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Peptide Empire

References

The reading list, from the sepsis trials to kidney outcomes and brain imaging.

Clinical outcomes and biological questions

The papers below concern five different research programmes. For semaglutide, STEP 1, SELECT and FLOW address weight, cardiovascular outcomes and a kidney-disease composite in their respective populations. The direct tirzepatide–semaglutide comparison adds a different weight-loss question.

In thymosin research, ETASS precedes the larger TESTS sepsis trial. Other papers concern immune biology, cancer treatment or a retrospective COVID-19 cohort. They answer questions at different levels.

The CJC-1295 papers include early human pharmacology, blood-protein changes and analytical identification of an unknown preparation. The NAD+ list includes trials of NMN and NR, alongside reviews of metabolism and human efficacy. For PT-141, RECONNECT, its open-label extension, the brain-imaging study and the prescribing information supply the clinical context; the hamster experiment concerns an animal model of reward.

The variety of questions becomes visible in the titles, even when a broad reputation starts to take over.

  1. Wu J, Pei F, Zhou L, et al. The efficacy and safety of thymosin alpha1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ. 2025. ↗
  2. Dominari A, Hathaway Iii D, Pandav K, et al. Thymosin alpha 1: A comprehensive review of the literature. World J Virol. 2020. ↗
  3. Liu Y, Pan Y, Hu Z, et al. Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells. Clin Infect Dis. 2020. ↗
  4. Costantini C, Bellet MM, Pariano M, et al. A Reappraisal of Thymosin Alpha1 in Cancer Therapy. Front Oncol. 2019. ↗
  5. Wu J, Zhou L, Liu J, et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013. ↗
  6. Romani L, Bistoni F, Montagnoli C, et al. Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance. Blood. 2006. ↗
  7. Goldstein AL, Low TL, McAdoo M, et al. Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proc Natl Acad Sci U S A. 1977. ↗
  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. Granata R, Leone S, Zhang X, Gesmundo I, et al. Growth hormone-releasing hormone and its analogues in health and disease. Nat Rev Endocrinol. 2025;21(3):180-195. ↗
  14. Henninge J, Pepaj M, Hullstein I, Hemmersbach P. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Drug Test Anal. 2010;2(11-12):647-650. ↗
  15. Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Horm IGF Res. 2009;19(6):471-477. ↗
  16. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805. ↗
  17. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-4797. ↗
  18. Vinten KT, Trętowicz MM, Coskun E, van Weeghel M, Cantó C, Zapata-Pérez R, Janssens GE, Houtkooper RH. NAD(+) precursor supplementation in human ageing: clinical evidence and challenges. Nat Metab. 2025;7:1974-1990. ↗
  19. Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience 2023. 2023;45:29-43. ↗
  20. Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372:1224-1229. ↗
  21. Covarrubias AJ, et al. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021. ↗
  22. Conze D, Brenner C, Kruger CL. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep. 2019;9:9772. ↗
  23. Borland JM, Kohut-Jackson AL, Peyla AC, Hall MA, Mermelstein PG, Meisel RL. Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder. Neuropharmacology. 2025;267:110299. ↗
  24. Thurston L, Hunjan T, Mills EG, Wall MB, Ertl N, Phylactou M, Muzi B, Patel B, Alexander EC, Suladze S, Modi M, Eng PC, Bassett PA, Abbara A, Goldmeier D, Comninos AN, Dhillo WS. Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder. J Clin Invest. 2022;132(19):e152341. ↗
  25. Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Simon JA. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019;134(5):899-908. ↗
  26. Simon JA, Kingsberg SA, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Clayton AH. Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder. Obstet Gynecol. 2019;134(5):909-917. ↗
  27. U.S. Food and Drug Administration / DailyMed. Bremelanotide Injection — US Prescribing Information (DailyMed/FDA). DailyMed (US FDA structured product label). 2019. ↗