Tesamorelin + Ipamorelin Blend

Component Composition

This product is a fixed-composition vial containing tesamorelin and ipamorelin in defined ratios. Tesamorelin is a synthetic 44-amino-acid GHRH 1-44 analog (molecular formula C221H366N72O67S, molecular weight 5135.86 g/mol, CAS 218949-48-5 free base / 901758-09-6 acetate, PubChem CID 16137828) bearing a trans-3-hexenoyl modification on the α-amine of N-terminal Tyr1. Ipamorelin is a synthetic pentapeptide (H-Aib-His-D-2Nal-D-Phe-Lys-NH2; molecular formula C38H49N9O5, molecular weight 711.86 g/mol, CAS 170851-70-4, PubChem CID 11226745) with non-proteinogenic alpha-aminoisobutyric acid at position 1 and D-isomer residues at positions 3 (D-2-naphthylalanine) and 4 (D-phenylalanine). Each component is manufactured by Fmoc solid-phase peptide synthesis on Rink amide resin (yielding the required C-terminal amide), purified to ≥98% by preparative reversed-phase HPLC, and characterized by RP-HPLC at 220 nm and 280 nm plus ESI-MS deconvolution. Per-batch Certificates of Analysis include identity, purity, residual solvent, counter-ion identity, and endotoxin testing for each component. Refer to the individual tesamorelin and ipamorelin PDP entries for full per-component chemistry, synthesis, and analytical specifications.

Tesamorelin Research Summary

Tesamorelin is a synthetic 44-amino-acid analog of GHRH 1-44 discovered at Theratechnologies in Montreal in 1995 under the development code TH9507. The molecule carries one structural distinction from the native parent: a trans-3-hexenoic acid moiety amide-coupled to the α-amine of N-terminal Tyr1. The hexenoyl cap sterically blocks dipeptidyl peptidase IV access to the Tyr1-Ala2 cleavage site while preserving the full 44-amino-acid sequence and the pulsatile GHRH-receptor signaling mode of the native parent^[1][2]. Tesamorelin is the active drug substance in Egrifta (Theratechnologies, NDA 022505), approved by the FDA on November 10, 2010 for reduction of excess abdominal fat in HIV-infected adults with lipodystrophy. That is the only FDA-approved indication.

The Phase 3 evidence base supporting the November 10, 2010 approval comprised two identically-designed Phase 3 placebo-controlled trials. Falutz et al. 2007 in the New England Journal of Medicine (NCT00123253, n = 412 HIV-infected adults, 2:1 tesamorelin to placebo, 26-week primary phase) reported visceral adipose tissue change by CT as -15.2% with tesamorelin versus +5.0% with placebo, with concurrent IGF-1 elevation of 81% from baseline versus -5% on placebo^[6]. Falutz et al. 2010 in J Clin Endocrinol Metab pooled the original Phase 3 with the confirmatory NCT00435136 (combined n = 816) and reported sustained visceral-adipose-tissue reduction over 52 weeks alongside broadly stable glucose parameters^[7].

The Massachusetts General Hospital research program led by Steven K. Grinspoon has run a sustained academic investigation of tesamorelin in HIV-associated nonalcoholic fatty liver disease extending beyond the FDA-approved indication. The Stanley et al. 2019 Lancet HIV trial (NCT02196831, n = 61 HIV-infected adults with hepatic fat fraction ≥ 5%) reported hepatic fat fraction by 1H-MR spectroscopy of -4.1% absolute on tesamorelin versus placebo, 35% of tesamorelin recipients reaching HFF below 5% versus 4% on placebo, and fibrosis progression of 10.5% versus 37.5% on placebo^[9]. A separate single-center Phase 2 trial in mild cognitive impairment and healthy aging (Baker et al. 2012 Arch Neurol, n = 152 adults aged 55-87) examined cognitive outcomes at the University of Washington^[18]; the cognition signal has not been replicated at Phase 3 scale.

Egrifta SV (F4) was approved in 2019 with reduced reconstitution volume. Egrifta WR (F8) was approved March 25, 2025 with weekly reconstitution; US patent protection on F8 extends through 2033^[12]. Tesamorelin was reclassified as a biologic under the BPCIA on March 23, 2020, which closes the 503A bulks-list compounding pathway available to other unapproved drug substances.

