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peptideradar

The peptideradar reading room

The source list includes clinical trials, observational work, experiments in animals and cells, and reviews of earlier findings.

Starting points

The MOTS-c study identifying CK2 as a molecular target starts the main argument here: responses in muscle and fat differed in mice. The KPV uptake paper investigates entry into intestinal cells, and the retatrutide receptor study examines interactions with several hormone receptors in laboratory systems.

For retatrutide's clinical responses, the obesity trial and type 2 diabetes trial provide controlled human results. The MOTS-c dialysis cohort instead studies a peptide already present in human blood. Those experiments are where I'd anchor a discussion of benefits before moving to broader claims.

The complete reading list follows, with the papers' published titles and identifiers.

  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. Kumagai H, Kim SJ, Miller B, et al. MOTS-c modulates skeletal muscle function by directly binding and activating CK2. iScience. 2024;27(11):111212. ↗
  9. Bolignano D, Greco M, Presta P, Duni A, et al. The Mitochondrial-Derived Peptide MOTS-c May Refine Mortality and Cardiovascular Risk Prediction in Chronic Hemodialysis Patients: A Multicenter Cohort Study. Blood Purification. 2024;53(10):824-837. ↗
  10. Wan W, Zhang L, Lin Y, Rao X, Wang X, Hua F, Ying J. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. Journal of Translational Medicine. 2023;21(1):36. ↗
  11. Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications. 2021;12(1):470. ↗
  12. Kim KH, Son JM, Benayoun BA, Lee C. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metabolism. 2018;28(3):516-524.e7. ↗
  13. Zhang D, et al. PepT1-targeted nanodrug based on co-assembly of anti-inflammatory peptide and immunosuppressant for combination treatment of acute and chronic DSS-induced colitis. Front Pharmacol. 2024;15:1442876. ↗
  14. Xiao B, Xu Z, Viennois E, et al. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Mol Ther. 2017;25(7):1628-1640. ↗
  15. Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, Yan Y, Sitaraman S, Merlin D. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166-178. ↗
  16. Kannengiesser K, Maaser C, Heidemann J, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008;14(3):324-331. ↗
  17. Brzoska T, Luger TA, Maaser C, Abels C, Bohm M. Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocr Rev. 2008;29(5):581-602. ↗