Verified July 2026 · Cited to primary sources
Every peptide marketed for fat loss, graded by human evidence and legal status. The best are the FDA-approved GLP-1 medications, semaglutide and tirzepatide (Grade A); we grade them here and route you to a provider comparison. The research peptides sold for fat loss do not beat them.
Evidence for this goal
The GLP-1 medications semaglutide and tirzepatide (Grade A, FDA-approved) are the evidence-backed answer, and we point you to a provider comparison for them. Tesamorelin (Grade A) is approved only for HIV-associated visceral fat, not general weight loss. Retatrutide (Grade B) is investigational. MOTS-c is Grade D.
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How to read this comparison
Compounds are listed alphabetically, not ranked for this goal. The overall grade reflects the evidence described in each record. Evidence for one condition, population or product form does not establish benefit for every use. Affiliate availability never changes a grade.
A historical FDA survey of compounded drugs found 31% failed standard potency testing. What is actually in the vial is a separate question from whether the compound works, and a rubric like this exists to keep the two apart. See the full A to F methodology →
Evidence scope: This is the rare peptide that was actually taken into a large, adequately-powered human efficacy trial and lost. Metabolic Pharmaceuticals ran a 24-week Phase 2b study (METAOD006) in roughly 500 obese adults across multiple oral doses versus placebo, and it did not produce a statistically significant weight-loss difference over placebo on the primary endpoint. Development was terminated in 2007. Earlier short (12-week) data hinted at a tiny effect (about 2.6 kg vs 0.8 kg placebo) that did not hold up when properly tested for longer in more people. Human safety data is reassuring but efficacy was disproven, which is the definition of a grade F: tested in humans, failed.
Sources: Stier et al. 2013, J Endocrinol Metab - Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans (pooled analysis of six randomized placebo-controlled trials, ~900 participants; confirms good tolerability but is a safety, not efficacy, paper) · BioSpace 2007 - Metabolic Pharmaceuticals Obesity Trial Update on the Phase 2b AOD9604 program (documents the 24-week Phase 2b design and dosing that ultimately failed the primary weight-loss endpoint)
AOD-9604 is a synthetic analog of the C-terminal region (amino acids 176-191) of human growth hormone, with a tyrosine added at the N-terminus. In rodent and in-vitro work it was reported to stimulate lipolysis (fat breakdown) and inhibit lipogenesis by acting on beta-3 adrenergic pathways in fat tissue, apparently without the blood-sugar-raising or growth-promoting effects of full-length HGH. That mechanism never translated into meaningful human fat loss.
AOD-9604 is the cautionary tale of the fat-loss peptide world. It sounds elegant on paper, it has clean human safety data, and it completely failed the 24-week Phase 2b obesity trial it was designed to win. It is not FDA approved, it is banned in sport, and no amount of clinic marketing changes the fact that the pivotal human study did not beat placebo. If your goal is weight loss, the GLP-1 class has real outcome data; AOD-9604 does not.
See the evidence →Evidence scope: Not FDA-approved. Evidence rests on positive human trials short of standalone approval. A phase 2 dose-finding trial showed cagrilintide 4.5 mg produced about 10.8 percent weight loss at 26 weeks versus 3.0 percent on placebo, and beat liraglutide 3.0 mg. In the phase 3 REDEFINE 1 trial the CagriSema combination reached roughly 20 percent weight loss. Strong phase 2 and 3 human data, but no standalone approval, so grade B.
Sources: Once-weekly cagrilintide for weight management: a phase 2 dose-finding trial (Lancet 2021, PMID 34798060) · REDEFINE 1: Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (NEJM 2025, PMID 40544433)
A long-acting analog of amylin, the pancreatic hormone co-secreted with insulin. It acts on amylin and calcitonin receptors to slow gastric emptying, suppress glucagon, and promote satiety through a pathway distinct from GLP-1. The interest is in stacking it with a GLP-1 agonist (semaglutide) to hit two separate appetite mechanisms at once, which is the CagriSema strategy.
Grade B and genuinely promising, but the key fact is that it is not FDA-approved as a standalone drug. The real-world path for cagrilintide is as the amylin half of the CagriSema combination, which posted roughly 20 percent weight loss in phase 3. If you want something you can actually get today, that means an approved GLP-1: see glp1picks.com for those. Do not source cagrilintide from research-chemical vendors.
See the evidence →Evidence scope: FDA-approved for type 2 diabetes with a large phase 3 base. The REWIND cardiovascular outcomes trial in 9,901 patients showed a 12 percent relative reduction in major cardiac events over a median 5.4 years, one of the longest GLP-1 outcomes trials. AWARD-11 established the higher 3.0 and 4.5 mg doses, with weight loss of about 4.6 kg at 4.5 mg. Grade A as a diabetes and cardiovascular drug; note it is not approved specifically for obesity.
