CJC-1295 WITH DAC (DAC:GRF)

CJC-1295 is a synthetic analogue of Growth Hormone–Releasing Hormone (GHRH). The DAC (Drug Affinity Complex) form corresponds to the 29–amino acid peptide known as Modified GRF (1–29), which lacks the C-terminal extension (N^ε-maleimidopropionyl lysine). It acts by binding to pituitary GHRH receptors, stimulating pulsatile secretion of endogenous GH in a manner analogous to natural GHRH. The main pharmacological difference is that CJC-1295 with DAC has a prolonged half-life (~6–8 days) due to bioconjugation with albumin, which extends its circulation time. In contrast, CJC-1295 without DAC has a short half-life (≈30 minutes) and produces transient increases in GH, more closely mimicking physiological pulses. Human studies with CJC-1295 (with DAC) show that a single subcutaneous injection can raise plasma GH levels 2- to 10-fold for at least 6 days and increase IGF-1 by 1.5- to 3-fold for 9–11 days—effects attributable to DAC technology. The non-DAC variant would require more frequent administrations to maintain elevated GH levels due to rapid clearance.
 
Known or Proposed Clinical/Therapeutic Uses
CJC-1295 (with DAC) was investigated for the treatment of HIV-associated visceral lipodystrophy (abdominal fat accumulation in patients on antiretroviral therapy) and in adults with GH deficiency. It reached phase II clinical trials, but development was halted after the unexpected death of a trial participant (likely attributable to a pre-existing cardiovascular event rather than the drug itself). Consequently, CJC-1295 did not receive medical approval. The non-DAC form (Mod-GRF 1–29) also has no approved uses; however, in experimental settings it is used in combination with other secretagogues (e.g., ipamorelin) to enhance GH release, leveraging complementary actions: non-DAC CJC-1295 provides a rapid but short stimulus, while ipamorelin acts on the ghrelin receptor to trigger immediate GH release, and the DAC version (when used) sustains prolonged elevated levels. Anti-aging applications, improvements in body composition (muscle gain, fat reduction), or use in conditions such as sarcopenia have also been proposed, but these lack robust clinical validation to date.
 
Side Effects or Associated Risks
Reported side effects of CJC-1295 are generally similar to those of chronic GH stimulation. They include local injection-site reactions (redness, pain, swelling) and, particularly with DAC CJC-1295, systemic vasodilatory effects such as facial flushing, warmth, and occasional transient hypotension after injection. Some users report mild dizziness or nausea immediately following administration. Sustained elevation of IGF-1 can lead to fluid retention with peripheral edema, as well as arthralgia and carpal tunnel–like symptoms (tingling or numbness of the hands), similar to effects seen with exogenous GH therapy. An important risk is immunogenicity. Additionally, because the GH/IGF-1 axis can stimulate cellular proliferation, these treatments should not be used in individuals with active cancer and are considered contraindicated in patients with a history of neoplasia or disorders of the hypothalamic–pituitary axis without strict medical supervision. In early clinical studies, DAC CJC-1295 was relatively well tolerated and no serious adverse events were observed in healthy volunteers, but careful monitoring is necessary for use outside of research protocols.