Ipamorelin Research Summary

Ipamorelin is a synthetic pentapeptide GHS-R1a agonist designed at Novo Nordisk in the mid-1990s as a receptor-selective successor to the GHRP-1, GHRP-2, GHRP-6, Hexarelin lineage developed through the GHRP discovery work of Cyril Y. Bowers (Tulane) and Frank Reynolds^[5]. The structural moves yielding the reported selectivity were the alpha-aminoisobutyric acid (Aib) N-cap and deletion of the GHRP-1 central Ala-Trp dipeptide^[15]. Raun et al. 1998 reported low-nanomolar GHS-R1a binding affinity and growth hormone release at potency comparable to GHRP-6 in rat pituitary cells, anesthetized rats, and conscious swine, with no detectable elevation of plasma ACTH, cortisol, prolactin, FSH, LH, or TSH at doses greater than 200-fold above the GH ED50^[3].

The selectivity claim is animal-only. The cortisol comparator in Raun 1998 was GHRH rather than vehicle, limiting the resolution of an ipamorelin-specific cortisol signal smaller than the (zero) GHRH-driven signal. The most-cited human pharmacokinetic study (Gobburu et al. 1999, plasma half-life approximately two hours intravenous in healthy male volunteers) measured growth hormone release as the sole pharmacodynamic readout and did not measure plasma cortisol, ACTH, or prolactin^[4]. The reported selectivity is intra-pituitary (somatotroph relative to corticotroph and lactotroph), not inter-organ; GHS-R1a is also expressed in hypothalamus, hippocampus, cardiac tissue, pancreas, immune cells, adipose tissue, and bone. Whether chronic administration produces GHS-R1a tachyphylaxis at research-use dosing patterns has not been characterized in published literature.

The single Phase 2 human-efficacy trial of ipamorelin in any indication (Beck et al. 2014, NCT00672074, postoperative ileus, n = 114 to 117 mITT) reported the pre-specified primary endpoint of median time to first tolerated meal as 25.3 hours on ipamorelin versus 32.6 hours on placebo, p = 0.15^[8]. The trial missed its primary endpoint, Helsinn discontinued ipamorelin development, and no Phase 3 trial in any indication has ever been attempted by any sponsor.

The FDA Pharmacy Compounding Advisory Committee voted against 503A bulks-list inclusion for ipamorelin on October 29, 2024 for both acetate and free-base forms and for both proposed indications (growth hormone deficiency; postoperative ileus); the briefing document recommended against inclusion^[10]. The same Helsinn pivoted to anamorelin, an oral nonpeptide GHS-R1a successor that achieved Japan PMDA approval in January 2021 for cancer cachexia (launched April 2021 via Ono Pharmaceutical), while the EMA refused marketing authorization in 2017 and the FDA issued a Complete Response Letter the sponsor never resubmitted^[19]. Anamorelin's clinical record cannot be imported to ipamorelin claims; the molecules differ in chemistry, route, and indication.

GHRH + GHS-R Pharmacology

The GHRH receptor (GHRH-R) is a class B G-protein-coupled receptor expressed on anterior pituitary somatotrophs. Receptor binding activates Gαs/cAMP/PKA signaling, with downstream activation of GH gene transcription and exocytosis of pre-formed growth hormone from secretory granules^[2]. The growth hormone secretagogue receptor type 1a (GHS-R1a) is a class A G-protein-coupled receptor expressed on the same anterior pituitary somatotroph population (and extensively in the hypothalamus, hippocampus, cardiac tissue, pancreas, immune cells, adipose tissue, and bone). Receptor binding activates Gαq/PLC/IP3/Ca²⁺ signaling and antagonizes hypothalamic somatostatin tone^[3]. The two receptors are coupled to different heterotrimeric G-proteins and different second-messenger cascades, but converge on the same end-cell population for growth hormone release.

The Bowers and colleagues canonical work across the 1980s and 1990s reported that co-administration of a GHRH-R agonist with a GHRP-class agent produced greater growth hormone release than either compound alone in healthy human volunteers, with the synergy mechanism interpreted as pulse-amplitude (GHRH-R) versus basal-frequency (GHS-R1a) control of pituitary somatotroph release plus differential engagement of the somatostatin tone^[5]. The Bowers synergy literature used non-tesamorelin GHRH analogs (sermorelin, native GHRH) plus non-ipamorelin GHRPs (GHRP-2, GHRP-6, Hexarelin). The class-pharmacology framework is biologically supported at the receptor-coupling level. No peer-reviewed RCT of the tesamorelin-plus-ipamorelin specific pairing has ever been conducted. Whether the GHRH-R-plus-GHS-R1a class pharmacology observed by Bowers with sermorelin-plus-GHRP-6 (or related compositions) translates quantitatively to the tesamorelin-plus-ipamorelin pairing under the pharmacokinetic profile of subcutaneous administration (tesamorelin half-life approximately 26 to 38 minutes; ipamorelin half-life approximately two hours intravenous) has not been characterized in the published peer-reviewed literature.