Sources: REWIND: Dulaglutide and Cardiovascular Outcomes in Type 2 Diabetes (Lancet 2019, PMID 31189511) · AWARD-11: Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus 1.5 mg in Type 2 Diabetes (Diabetes Care 2021, PMID 33397768)
A GLP-1 analog fused to an antibody Fc fragment, which extends its half-life to roughly 5 days and enables weekly dosing. It activates GLP-1 receptors to increase glucose-dependent insulin secretion, suppress glucagon, slow gastric emptying, and modestly reduce appetite. The Fc-fusion design is what distinguishes it structurally from semaglutide and liraglutide.
Grade A as a diabetes and cardiovascular drug, but the honest caveat is that it is not FDA-approved for obesity and produces less weight loss than semaglutide or tirzepatide. If weight is your only goal, a dedicated obesity agent is the better tool. If you have type 2 diabetes and cardiovascular risk, it is an excellent choice. We grade the molecule here; for provider comparison and access, see glp1picks.com, our sister site.
See the evidence →Evidence scope: FDA-approved for chronic weight management (3.0 mg) and type 2 diabetes (up to 1.8 mg), with a large phase 3 evidence base. The SCALE Obesity and Prediabetes trial showed a mean 8.4 kg loss at 56 weeks versus 2.8 kg on placebo. The LEADER cardiovascular outcomes trial in 9,340 patients showed a 13 percent relative reduction in major cardiac events. Solid grade A, just outperformed on weight by the newer weekly agents.
Sources: SCALE: A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (NEJM 2015, PMID 26132939) · LEADER: Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (NEJM 2016, PMID 27295427)
A once-daily GLP-1 analog with about 97 percent homology to native GLP-1 and a fatty-acid chain that extends its half-life to roughly 13 hours. It works through the same GLP-1 pathway as semaglutide (insulin secretion, slowed gastric emptying, central satiety) but requires daily dosing and produces more modest weight loss.
Grade A on the science, but in 2026 it is largely a legacy option: the daily injection and smaller weight effect make semaglutide or tirzepatide the usual first choice unless there is a specific reason to prefer it. If you and your prescriber land on liraglutide, we grade the molecule here and hand off the shopping. For provider comparison and where to get it, see glp1picks.com, our sister site.
See the evidence →Evidence scope: Grade D: preclinical plus early human observational/biomarker studies, no efficacy RCT (rule 5 fired).
Sources: FDA PCAC July 23-24, 2026 meeting (docket) · RAPS: FDA advisory committee backs controversial peptides (July 23, 2026 vote coverage) · Federal Register FDA-2025-N-6895 (April 2026 503A reclassification)
Mitochondrial-derived "exercise mimetic" that activates AMPK to improve insulin sensitivity and metabolic homeostasis in preclinical models.
MOTS-c is not FDA-approved and is not yet legal to compound. On July 23, 2026 the FDA's PCAC panel voted 7 to 5 (2 abstentions) to recommend adding it to the 503A list for weight loss, overriding the FDA's own scientists, but the FDA still decides and has not acted. Human evidence stays Grade D: metabolic effects are mostly preclinical, with human data limited to associations. For actual weight loss, an approved GLP-1 is the evidence-backed route.
See the evidence →Evidence scope: Grade B: real human trial data (published Phase 2 obesity/T2D RCTs) but not yet FDA-approved and Phase 3 ongoing (rule 3: real human clinical trials, limited/not-yet-approved). We hold it at B rather than A because approval is not final.
Sources: Jastreboff et al., N Engl J Med 2023: retatrutide Phase 2 obesity RCT (24.2% at 48 wk)
A triple agonist of the GIP, GLP-1 and glucagon receptors that suppresses appetite and raises energy expenditure to drive weight loss.
Retatrutide is investigational (Phase 3), not FDA-approved, and not legally available. Human evidence is Grade B: strong published Phase 2 weight-loss data, but not a finished approval. For proven weight loss you can access legally today, see our GLP-1 guidance.
See the evidence →Evidence scope: FDA-approved for chronic weight management and type 2 diabetes, backed by multiple large phase 3 randomized controlled trials. STEP 1 showed a mean 14.9 percent body-weight reduction at 68 weeks versus 2.4 percent on placebo. SELECT, a 17,604-patient cardiovascular outcomes trial, showed a 20 percent relative reduction in major cardiac events. This is as strong as human evidence gets for a peptide.
Sources: STEP 1: Once-Weekly Semaglutide in Adults with Overweight or Obesity (NEJM 2021, PMID 33567185) · SELECT: Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (NEJM 2023, PMID 37952131)
A long-acting analog of glucagon-like peptide-1 (GLP-1). It binds GLP-1 receptors in the pancreas, brain, and gut to boost glucose-dependent insulin secretion, slow gastric emptying, and reduce appetite through central satiety signaling. The 2.4 mg weekly dose is what drives the weight-loss effect; lower doses are used for type 2 diabetes.
Grade A, and the reference standard for medical weight loss. If you qualify, the science is settled: real, sustained loss plus a cardiovascular benefit that few weight interventions can claim. We grade the molecule here and hand off the shopping. For provider comparison, telehealth options, and where to actually get semaglutide, go to glp1picks.com, our sister site built specifically for that.
See the evidence →Evidence scope: Grade A: FDA-approved (2010) on multiple pivotal Phase 3 RCTs (rule 1 fired: FDA-approved for ≥1 indication). The only currently-marketed FDA-approved GHRH analog.
