# Growth hormone secretagogues Rating: Early — Mostly animal or cell studies; few or uncontrolled human data Type: Guide Updated: 2026-11-01 Canonical: https://heretic.bio/articles/growth-hormone-secretagogues-tesamorelin-cjc-1295-ipamorelin-mk-677.html > Growth hormone secretagogues make the body release more of its own growth hormone. Only tesamorelin is FDA-approved, for excess belly fat in people with HIV, where five randomized trials show less visceral and liver fat and slightly more lean mass. CJC-1295 has only short pharmacology studies, ipamorelin's one human efficacy trial (bowel surgery recovery) failed, and oral MK-677 (ibutamoren) added about 1.6 kg of lean mass over a year in healthy older adults without improving strength or function, while raising fasting glucose. The popular CJC-1295 plus ipamorelin stack has never been tested in a trial. > "CJC-1295 / ipamorelin" is a clinic product category, not an evidence category. The only growth-hormone-releasing hormone analogue with an FDA approval and a 2026 meta-analysis of randomized trials is tesamorelin, and that evidence is in HIV-associated lipodystrophy and fatty liver, not in healthy aging. In 65 healthy older adults, ibutamoren (MK-677) increased fat-free mass and fasting glucose without showing a strength or function gain. The trial was too small and short to settle functional outcomes. Ipamorelin's selectivity story is from animals. Its one registered human efficacy trial did not meet the primary endpoint. This page grades a drug class that clinics sell as an anti-aging package. For where the unapproved members stand legally, see [the 2026 FDA peptide reclassification](fda-peptide-reclassification-2026.html); for how we grade peptide evidence, [the peptide evidence framework](peptide-evidence-grading-framework.html); for product quality, [peptide sources and quality](peptide-sources-and-quality.html). Other drugs that change body composition, with different evidence, are covered under [GLP-1 drugs](glp-1-peptides-semaglutide-tirzepatide-retatrutide.html) and [hormone optimization](hormone-optimization-trt-hrt-perimenopause.html). None of these replaces [training](exercise-science-and-longevity.html). Not medical advice. Raising IGF-1 on purpose carries a theoretical cancer concern that none of these trials was large or long enough to test. ## Four compounds, four evidence classes Compound | What it is | Best human evidence | What that evidence is not ---|---|---|--- Tesamorelin | Synthetic GHRH analogue; FDA-approved (Egrifta) for excess abdominal fat in HIV lipodystrophy | 5-RCT meta-analysis through July 2025; one NAFLD RCT | A healthy-aging or longevity trial CJC-1295 | Long-acting GHRH analogue (drug-affinity complex) | Two short randomized PK/PD studies in healthy adults, 2006 | A body-composition or clinical-outcome trial Ipamorelin | Pentapeptide ghrelin-receptor agonist | Phase 2 postoperative-ileus RCT, primary endpoint missed | A human fat-loss or muscle trial Ibutamoren (MK-677) | Oral non-peptide ghrelin mimetic | 1-year RCT in healthy adults 60–81 years | A strength, function, or visceral-fat drug The compounded "CJC + ipamorelin" stack has never been tested as a combination in a published trial. ## Tesamorelin: the only approved member ### Approval boundary The 12 November 2010 FDA approval announcement described tesamorelin acetate injection (Egrifta; Theratechnologies, then marketed by EMD Serono) as the first treatment indicated to reduce excess abdominal fat in HIV-infected patients with lipodystrophy. The same announcement said safety and efficacy had not been established in children or in renal or hepatic impairment, that discontinuation should be considered in critically ill patients, and that approval was conditioned on a diabetic-retinopathy trial and a long-term observational safety study. A 2024 re-analysis states the current factual boundary in one sentence: tesamorelin is the only FDA-approved therapy for abdominal fat accumulation in people with HIV, and the phase 3 trials predated integrase-inhibitor regimens ([PMID 38905488](https://pubmed.ncbi.nlm.nih.gov/38905488/)). ### 2026 meta-analysis of the HIV trials Badran et al., _Obesity Research & Clinical Practice_ 2026;20(1):2–12 ([PMID 41545261](https://pubmed.ncbi.nlm.nih.gov/41545261/)). Systematic search of PubMed, Embase, Scopus, Web of Science, and CENTRAL through July 2025. Randomized trials of tesamorelin versus placebo in adults with HIV. Five RCTs. Random-effects meta-analysis. Risk of bias with RoB 2.0. Certainty with GRADE. Outcome | Mean difference (95% CI) | P ---|---|--- Visceral adipose tissue | −27.71 cm² (−38.37 to −17.06) | <0.001 Trunk fat | −1.18 kg (−1.40 to −0.96) | <0.001 Limb fat | −0.22 kg (−0.35 to −0.08) | 0.001 Hepatic fat | −4.28% (−6.31 to −2.24) | <0.001 Waist circumference | −1.61 cm (−2.28 to −0.95) | <0.001 Lean body mass | +1.42 kg (1.13 to 1.71) | <0.001 Subcutaneous adipose tissue | no significant reduction | — BMI | no significant reduction | — CD4+ T-cell count | no significant change | — Adverse events associated with tesamorelin in that pool included arthralgia, myalgia, paresthesia, and injection-site erythema. Read the limb-fat row. Tesamorelin is not a selective "visceral only" cosmetic. Limb fat also fell, by a smaller amount. Lean mass rose. BMI did not move. That pattern is visceral and hepatic fat down, lean mass up, scale weight roughly unchanged — in HIV, not in a gym cohort. ### Liver fat in HIV: the single dedicated RCT Stanley et al., _Lancet HIV_ 2019 ([PMID 31611038](https://pubmed.ncbi.nlm.nih.gov/31611038/); [NCT02196831](https://clinicaltrials.gov/study/NCT02196831)). Randomized, double-blind, multicenter, identical placebo. People with HIV and hepatic fat fraction ≥5% by proton magnetic resonance spectroscopy. Tesamorelin 2 mg once daily versus placebo for 12 months, then 6 months open-label tesamorelin for all. Primary endpoint: change in hepatic fat fraction. Primary safety endpoint: glucose. Intention-to-treat. * 61 patients enrolled (20 August 2015 to 16 January 2019). Abstract assignment counts: 30 tesamorelin, 30 placebo. * Absolute effect on hepatic fat fraction: −4.1% (95% CI −7.6 to −0.7), P=0.018. Relative reduction from baseline −37% (95% CI −67 to −7), P=0.016. * Hepatic fat fraction <5% at 12 months: 35% versus 4%, P=0.0069. * Fasting glucose and glycated hemoglobin: not different between groups at 12 months. * More localized injection-site complaints with tesamorelin; none judged serious. * The paper's own limit: further studies are needed for long-term effects on liver histology. The imaging result is not a histology result. ### Integrase-inhibitor era: same trial, smaller slice The 2024 paper is a secondary analysis of that same 61-person trial ([PMID 38905488](https://pubmed.ncbi.nlm.nih.gov/38905488/)). Among 38 participants on an integrase-inhibitor regimen at baseline, 15 on tesamorelin and 16 on placebo completed 12 months. * Visceral fat, median (IQR): −25 cm² (−93 to −2) versus +14 cm² (3 to 41), P=0.001. * Hepatic fat: −4.2% (−12.3 to −2.7) versus −0.5% (−3.9 to 2.7), P=0.01. * Trunk-to-appendicular fat ratio: −0.1 (−0.3 to 0.0) versus 0.0 (−0.1 to 0.1), P=0.03. * Adverse-event frequency, including hyperglycemia, was similar between groups. This is the first dedicated look at tesamorelin on modern HIV regimens. It is a completer analysis inside an already small trial (15 versus 16). It does not license use outside HIV. ### Incentive note The 2024 paper's conflict statement: one author consults for Theratechnologies (the tesamorelin company) and another is an inventor on a patent for GHRH or analogues for hepatic disease. The original liver-fat trial received NIH funding. The consulting relationship and hepatic-use patent are commercial interests worth tracking. The trial tested people with HIV; benefit in NAFLD without HIV remains an open question. ## CJC-1295: pharmacokinetics, not outcomes Teichman et al., _Journal of Clinical Endocrinology & Metabolism_ 2006 ([PMID 16352683](https://pubmed.ncbi.nlm.nih.gov/16352683/)). Two randomized, placebo-controlled, double-blind, ascending-dose trials, 28 and 49 days, in healthy adults aged 21–61 years. Subcutaneous CJC-1295 or placebo. Four ascending single doses in the first study; two or three weekly or biweekly doses in the second. * After one injection, mean plasma growth hormone rose 2- to 10-fold for 6 