Combined Administration Literature

No peer-reviewed randomized controlled trial of combined tesamorelin plus ipamorelin administration has been conducted in any species. As of May 2026, a PubMed search for trials examining the specific tesamorelin-plus-ipamorelin pairing returns zero results. The published Phase 1, Phase 2, and Phase 3 clinical evidence supporting the November 10, 2010 FDA approval of Egrifta (Falutz 2007 NEJM; Falutz 2010 JCEM pooled analysis; combined n = 816 HIV-infected adults with lipodystrophy) was generated with tesamorelin monotherapy^[6][7]. The Massachusetts General Hospital / Steven Grinspoon program in HIV-associated NAFLD (Stanley 2014 JAMA n = 50; Stanley 2019 Lancet HIV n = 61) was conducted with tesamorelin monotherapy^[9][11]. The single Phase 2 human-efficacy trial of ipamorelin in any indication (Beck 2014 NCT00672074 postoperative ileus, n = 114 to 117 mITT) was conducted with ipamorelin monotherapy and missed its pre-specified primary endpoint at p = 0.15^[8].

Combined administration of tesamorelin with ipamorelin is therefore off-label for tesamorelin's FDA-approved HIV-lipodystrophy indication. It is not an approved indication in any jurisdiction, has not been adjudicated by any regulatory authority, and has no peer-reviewed clinical-trial evidence base in any species. The class-pharmacology observations described in the Pharmacology section above are inferences from non-combined evidence on different molecule pairings. The published clinical-trial evidence describing tesamorelin's safety and efficacy applies to tesamorelin monotherapy in HIV-infected adults with lipodystrophy under cGMP-manufactured Egrifta. It does not extend to combined administration with ipamorelin, to non-HIV general populations, to compounded or research-grade tesamorelin, or to any indication outside the narrow FDA-approved label.

Approved-Drug Context & Status

Tesamorelin's regulatory posture is structurally distinct from every other peptide in the research-supply channel. The FDA-approved indication for Egrifta is narrow: reduction of excess abdominal fat in HIV-infected adults with lipodystrophy. Three FDA-approved formulations exist: original Egrifta (F1, approved November 10, 2010), Egrifta SV (F4, approved 2019, reduced reconstitution volume), and Egrifta WR (F8, approved March 25, 2025, weekly reconstitution and reduced administration volume relative to F4)^[12]. Tesamorelin was reclassified as a biologic under the Biologics Price Competition and Innovation Act of 2009 on March 23, 2020, which closes the 503A bulks-list compounding pathway available to BPC-157, TB-500, GHK-Cu, and other unapproved drug substances. Patient-specific 503A compounding remains theoretically possible with a valid individual prescription. Tesamorelin was not named in the 2020 Tailor Made Compounding plea agreement or the April 1, 2026 Watkins federal indictment in the District of Utah. F8 patent protection in the United States extends through 2033.

Ipamorelin's regulatory posture is the inverse of tesamorelin's on every relevant dimension. The molecule has no FDA approval in any indication. The FDA Pharmacy Compounding Advisory Committee (PCAC) voted against 503A bulks-list inclusion on October 29, 2024 for both the acetate and free-base forms and for both proposed indications (growth hormone deficiency; postoperative ileus); the FDA briefing document itself recommended against inclusion^[10]. Ipamorelin is not scheduled for the July 23-24, 2026 PCAC docket. The 503A door is closed for ipamorelin. Ipamorelin was named explicitly in the 2020 Tailor Made Compounding plea and in the April 1, 2026 Watkins federal indictment alongside CJC-1295, BPC-157, TB-500, GHK, GHK-Cu, NAD+, and GLP-1 analogs as substances at issue in the misbranding charges^[13]. The World Anti-Doping Agency lists ipamorelin explicitly under S2 (Growth Hormone Secretagogues), prohibited at all times in all sports with no Therapeutic Use Exemption pathway; tesamorelin is banned at all times under WADA S2.2.4 (Growth Hormone Releasing Factors)^[14]. Combined administration of the two molecules carries the regulatory implications of both components. The combined preparation is sold strictly for laboratory research use only and is not represented as FDA-approved Egrifta or as any approved therapeutic.