What is tesamorelin? Tesamorelin is a synthetic growth hormone–releasing hormone (GHRH) analogue (brand EGRIFTA SV) used to reduce visceral abdominal fat (VAT) in adults with HIV-associated lipodystrophy. It works by stimulating pulsatile growth hormone (GH) release, which secondarily raises insulin‑like growth factor‑1 (IGF‑1). In this article, we explain how it works, what outcomes are realistic, how it compares to related peptides, and how researchers handle it in studies. This is educational content, not medical advice. (FDA Access Data)
Fast Answer / Executive Summary (40–60 words)
Tesamorelin is a GHRH analogue that reduces visceral adipose tissue by ~15–20% over 26–52 weeks in HIV‑associated lipodystrophy while largely sparing subcutaneous fat; effects extend to modest liver‑fat reductions and better triglycerides in responders. It differs from giving GH directly by preserving physiologic feedback and, in trials, did not worsen glycemic control in type 2 diabetes. (Oxford Academic)
Tesamorelin — Entity Properties (for researchers)
| Property | Details (standardized) |
|---|---|
| Aliases / Synonyms | Tesamorelin; TH9507; EGRIFTA/EGRIFTA SV (tesamorelin for injection) |
| Family / Pathway | GHRH analogue → GHRH receptor (pituitary somatotrophs) → pulsatile GH → hepatic IGF‑1 |
| Sequence (AA) | 44‑AA analogue of GHRH(1‑44) with N‑terminal trans‑3‑hexenoyl on Tyr¹ (resists DPP‑IV) |
| Molecular Weight (Da) | 5135.9 (free base); ~5579 (acetate salt) |
| CAS | Tesamorelin (free base): 218949‑48‑5; Tesamorelin acetate: 901758‑09‑6 |
| Typical Diluent(s) | Sterile Water for Injection (per EGRIFTA SV labeling) |
| Example Concentration(s) | EGRIFTA SV: reconstitute 2 mg vial with 0.5 mL → 4 mg/mL; dose 1.4 mg (0.35 mL) SC once daily |
| Storage (lyophilized / after reconstitution) | EGRIFTA SV vials: room temp (20–25°C), protect from light; use immediately after reconstitution; discard unused solution |
Sources: FDA chemistry review (composition, MW), FDA labeling (diluent, storage, dosing), PubChem (CAS), and nonclinical pharmacology (hexenoyl modification & DPP‑IV resistance).
Core Concepts & Key Entities
What tesamorelin is (and how it works)
Tesamorelin is a stabilized 44‑amino‑acid GHRH analogue that binds the GHRH receptor to restore physiologic GH pulses, thereby increasing IGF‑1 and favoring lipid mobilization in visceral depots. A trans‑3‑hexenoyl group on Tyr¹ confers partial resistance to DPP‑IV cleavage, improving exposure relative to native GHRH. (FDA Access Data)
Why this matters for outcomes: Compared with exogenous GH, a GHRH analogue preserves hypothalamic–pituitary feedback, allowing IGF‑1–mediated self‑limiting control of GH output. That physiologic gating helps explain why tesamorelin reduces VAT while generally sparing subcutaneous fat and with fewer glucose‑metabolism penalties than direct GH. (Oxford Academic)
What outcomes can researchers expect?
VAT reduction is the primary, most reproducible outcome. Across phase 3 trials, tesamorelin lowered VAT by ~15–20% at 26 weeks, and the reduction was maintained through 52 weeks when therapy continued, with no clinically significant loss of subcutaneous fat. Patient‑reported belly profile and body‑image distress improved. (Oxford Academic)
Metabolic markers track with response magnitude. In a pooled analysis, responders with ≥8% VAT loss showed lower triglycerides and higher adiponectin, without worsened glucose homeostasis, highlighting that “how much VAT you remove” predicts downstream metabolic benefit. (PMC)
Liver outcomes (HIV‑associated NAFLD/MASLD). In randomized trials, tesamorelin reduced liver fat and slowed fibrosis progression in people with HIV and fatty liver disease—important given the overlap of VAT expansion and hepatic steatosis in this population. (JAMA Network)
Pharmacokinetics to know (why some data differ)
Absorption is rapid (Tmax ~0.15 h). Bioavailability is low (<4%), consistent with peptide degradation and local absorption kinetics. Half‑life is short and formulation‑dependent: ~8 minutes with EGRIFTA SV (2 mg/vial) in healthy subjects, versus ~26–38 minutes reported with the prior 1 mg/vial formulation after repeated dosing. Mechanistically the drug’s effect outlasts plasma levels by stimulating a GH pulse sequence. (FDA Access Data)
Safety signals to monitor (educational)
Common effects include injection‑site reactions, arthralgia, peripheral edema, and myalgia; IGF‑1 rises predictably. Glucose: labels warn about glucose intolerance, but a 12‑week randomized trial in type 2 diabetes found no deterioration in insulin response or glycemic control at the approved exposure. Contraindications include active malignancy, pregnancy, and disruption of the hypothalamic‑pituitary axis. (FDA Access Data)
Antibodies occur but don’t appear to blunt VAT response. Anti‑tesamorelin IgG was detected in ~50% (week 26) and ~47% (week 52) with cross‑reactivity to endogenous GHRH in ~60%, yet VAT and IGF‑1 responses were similar between antibody‑positive and ‑negative subjects. Neutralizing antibodies were less common. (FDA Access Data)
Why not just give GH? Exogenous GH can reduce insulin sensitivity acutely and at months, even as body composition improves—an effect linked to lipolysis and substrate competition. In contrast, tesamorelin’s GHRH‑mediated physiology has shown neutral glycemic effects in T2D over 12 weeks and no sustained fasting glucose rise after early transient changes in some HIV cohorts. (PubMed)
Who tends to respond best?
