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The best peptides for fat loss, ranked on evidence

Six compounds that have actually been studied for body composition, in the order the human evidence supports. Two are approved drugs with large trials behind them. The rest are research compounds, and we say exactly how thin the data is for each.

By Lindy Health editorial Updated 18 Oct 2026
How we ranked these Ordered by evidence level first, then magnitude of effect in the best available trial. Compounds with no human data cannot rank above compounds with it, regardless of how popular they are. Full criteria in our methodology.

Quick answer

#CompoundClassEvidenceReported rangeStatus
1 Tirzepatide GLP-1 & incretins Regulator approved 2.5-15 mg Prescription
2 Semaglutide GLP-1 & incretins Regulator approved 250 mcg - 2.4 mg Prescription
3 Tesamorelin GHRH analogs Regulator approved 1-2 mg Prescription
4 Retatrutide GLP-1 & incretins Clinical trials 1-12 mg Research only
5 MOTS-c Mitochondrial & longevity Preliminary human 5-10 mg Research only
6 AOD-9604 Fat loss Clinical trials 300-600 mcg Research only

The ranking

01

Tirzepatide

Regulator approved GLP-1 & incretins

The most effective pharmacological weight-loss agent with an approval. Dual GIP/GLP-1 agonism produced greater loss than semaglutide in the only direct head-to-head, SURMOUNT-5. It is a prescription drug and the correct route to it is a licensed prescriber, not a vendor.

Evidence~60 human studies
Reported range2.5-15 mg
Half-life~5 days
Banned in sportNo
Full Tirzepatide record → Find a prescriber
TTirzepatide
02

Semaglutide

Regulator approved GLP-1 & incretins

The compound that reset expectations for the category. STEP trials put mean loss near 15% at 68 weeks. It ranks second only because tirzepatide beat it directly. Compounded supply is now restricted following the end of the FDA shortage listing.

Evidence~90 human studies
Reported range250 mcg - 2.4 mg
Half-life~7 days
Banned in sportNo
Full Semaglutide record → Find a prescriber
SSemaglutide
03

Tesamorelin

Regulator approved GHRH analogs

Approved, but for a narrow indication: visceral fat in HIV lipodystrophy. It reliably reduces visceral adipose tissue in that population. Extrapolating to general fat loss is a stretch the trials do not support.

Evidence~15 human studies
Reported range1-2 mg
Half-life~26-38 minutes
Banned in sportYes
Full Tesamorelin record → Find a prescriber
TTesamorelin
04

Retatrutide

Clinical trials GLP-1 & incretins Research use only

Phase II reported roughly 24% body weight reduction at 48 weeks, the largest figure in the class. It is investigational, not available by prescription, and material sold online is unregulated.

Evidence~8 human studies
Reported range1-12 mg
Half-life~6 days
Banned in sportNo
Full Retatrutide record →
RRetatrutide
05

MOTS-c

Preliminary human Mitochondrial & longevity Research use only

A mitochondria-encoded exercise mimetic acting through AMPK. The mechanism is sound and endogenous levels fall with age, but the human data is three small studies. It sits here on biological plausibility, not on outcome trials.

Evidence~3 human studies
Reported range5-10 mg
Half-life~1-2 hours
Banned in sportNo
Full MOTS-c record →

Material for this compound is sold for laboratory research only. It is not manufactured, tested or labelled for human administration.

MMOTS-c
06

AOD-9604

Clinical trials Fat loss Research use only

Included because it is sold everywhere as a fat-loss peptide, and ranked last because it failed its own phase IIb obesity trial against placebo. The preclinical story was good. The human result was not.

Evidence~6 human studies
Reported range300-600 mcg
Half-life~30 minutes
Banned in sportYes
Full AOD-9604 record →

Material for this compound is sold for laboratory research only. It is not manufactured, tested or labelled for human administration.

AAOD-9604

What we left out, and why

HGH Fragment 176-191
Its best-studied derivative, AOD-9604, failed its obesity trial. There is no reason to expect the parent fragment to do better.
Adipotide
Caused renal toxicity in primates. Development halted. Not a fat-loss option at any risk tolerance.
5-Amino-1MQ
Rodent data only, and not a peptide. Documented in the directory, excluded from a ranking.