Sources: Drugs@FDA: Egrifta (tesamorelin) approval record · WADA Prohibited List (S2, GHRH analog) · Falutz et al., N Engl J Med 2007: tesamorelin pivotal Phase 3 (n=412)
A GHRH analog that stimulates the pituitary to release growth hormone, which reduces visceral (abdominal) fat.
Tesamorelin is an FDA-approved drug (Egrifta, 2010): Grade A, the strongest evidence tier here. But it is approved for HIV-associated visceral fat, not general weight loss; for that, approved GLP-1s are the evidence-backed route.
See the evidence →Evidence scope: FDA-approved for chronic weight management and type 2 diabetes, supported by the SURMOUNT and SURPASS phase 3 programs. SURMOUNT-1 showed mean body-weight reductions of 15.0, 19.5, and 20.9 percent across the 5, 10, and 15 mg doses at 72 weeks versus 3.1 percent on placebo. SURPASS-2 showed it was superior to semaglutide 1 mg on both HbA1c and weight. Unambiguous grade A.
Sources: SURMOUNT-1: Tirzepatide Once Weekly for the Treatment of Obesity (NEJM 2022, PMID 35658024) · SURPASS-2: Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (NEJM 2021, PMID 34170647)
A single peptide that activates two incretin receptors at once: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The dual agonism appears to produce greater appetite suppression and metabolic effect than GLP-1 alone, which is the leading explanation for its edge over semaglutide on weight and HbA1c.
Grade A, and on raw efficacy it is the strongest weight-loss drug approved to date, beating semaglutide head to head. If you are choosing between the two, that is a clinical and access conversation, not a science one. We grade the molecule here and hand off the shopping. For provider comparison and where to get tirzepatide, go to glp1picks.com, our sister site built for exactly that.
See the evidence →| Peptide | Overall grade | Legal & safety | Typical cost | Verdict | |
|---|---|---|---|---|---|
| AOD-9604 A modified fragment of human growth hormone that was supposed to melt fat without the side effects. It got a real Phase 2b obesity trial in humans and flat-out failed to beat placebo, which is why no regulator has ever approved it. | Grade F | See evidenceSee the evidence for AOD-9604 | |||
| Cagrilintide An investigational once-weekly amylin analog that produced about 11 percent weight loss on its own in phase 2 and is the partner half of the CagriSema combination, not an approved standalone drug. | Grade B | See evidenceSee the evidence for Cagrilintide | |||
| Dulaglutide A once-weekly GLP-1 approved for type 2 diabetes with a proven cardiovascular benefit, but never FDA-approved for obesity, so weight loss is a real but secondary effect. | Grade A | See evidenceSee the evidence for Dulaglutide | |||
| Liraglutide The original daily GLP-1 for weight and diabetes: less powerful than the weekly agents that followed, but FDA-approved, decades-proven, and with a documented cardiovascular benefit. | Grade A | See evidenceSee the evidence for Liraglutide | |||
| MOTS-c An "exercise-mimetic" metabolic peptide. Real mechanistic interest, but human evidence is association-only. | Grade D | See evidenceSee the evidence for MOTS-c | |||
| Retatrutide The next-generation weight-loss peptide with the strongest efficacy signal. But it is investigational and not yet available by any legal route. | Grade B | See evidenceSee the evidence for Retatrutide | |||
| Semaglutide The once-weekly GLP-1 that turned obesity into a treatable condition, with roughly 15 percent average body-weight loss in its landmark trial and a proven cardiovascular benefit on top. | Grade A | See evidenceSee the evidence for Semaglutide | |||
| Tesamorelin An FDA-approved peptide drug, not a research chemical. Proven to cut visceral fat, but approved for a narrow HIV indication. | Grade A | See evidenceSee the evidence for Tesamorelin | |||
| Tirzepatide The dual-hormone agonist that beat semaglutide head to head and delivered up to roughly 21 percent body-weight loss in its pivotal obesity trial, the most weight loss of any approved medication to date. | Grade A | See evidenceSee the evidence for Tirzepatide |
Reading this table: Grades refer to each compound's stated evidence scope, not every use in this category. Legal status and Safety are separate badges; Verdict is the compound summary. Affiliate availability never changes a grade. Full methodology.
FAQ
The FDA-approved GLP-1 medications, semaglutide and tirzepatide (Grade A), are the best-evidenced option, and we route you to a provider comparison for them. Tesamorelin (Grade A) is approved only for HIV-associated visceral fat. Retatrutide (Grade B) is investigational. MOTS-c is Grade D: animal data only.
MOTS-c improves metabolism and insulin sensitivity in animal models and gets marketed as an "exercise mimetic," but the human evidence is association-only, which puts it at Grade D. No controlled human trial shows it produces weight loss.
Yes. The GLP-1 medications semaglutide (Wegovy) and tirzepatide (Zepbound) are FDA-approved for weight loss and are the evidence-backed answer. Tesamorelin is FDA-approved but only for HIV-associated visceral fat, not general weight loss. Retatrutide (Grade B) is still investigational.
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