days or more, dose-dependently. * Mean IGF-I rose 1.5- to 3-fold for 9–11 days. * Estimated half-life 5.8–8.1 days. * After repeated doses, mean IGF-I stayed above baseline for up to 28 days. The authors noted a cumulative effect. * No serious adverse reactions reported. They described it as safe and relatively well tolerated, particularly at 30 or 60 µg/kg. That is a pharmacology paper. It does not report fat mass, lean mass, strength, glucose as a prespecified efficacy outcome, or any clinical event. A multi-day IGF-I elevation is the opposite of the "preserves physiologic pulses, so it is safer than growth hormone" claim attached to short-acting secretagogues. CJC-1295 was built to last. As of October 2026, PubMed lists no randomized trial of CJC-1295 with body-composition or healthy-aging outcomes. ## Ipamorelin: selective in swine, unproven in humans ### Animal selectivity (1998) [PMID 9849822](https://pubmed.ncbi.nlm.nih.gov/9849822/), _European Journal of Endocrinology_. Ipamorelin is a pentapeptide, Aib-His-D-2-Nal-D-Phe-Lys-NH2, identified from a series that dropped the central Ala-Trp of GHRP-1. * Rat pituitary cells: GH release potency and efficacy similar to GHRP-6 (EC50 1.3±0.4 nmol/L, Emax 85±5%, versus 2.2±0.3 nmol/L and 100%). Antagonist profiling pointed to a GHRP-like receptor, not the GHRH receptor. * FSH, LH, prolactin, and TSH were not affected by the secretagogues tested in that swine experiment. This is the paper behind "ipamorelin is the clean one." It is rat and swine pharmacology. It is not a human safety trial. ### The human efficacy trial that exists [PMID 25331030](https://pubmed.ncbi.nlm.nih.gov/25331030/), _International Journal of Colorectal Disease_ 2014\. Phase 2, multicenter, double-blind, placebo-controlled proof-of-concept trial of intravenous ipamorelin for postoperative ileus after bowel resection. [NCT00672074](https://clinicaltrials.gov/study/NCT00672074). Adults, open or laparoscopic small- or large-bowel resection. Ipamorelin 0.03 mg/kg versus placebo, twice daily, from postoperative day 1 through day 7 or discharge. * 117 enrolled; 114 in the safety and modified intention-to-treat populations. * Any treatment-emergent adverse event: 87.5% ipamorelin versus 94.8% placebo. * Primary efficacy endpoint, time from first dose to tolerance of a standardized solid meal: median 25.3 versus 32.6 hours, P=0.15. * No significant differences on key or secondary efficacy analyses. Well tolerated in that short postoperative window. Not effective for the indication that was actually tested. As of October 2026 there is no human body-composition trial of ipamorelin; the rest of its clinical-sounding literature is the 1998 pharmacology paper, doping-detection papers and animal work, such as a 2024 ferret study of cisplatin-induced weight loss ([PMID 39043357](https://pubmed.ncbi.nlm.nih.gov/39043357/)) and a 2024 fish reproduction study ([PMID 38996787](https://pubmed.ncbi.nlm.nih.gov/38996787/)). ### Anti-doping, not a clinical endorsement A 2015 urine method paper gave GHRP-1, GHRP-2, GHRP-6, hexarelin, and ipamorelin intranasally to one volunteer each and tracked metabolites ([PMID 25869809](https://pubmed.ncbi.nlm.nih.gov/25869809/)). Those peptides were treated as prohibited growth-hormone releasing peptides. Ipamorelin was extensively metabolized; the (1–4) free acid remained after the parent was gone. That paper is about detection windows. Sporting authorities already classed ipamorelin with the other GHRPs in 2015, and the WADA Prohibited List bans growth-hormone-releasing factors, including GHRH analogues and GH secretagogues, at all times (section S2). ## Ibutamoren (MK-677): the trial clinics do not quote Nass et al., _Annals of Internal Medicine_ 2008 ([PMID 18981485](https://pubmed.ncbi.nlm.nih.gov/18981485/)). Two-year, double-blind, randomized, placebo-controlled, modified-crossover trial at a university general clinical research center. 