Tesamorelin + Ipamorelin
A popular combination pairing the FDA-approved GHRH analogue Tesamorelin with the selective ghrelin-mimetic Ipamorelin for enhanced growth hormone release. Favored for body composition improvement, visceral fat reduction, and anti-aging. Tesamorelin's proven clinical efficacy for visceral fat reduction combined with Ipamorelin's clean side-effect profile makes this a premium GH peptide protocol.
Typical Dosage
Standard: Tesamorelin 1-2 mg + Ipamorelin 100-300 mcg subcutaneous once daily, typically before bed. Often cycled 12 weeks on, 4 weeks off.
Administration
Subcutaneous injection (daily)
Mechanism of Action
The Tesamorelin + Ipamorelin combination pairs the only FDA-approved GHRH analogue with the most selective growth hormone secretagogue, creating a dual-pathway approach similar in principle to CJC-1295/Ipamorelin but with tesamorelin's unique advantages for body composition.
Tesamorelin activates the GHRH receptor on pituitary somatotrophs through the Gs/cAMP/PKA pathway, stimulating GH gene transcription and secretion. Its trans-3-hexenoic acid modification at position 1 provides enhanced receptor affinity and modest DPP-IV resistance compared to native GHRH. Ipamorelin simultaneously activates the GHS-R1a receptor via the Gq/11/PLC/calcium pathway, providing the same synergistic amplification of GH pulses described for the CJC/Ipa combination.
The distinguishing advantage of tesamorelin in this stack is its clinically demonstrated effect on visceral adipose tissue (VAT). In multiple randomized controlled trials for HIV-associated lipodystrophy, tesamorelin reduced trunk fat by 15-18% over 6 months, with visceral fat reduction being proportionally greater than subcutaneous fat reduction. This preferential visceral fat mobilization occurs because visceral adipocytes express the highest density of GH receptors and are most responsive to GH-mediated hormone-sensitive lipase activation. The GH elevations produced by tesamorelin/ipamorelin combination may be greater than tesamorelin alone (due to the synergistic dual-pathway effect), potentially enhancing this visceral fat-targeting effect. The combination also benefits from tesamorelin's full-length GHRH sequence (44 amino acids vs 29 for CJC-1295), which may provide more complete receptor activation, and from the preserved pulsatility that both agents maintain through intact somatostatin feedback regulation.
Regulatory Status
Tesamorelin is FDA approved (Egrifta) for HIV-associated lipodystrophy. Ipamorelin is not FDA approved. The combination is prescribed off-label through compounding pharmacies.
Risks & Safety
Common: injection site reactions (erythema, pain), joint pain (arthralgia), peripheral edema, paresthesia, headache. Serious: impaired glucose tolerance from sustained GH elevation, potential promotion of existing tumors. Rare: carpal tunnel syndrome, severe hypersensitivity. Tesamorelin contraindicated in pregnancy and active malignancy. Not FDA approved as a combination product.
Research Papers
2Published: December 31, 2025
Abstract
Therapeutic peptides are emerging as promising adjuncts in the management of orthopaedic injuries, grounded in their ability to modulate molecular signaling networks central to cellular medicine. By acting on key pathways such as PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK, peptides exert influence over tissue regeneration, inflammation resolution, and neuromuscular recovery. Wound-healing peptides such as BPC-157, TB-500, and GHK-Cu promote angiogenesis, integrin-mediated extracellular matrix remodeling, and fibroblast activation, whereas growth hormone secretagogues like ipamorelin, CJC-1295, tesamorelin, sermorelin, and AOD-9604 activate IGF-1 signaling and satellite cell repair. Recovery-enhancing agents such as epithalon, delta sleep-inducing peptide, and pinealon target circadian and mitochondrial regulators, and neuroactive peptides like selank, semax, and dihexa enhance brain-derived neurotrophic factor and HGF/c-Met pathways critical to neuroplasticity. Although preclinical studies are promising, there is a current lack of clinical trials. This review integrates current mechanistic insights with orthopaedic relevance, emphasizing safety, efficacy, and future directions for responsible integration into musculoskeletal care.
Published: December 31, 2025
Abstract
Therapeutic peptides are short-chain amino acids that regulate cellular functions and facilitate biochemical processes. In recent years, there has been significant growth in the global market for therapeutic peptides and thus its popularity among patients. Given the increase in the development of peptides and increased marketing to patients for orthopaedic injuries, it is critical for orthopaedic surgeons to understand the current evidence behind these therapeutic peptides.
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