retatrutide” searches still return real product pages — this site's own investigation found DailyMed structured-product-label filings for retatrutide-branded injectables from an unregulated cross-border seller, and an actual March 2026 FDA warning letter naming retatrutide among products sold despite “Research Use Only” labeling. Read the full investigation, including exactly what those searches find and why it's a different legal situation than compounded tirzepatide, in our full retatrutide status review. There is no board comparison for retatrutide on this site, for the same reason there is no legal product to compare: no FDA-approved reference product means no 503A compounding exception exists for it. Our reconstitution calculator exists for readers who already have vial numbers to work with — it validates nothing about the product itself.
Source: Jastreboff AM et al., “Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial,” NEJM, 2023 (PMID 37366315). Re-verified live August 2026.
Tier D — no completed human dosing trial
MOTS-c
MOTS-c is genuinely unusual among peptides sold for weight loss: it's encoded inside mitochondrial DNA rather than the cell's nuclear genome, discovered in 2015 as a 16-amino-acid signal that, in mice, “prevented age-dependent and high-fat-diet-induced insulin resistance, as well as diet-induced obesity”. That's the real mechanistic story, and it's also entirely animal data.
No completed human trial has ever administered synthetic MOTS-c to a person and measured a weight-loss outcome. Real published human studies exist, but every one of them measures a person's own naturally occurring MOTS-c level in blood or muscle — usually before and after exercise — never a dosed, synthetic peptide. The one completed human interventional trial in this discovery lineage dosed a different molecule (CB4211, a separate company's own analog) for a different condition than weight loss.
No FDA-approved MOTS-c product exists — a live DailyMed structured-product-label search returns zero results for “MOTS-C.” It was reviewed at FDA's July 2026 Pharmacy Compounding Advisory Committee meeting for compounding-substance status, not for a drug approval, and that review process is a separate question from whether it works — this site's own full evidence review covers that vote and every human study located, exercise study by exercise study, rather than collapsing “real human data exists” and “a human trial proved it works” into the same claim.
Read the complete breakdown — mouse data, every human observational study located, and exactly what the CB4211 distinction means — in our full MOTS-c evidence review. No board ranks providers for it. Our reconstitution calculator covers the arithmetic only.
Source: Lee C, Zeng J, Drew BG, et al., “The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance,” Cell Metabolism, 2015 (PMID 25738459). Re-verified live August 2026.
All six, side by side
The facts that actually decide whether you can legally get a prescription — not prices, which move daily and live on the linked cost pages instead, re-checked on their own schedule.
| Compound | FDA-approved product? | Approved for weight loss? | Strongest human evidence | Board on this site? |
|---|---|---|---|---|
| Tirzepatide | Yes — Zepbound | Yes | Randomized head-to-head win (SURMOUNT-5) | Yes — ranked |
| Semaglutide | Yes — Wegovy | Yes | Randomized placebo trial (STEP 1) + head-to-head runner-up | Yes — ranked |
| Tesamorelin | Yes — Egrifta | No — HIV lipodystrophy only | Pooled Phase 3 RCT, 806 patients (different indication) | No — ADJACENT to sermorelin board |
| Cagrilintide | No — only CagriSema combo is filed | No | Published Phase 3 RCT (REDEFINE-1) — monotherapy arm | No — investigated, not built |
| Retatrutide | No | No | Published Phase 2 RCT; Phase 3 topline only, not yet published | No — investigated, not built |
| MOTS-c | No | No | Human data is observational only; no interventional weight-loss trial | No board |
Actual, current prices move daily and are read directly off each provider's own site on the date shown there — see the cost-first views for tirzepatide and semaglutide, or every board's prices aggregated into one table on the cross-board pricing index. Wondering whether insurance covers any of this? our insurance-coverage explainer covers that separately, since coverage depends on diagnosis and plan, not on which compound you pick from this page.
How to actually choose, once you know the split
- Start with prescribability, not marketing. If a compound isn't in Tier A, no clinic's copy changes what FDA has and hasn't approved it for. That's a fact you can check yourself the same way this page did — a live query against Drugs@FDA or DailyMed, not a vendor's claim.
- Match the indication, not just the mechanism. Tesamorelin's approval is real and its trial data is strong — for a specific HIV-related condition its own label says is “weight neutral.” A shared growth-hormone-axis mechanism with sermorelin doesn't make it a weight-loss drug.
- Read which arm a number came from. Cagrilintide's own trial reported both an 11.8% monotherapy result and a 22.7% combination result — only the first describes what a compounding pharmacy can lawfully sell alone.
- Separate mixing and injecting from choosing a compound. Once you and a licensed clinician have settled on one, this site's handling and storage guide covers bacteriostatic water, reconstitution, and injection technique — none of it dosing advice, all of it sourced from FDA labeling and CDC guidance.
- Talk to a licensed clinician before starting anything. Nothing on this page is a recommendation to use any specific compound, at any dose.
Medical disclaimer: This content is for general educational purposes only and is not medical advice, diagnosis, or treatment. Always consult a licensed healthcare professional before starting, stopping, or changing any treatment.
This page describes FDA approval status and published trial evidence. It does not recommend a dose, a compound, or a provider for any individual, and it is not a substitute for a licensed clinician's judgment. Read our full medical disclaimer.
Every FDA/PubMed source on this page was fetched and independently verified live on August 2026.