65 healthy adults aged 60–81 (men, women on hormone replacement, women not on hormone replacement). MK-677 25 mg or placebo once daily by mouth. Primary endpoints at 1 year: fat-free mass and abdominal visceral fat. What moved: * Growth hormone and IGF-I rose into the range of healthy young adults. No serious adverse effects in the authors' summary. * Fat-free mass: placebo −0.5 kg (95% CI −1.1 to 0.2) versus MK-677 +1.1 kg (0.7 to 1.5), P<0.001. * Body cell mass (intracellular water): −1.0 kg (−2.1 to 0.2) versus +0.8 kg (−0.1 to 1.6), P=0.021. * Body weight: +0.8 kg (−0.3 to 1.8) versus +2.7 kg (2.0 to 3.5), P=0.003. * Limb fat: +0.24 kg versus +1.1 kg, P=0.001. * Fasting glucose: +0.3 mmol/L (5 mg/dL) on MK-677, P=0.015. Insulin sensitivity decreased. * Cortisol: +47 nmol/L (95% CI 28 to 71) on MK-677, P=0.020. * LDL cholesterol fell versus baseline on MK-677 (−0.14 mmol/L, 95% CI −0.27 to −0.01, P=0.026). No between-group difference in total or HDL cholesterol. * Bone mineral density changes were consistent with increased remodeling. * Most frequent side effects: increased appetite that subsided over a few months; transient mild lower-extremity edema; muscle pain. * Two-year exploratory analyses confirmed the one-year results. What did not move: * Abdominal visceral fat: no significant difference. * Total fat mass: no significant difference. * Strength and function: the fat-free-mass increase did not produce changes in strength or function. * The authors' limitation: duration and sample size were insufficient to evaluate functional endpoints in healthy elderly people. Their conclusion asked for long-term functional studies. Those studies are not the basis of current gray-market use. MK-677 is not a peptide. It is grouped here because clinics sell it beside ipamorelin and because it hits the same ghrelin receptor. It is the compound on this page with the most relevant human experiment for the "replace growth hormone in aging" pitch, and that experiment's functional endpoint was null while glucose got worse. ## Claims audit Marketing claim | Verdict ---|--- "CJC/ipa is the physiologic alternative to growth hormone" | CJC-1295 raises IGF-I for days to weeks after injection ([PMID 16352683](https://pubmed.ncbi.nlm.nih.gov/16352683/)). That is sustained stimulation, not a sleep-pulse replica. No combination trial. "Ipamorelin does not raise cortisol, so it is safer" | Shown in swine at pharmacologic doses ([PMID 9849822](https://pubmed.ncbi.nlm.nih.gov/9849822/)). Not shown as a clinical-safety advantage in a human outcomes trial. "Secretagogues build muscle and strip visceral fat in healthy adults" | Ibutamoren increased fat-free mass and did not reduce visceral fat, and did not improve strength ([PMID 18981485](https://pubmed.ncbi.nlm.nih.gov/18981485/)). Tesamorelin reduces visceral fat in HIV ([PMID 41545261](https://pubmed.ncbi.nlm.nih.gov/41545261/)). Different drugs, different populations. "Tesamorelin is a NAFLD drug for anyone" | One HIV trial, imaging not histology, inventor patent on the hepatic use ([PMID 31611038](https://pubmed.ncbi.nlm.nih.gov/31611038/), [PMID 38905488](https://pubmed.ncbi.nlm.nih.gov/38905488/)). "The stack is FDA-approved" | Tesamorelin is approved for a narrow HIV indication. CJC-1295 and ipamorelin are not. "No metabolic downside" | Ibutamoren raised fasting glucose and lowered insulin sensitivity. Tesamorelin's HIV trials did not show a glucose or HbA1c difference at 12 months. Do not average those. ## Practical context The doses the trials used are listed under "What studies and practitioners report". The schedules sold online are not what was studied: * CJC-1295 has a half-life of about 6 to 8 days ([PMID 16352683](https://pubmed.ncbi.nlm.nih.gov/16352683/)), so frequent clinic schedules are not the pharmacology that was studied. * Ipamorelin's only human efficacy trial gave it intravenously for a week after surgery ([PMID 25331030](https://pubmed.ncbi.nlm.nih.gov/25331030/)). That is not the long-term injection use sold online, and it did not work for ileus. Monitoring that the trials themselves treated as relevant: IGF-1, fasting glucose, HbA1c, injection-site reactions, edema, arthralgia, paresthesia. The 2010 tesamorelin approval was conditioned on a diabetic-retinopathy study, whose result has not been published. Quality and gray-market risk for anything that is not the approved tesamorelin product: [Peptide Sources and Quality](peptide-sources-and-quality.html). ## What