Head-to-head comparisons

Semaglutide vs TirzepatideRetatrutide vs TirzepatideRetatrutide vs SemaglutideAOD-9604 vs SemaglutideSemaglutide vs TesamorelinAOD-9604 vs TesamorelinLiraglutide vs TirzepatideLiraglutide vs Semaglutide

References for the compounds in this guide

  1. Jastreboff AM, le Roux CW, Stefanski A, et al.. Tirzepatide for Obesity Treatment and Diabetes Prevention.N Engl J Med 2025.PubMed 39536238 · doi:10.1056/NEJMoa2410819
  2. Jastreboff AM, Aronne LJ, Ahmad NN, et al.. Tirzepatide Once Weekly for the Treatment of Obesity.N Engl J Med 2022.PubMed 35658024 · doi:10.1056/NEJMoa2206038
  3. Aronne LJ, Sattar N, Horn DB, et al.. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.JAMA 2024.PubMed 38078870 · doi:10.1001/jama.2023.24945
  4. Malhotra A, Grunstein RR, Fietze I, et al.. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.N Engl J Med 2024.PubMed 38912654 · doi:10.1056/NEJMoa2404881
  5. Packer M, Zile MR, Kramer CM, et al.. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.N Engl J Med 2025.PubMed 39555826 · doi:10.1056/NEJMoa2410027
  6. Aronne LJ, Horn DB, le Roux CW, et al.. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.N Engl J Med 2025.PubMed 40353578 · doi:10.1056/NEJMoa2416394
  7. Look M, Dunn JP, Kushner RF, et al.. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight.Diabetes Obes Metab 2025.PubMed 39996356 · doi:10.1111/dom.16275
  8. Frías JP, Davies MJ, Rosenstock J, et al.. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.N Engl J Med 2021.PubMed 34170647 · doi:10.1056/NEJMoa2107519
  9. Wilding JPH, Batterham RL, Davies M, et al.. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.Diabetes Obes Metab 2022.PubMed 35441470 · doi:10.1111/dom.14725
  10. Rubino DM, Greenway FL, Khalid U, et al.. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.JAMA 2022.PubMed 35015037 · doi:10.1001/jama.2021.23619
  11. Wilding JPH, Batterham RL, Calanna S, et al.. Once-Weekly Semaglutide in Adults with Overweight or Obesity.N Engl J Med 2021.PubMed 33567185 · doi:10.1056/NEJMoa2032183
  12. Rubino D, Abrahamsson N, Davies M, et al.. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.JAMA 2021.PubMed 33755728 · doi:10.1001/jama.2021.3224
  13. Wharton S, Freitas P, Hjelmesæth J, et al.. Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial.Lancet Diabetes Endocrinol 2025.PubMed 40961952 · doi:10.1016/S2213-8587(25)00226-8
  14. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al.. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes.N Engl J Med 2023.PubMed 37952131 · doi:10.1056/NEJMoa2307563
  15. Rahman OF, Lee SJ, Seeds WA. Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions.J Am Acad Orthop Surg Glob Res Rev 2026.PubMed 41490200 · doi:10.5435/JAAOSGlobal-D-25-00236
  16. Mayfield CK, Bolia IK, Feingold CL, et al.. Injectable Peptide Therapy: A Primer for Orthopaedic and Sports Medicine Physicians.Am J Sports Med 2026.PubMed 41476424 · doi:10.1177/03635465251357593
  17. Badran AS, Helal A, Shata KS, et al.. Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: A meta-analysis of randomized controlled trials.Obes Res Clin Pract 2026.PubMed 41545261 · doi:10.1016/j.orcp.2026.01.002
  18. Mendias CL, Awan TM. Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance.Sports Med 2026.PubMed 41966639 · doi:10.1007/s40279-026-02437-0
  19. Dhillon S. Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy.Drugs 2011.PubMed 21668043 · doi:10.2165/11202240-000000000-00000
  20. Spooner LM, Olin JL. Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy.Ann Pharmacother 2012.PubMed 22298602 · doi:10.1345/aph.1Q629
  21. Renke G, Chinellato L. Therapeutic Peptides in Aesthetic, Metabolic and Endocrine Conditions: Effects, Safety, Clinical Applications, and Future Perspectives.Int J Mol Sci 2026.PubMed 42123471 · doi:10.3390/ijms27093890
  22. Corley MJ, Letendre SL, Nightingale S. CROI 2024: Neuropsychiatric Complications in People With HIV.Top Antivir Med 2024.PubMed 39746672
  23. Jastreboff AM, Kaplan LM, Frías JP, et al.. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.N Engl J Med 2023.PubMed 37366315 · doi:10.1056/NEJMoa2301972
  24. Sanyal AJ, Kaplan LM, Frias JP, et al.. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.Nat Med 2024.PubMed 38858523 · doi:10.1038/s41591-024-03018-2

Literature retrieved from PubMed on October 16, 2026, favouring human studies and reviews. Numbered markers in the text show which paper supports which statement; uncited entries are background reading.

Read this first This page ranks published reference data. It is not medical advice and not a recommendation to use any compound. Several compounds documented on this site are not approved for human use.