Tesamorelin
A synthetic GHRH analogue and the only one with active FDA approval, indicated for reducing visceral fat in HIV-associated lipodystrophy (marketed as Egrifta). Modified with a trans-3-hexenoic acid group on the full 44-amino-acid GHRH sequence for improved receptor binding affinity. Widely used off-label for body composition improvement and reduction of visceral adipose tissue.
Typical Dosage
FDA-approved: 2 mg subcutaneous once daily in the abdomen. Off-label protocols may vary. Injection site should be rotated within the abdominal area.
Administration
Subcutaneous injection (daily, abdominal)
Mechanism of Action
Tesamorelin is a synthetic GHRH analogue consisting of all 44 amino acids of human GHRH with a trans-3-hexenoic acid group attached to the tyrosine at position 1. This lipophilic modification enhances receptor binding affinity and provides modest resistance to dipeptidyl peptidase-IV (DPP-IV) cleavage, improving its pharmacokinetic profile compared to native GHRH.
Like other GHRH analogues, tesamorelin activates the GHRH receptor on pituitary somatotrophs via the Gs/cAMP/PKA pathway, stimulating endogenous GH synthesis and pulsatile secretion. The resulting increase in circulating GH and IGF-1 produces its primary therapeutic effect: targeted reduction of visceral adipose tissue (VAT). GH-mediated lipolysis is particularly active in visceral fat depots because these adipocytes have the highest density of GH receptors and are most responsive to GH-stimulated hormone-sensitive lipase activation.
The specificity of tesamorelin's effect on visceral rather than subcutaneous fat has been well-documented in clinical trials. Visceral adipose tissue is metabolically distinct — it drains directly into the portal circulation and contributes disproportionately to hepatic insulin resistance, inflammatory cytokine production, and cardiovascular risk. By selectively reducing this depot, tesamorelin improves the cardiometabolic profile beyond what would be expected from total fat loss alone. Clinical trials also showed improvements in hepatic steatosis (fatty liver) markers, triglyceride levels, and trunk fat distribution. It remains the only GHRH analogue with active FDA approval, specifically for HIV-associated lipodystrophy, where visceral fat accumulation is a common and distressing side effect of antiretroviral therapy.
Regulatory Status
FDA approved (2010) as Egrifta for HIV-associated lipodystrophy. Theratechnologies. Off-label use for body composition and NAFLD.
Risks & Safety
Common: injection site reactions (erythema, pruritus, pain), joint pain (arthralgia), peripheral edema, muscle pain (myalgia), paresthesia. Serious: impaired glucose tolerance and insulin resistance, potential acceleration of existing tumors via GH/IGF-1 elevation. Rare: hypersensitivity reactions, carpal tunnel syndrome. Contraindicated in active malignancy, pregnancy, and disruption of the hypothalamic-pituitary axis from hypophysectomy or radiation. FDA approved.
Research Papers
6Published: January 8, 2026
Abstract
Introduction: Overweight and obesity are becoming increasingly prevalent. Incretin-based obesity treatments-glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucagon-like peptide-1 receptor/glucose-dependent insulinotropic polypeptide receptor agonists (GIP/GLP-1 RAs or dual agonists)-are a major stride in the evolution of obesity management. However, like weight loss with other means, they are associated with an inadvertent significant loss of lean body mass, including muscle. This has led to a resurgence in research for the preservation of lean body mass, the loss of which occurs with weight loss. The purpose of this narrative review is to discuss the mechanisms involved with lean body loss and capture the research landscape of the different classes of pharmacological agents being developed to address this problem. Methodology: We queried PubMed, Medline, and Scopus for randomized controlled trials and phase II or phase III trials using key words to capture the breath of this topic-obesity, weight loss, muscle loss, lean mass, and muscle preservation. Animal studies were excluded. We analyzed the studies conducted to date. Results: Weight loss, regardless of the method used to achieve it, is inadvertently accompanied by lean body mass loss, to varying degrees. There are several mechanisms that govern the loss of lean body mass and, more specifically, the loss of muscle mass; as such, several classes of medications have been explored, targeting different pathways and receptors-including bimagrumab (activin receptor agonist), tesamorelin (growth hormone releasing hormone agonists), and enobosarm (selective androgen receptor modulator). Most of these drugs are in the early phases of research development, but some show great promise. Conclusion: This narrative review attempts to detail the physiology of muscle mass loss when accompanied by weight loss and identify pharmacological targets that can be utilized to minimize it with mechanisms, effects, side effects, and research developmental progress.
Published: January 15, 2026
Abstract
HIV-associated lipodystrophy leads to visceral fat accumulation, metabolic complications, body image concerns, medication non-adherence, and increased cardiovascular risks. We thought to assess the effects of Tesamorelin, a synthetic growth hormone-releasing hormone analogue, that has been proposed as a targeted therapy.
Published: 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.
Published: January 14, 2026
Abstract
Growth hormone-releasing hormone (GHRH) and its synthetic analogs are considered performance-enhancing substances and are therefore prohibited by the World Anti-Doping Agency (WADA). The analysis of GHRH and its analogs in urine presents significant analytical challenges due to their inherent in vivo instability, rapid renal clearance, and low urinary concentrations. The present study aimed to develop a robust nano-LC quadrupole/orbitrap mass spectrometry (nano-LC-Q/Orbitrap MS) method for both screening and confirmation analyses of GHRH and its synthetic analogs (sermorelin/CJC-1293, tesamorelin, and CJC-1295) and the primary metabolite of sermorelin in urine, in accordance with WADA requirements. The sample preparation workflow was systematically investigated. Existing solid-phase extraction (SPE) protocols were compared, and two additional commercially available SPE cartridges were evaluated. Within the SPE step, the influence of various washing and elution solvent strengths on peptide recovery was also systematically examined. The effectiveness of different cleanup solvents during the ultrafiltration step was further assessed. Based on these evaluations, a refined approach was developed, incorporating an initial ultrafiltration step followed by SPE. The proposed method was fully validated according to WADA guidelines, assessing key parameters such as selectivity, reliability, limits of detection (LOD), carryover, limits of identification (LOI), robustness, autosampler stability, and matrix effects. The validation results confirmed the method's suitability and robustness for anti-doping testing. Achieved LODs (≤ 0.5 ng/mL) and LOIs (0.5-0.75 ng/mL) demonstrated sufficient sensitivity for effective detection and confirmation analysis of the target peptides in urine.
Published: June 30, 2025
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among people with HIV (PWH) and increasingly recognized as a major contributor to morbidity and mortality. The field of MASLD is rapidly evolving with adoption of a new nomenclature and approval of the first FDA-approved therapy within the past year. These developments underscore the need to consider the current state of the science specifically in the context of HIV.
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