to watch * A human body-composition RCT of ipamorelin, or of CJC-1295 plus ipamorelin, would change this picture. None has been published as of October 2026. * Tesamorelin outside HIV (obesity without HIV, MASLD without HIV, healthy aging) is an evidence gap, not a quiet extension of the HIV results. The patent on hepatic use is a reason to demand an independent trial. * Ibutamoren's null functional result at one year, with worse glucose, is the prior that any new oral ghrelin mimetic has to beat. Do not let a newer brand name reset that prior. * Neoplasia and long-term IGF-1 elevation are not answered by 28-day PK studies or by 12-month HIV fat trials. ## Who paid, and how it got here ### How it got here - FDA still lists ibutamoren in Category 2 under both 503A and 503B, and ipamorelin acetate under 503B. CJC-1295 and the 503A ipamorelin nomination were withdrawn and removed from Category 2 on 22 April 2026; this did not create a 503A compounding pathway. ([FDA compounding lists](https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks)) - The 30 October 2026 HHS draft interim enforcement policy covers six specified peptides. CJC-1295, ipamorelin and ibutamoren are outside its scope. ([HHS Federal Register notice](https://www.govinfo.gov/content/pkg/FR-2026-10-30/html/2026-22192.htm); [HHS policy text](https://www.hhs.gov/sites/default/files/hhs-503a-peptide-enforcement-discretion-policy-appendix-b.pdf)) - The 2026 WADA list prohibits tesamorelin, CJC-1295, ipamorelin and ibutamoren at all times under S2. ([WADA 2026 list](https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf)) ### Who paid for the key studies - Stanley 2019, placebo-controlled HIV liver-fat RCT, n=61: Liver fat fell; glucose measures did not differ between groups. Funding and interests: NIH/NIAID (public funding). ([PubMed funding record](https://pubmed.ncbi.nlm.nih.gov/31611038/)) - Fourman 2024, HIV RCT subgroup, n=38; 31 completers: Visceral and hepatic fat fell on integrase-inhibitor regimens. Funding and interests: NIH/NIDDK (public funding). ([PubMed funding record](https://pubmed.ncbi.nlm.nih.gov/38905488/)) - Fourman 2024, HIV RCT subgroup, n=38; author interests: Visceral and hepatic fat fell on integrase-inhibitor regimens. Funding and interests: Fourman consulted for Theratechnologies/Amryt; Stanley consulted for RosVivo and received Pfizer support; Grinspoon held a hepatic-use patent. ([Conflict-of-interest statement](https://pubmed.ncbi.nlm.nih.gov/38905488/)) - Nass 2008, placebo-controlled MK-677 RCT, n=65; funding: Fat-free mass increased; function unchanged; fasting glucose increased. Funding and interests: NIH (public funding); Deutsche Forschungsgemeinschaft supported Nass; Merck supplied drug and placebo. ([Paper's funding statement](https://pmc.ncbi.nlm.nih.gov/articles/PMC2757071/)) - Ipamorelin postoperative-ileus RCT, n=117 enrolled: Primary and secondary efficacy endpoints did not differ significantly. Funding and interests: Helsinn Therapeutics (U.S.), Inc (industry sponsor). ([Trial registry](https://clinicaltrials.gov/study/NCT00672074)) - Stanley 2019, placebo-controlled HIV liver-fat RCT, n=61; material support: Liver fat fell; glucose measures did not differ between groups. Funding and interests: Theratechnologies supplied study material. ([Paper's funding statement](https://pmc.ncbi.nlm.nih.gov/articles/PMC6981288/)) Checked 2026-11-01. ## Sources 1. Tesamorelin on integrase inhibitors, secondary analysis, 2024: PMID 38905488 (PubMed 38905488) 2. Tesamorelin meta-analysis, 5 RCTs, search through July 2025: PMID 41545261 (PubMed 41545261) 3. Tesamorelin NAFLD RCT, Lancet HIV 2019, NCT02196831 : PMID 31611038 (PubMed 31611038, NCT02196831) 4. CJC-1295 PK/PD, JCEM 2006: PMID 16352683 (PubMed 16352683) 5. Ipamorelin pharmacology, Eur J Endocrinol 1998: PMID 9849822 (PubMed 9849822) 6. Ipamorelin postoperative ileus phase 2, NCT00672074 : PMID 25331030 (PubMed 25331030, NCT00672074) 7. PubMed 39043357 (PubMed 39043357) 8. PubMed 38996787 (PubMed 38996787) 9. GHRP urine metabolites after nasal dosing, 2015: PMID 25869809 (PubMed 25869809) 10. Ibutamoren 1-year body composition, Ann Intern Med 2008: PMID 18981485 (PubMed 18981485)