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Weight-Loss Peptide Time-Course Review

Trial reports and related reading

The full source list follows these starting points. The study titles identify their subjects more precisely than a single weight-loss headline can.

Direct comparisons and weight trials

Start with the 72-week tirzepatide–semaglutide obesity comparison. Then the 40-week diabetes comparison shows how a different population and treatment comparison change the question.

For separate obesity trials, read the retatrutide Phase 2 report, semaglutide STEP 1 and tirzepatide SURMOUNT-1 alongside their actual follow-up periods. I favour reading the population and methods before trying to reconcile the percentages.

Health outcomes and tolerability

The SELECT cardiovascular-outcomes report and FLOW kidney-outcomes report move beyond the weight question. For tolerability, the semaglutide safety review and tirzepatide pancreatitis and biliary-disease meta-analysis examine different kinds of risk. The tirzepatide clinical reference chapter provides background on the medicine.

Retatrutide across measurements

The early retatrutide study, type 2 diabetes trial, liver-fat substudy and later lipid and metabolite analysis cover distinct measurements. The receptor-structure paper is laboratory work, and the development review brings the programme together.

AOD-9604 in animals and people

The mouse receptor experiment and mouse fat-oxidation experiment explain the original metabolic interest. Compare them with the human safety programme and metabolism and non-clinical safety account. The rabbit osteoarthritis experiment asks a separate question about cartilage.

  1. Katsi V, Koutsopoulos G, Fragoulis C, Dimitriadis K, Tsioufis K. Retatrutide-A Game Changer in Obesity Pharmacotherapy. Biomolecules. 2025;15:796. ↗
  2. Li W, Zhou Q, Cong Z, Yuan Q, Li W, Zhao F, Xu HE, Zhao LH, Yang D, Wang MW. Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide. Cell Discovery. 2024;10:77. ↗
  3. Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, Harris C, Schloot NC, Du Y, Mather KJ, Haupt A, Hartman ML. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine. 2024;30:2037-2048. ↗
  4. Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. ↗
  5. Rosenstock J, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial. Lancet. 2023;402(10401):529-544. ↗
  6. Urva S, Coskun T, Loh MT, Du Y, Thomas MK, Gurbuz S, Haupt A, Benson CT, Hernandez-Illas M, D'Alessio DA, Milicevic Z. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet. 2022;400:1869-1881. ↗
  7. Pearson MJ, et al. Retatrutide And Lipid And Metabolite Profiles In Participants With Obesity With Or Without Type 2 Diabetes. The Journal of clinical endocrinology and metabolism. 2026. ↗
  8. Aronne LJ, et al. (SURMOUNT-5 Investigators). Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025. ↗
  9. Perkovic V, et al. (FLOW Trial Committees and Investigators). Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024. ↗
  10. Lincoff AM, et al. (SELECT Trial Investigators). Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023. ↗
  11. Wilding JPH, et al. (STEP 1 Study Group). Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021. ↗
  12. Smits MM, Van Raalte DH. Safety of Semaglutide. Front Endocrinol (Lausanne). 2021. ↗
  13. Farzam K, Patel P. Tirzepatide (StatPearls). StatPearls [Internet], NCBI Bookshelf. 2024. ↗
  14. Zeng Q, et al. Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023. ↗
  15. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022. ↗
  16. Frias JP, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021. ↗
  17. Kwon DR, Park GY. Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Annals of Clinical and Laboratory Science. 2015;45(4):426-432. ↗
  18. More MI, Kenley D. Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health. Journal of Endocrinology and Metabolism. 2014;4(3):64-77. ↗
  19. Stier H, Vos E, Kenley D. Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Journal of Endocrinology and Metabolism. 2013;3(1-2):7-15. ↗
  20. Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001;142(12):5182-5189. ↗
  21. Heffernan MA, Thorburn AW, Fam B, Summers R, Conway-Campbell B, Waters MJ, Ng FM. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. International Journal of Obesity and Related Metabolic Disorders. 2001;25(10):1442-1449. ↗