A post‑hoc analysis found VAT reductions were more likely in participants with baseline metabolic syndrome (NCEP), elevated triglycerides, and in some demographic strata. This can guide study stratification and early‑stop rules (e.g., continue if ≥8% VAT reduction by 26 weeks). (PLOS)
Step‑by‑Step / How‑To (for researchers; educational)
The steps below outline how researchers typically design and execute tesamorelin protocols. Always follow IRB/ethics, manufacturer instructions, and local regulations; this is not medical advice.
1) Define the objective and endpoint
Frame a primary endpoint that reflects visceral adiposity (e.g., single‑slice L4‑L5 CT VAT area, or MRI‑PDFF if focusing on liver). Pre‑specify a clinically meaningful VAT change (e.g., ≥8% reduction) because this threshold aligns with favorable triglyceride/adiponectin shifts. (PubMed)
2) Choose vial size and a dosing schedule (educational)
Regulatory trials used once‑daily SC dosing. For protocol planning, PeptideDosages.com maintains educational vial‑specific pages researchers consult when modeling draw volumes and dilutions: Tesamorelin 5 mg protocol, 10 mg, 20 mg. (Educational links; not prescribing.)
3) Handle and reconstitute correctly
Follow the approved Instructions for Use: reconstitute EGRIFTA SV 2 mg vial with 0.5 mL Sterile Water for Injection, gently roll (do not shake), confirm a clear solution, and administer immediately (0.35 mL = 1.4 mg). Discard unused solution. (FDA Access Data)
4) Administer subcutaneously with site rotation
Inject into the abdomen; rotate sites and avoid the navel, scars, or bruised areas. Document lot, site, and timing to align samples with GH pulse windows if you’re measuring pharmacodynamic markers. (FDA Access Data)
5) Baseline phenotyping
Before first dose, capture VAT (CT/MRI), waist circumference, fasting lipids, glucose/HbA1c, IGF‑1, and liver fat (MRI‑PDFF) if NAFLD is an outcome. This mirrors endpoints used in pivotal studies and facilitates responder analysis. (Oxford Academic)
6) Interim checks (2–12 weeks)
Expect IGF‑1 to rise; fasting glucose may show a transient early increase that is not sustained. Record adverse events (edema, arthralgia, injection reactions). Adjust study monitoring per protocol if IGF‑1 exceeds reference ranges or if glucose worsens. (JAMA Network)
7) Efficacy assessment (~26 weeks)
Re‑image VAT. If ≥8% reduction, anticipate greater improvements in triglycerides/adiponectin—and consider continuation phases to test durability to 52 weeks. If <8%, pre‑planned protocol decisions (continue vs. discontinue) help maintain scientific clarity. (PubMed)
8) Liver‑specific substudies
In HIV with fatty liver disease, include MRI‑PDFF and noninvasive fibrosis markers. Tesamorelin has reduced liver fat and slowed fibrosis progression in randomized data. (The Lancet)
9) Immunogenicity tracking (exploratory)
If feasible, archive serum for anti‑drug antibody testing; antibodies occur frequently but did not blunt VAT/IGF‑1 responses in trials. (FDA Access Data)
10) Storage & documentation
Store lyophilized vials at controlled room temperature (20–25°C), protect from light, and do not store reconstituted solution (use immediately). Record chain‑of‑custody and reconciliation for audit. (FDA Access Data)
Comparison / Alternatives (“Is tesamorelin better than X?”)
Short answer: For visceral adiposity in HIV‑associated lipodystrophy, tesamorelin is the only FDA‑approved peptide with RCT evidence of VAT reduction and liver‑fat benefits. Other peptides act on the GH axis but lack comparable VAT‑targeted, HIV‑specific outcomes in randomized trials. GLP‑1 receptor agonists (e.g., semaglutide) improve steatohepatitis in non‑HIV populations, but they are not GHRH analogues and serve different indications. (PMC)
Snapshot Table — Tesamorelin vs. Sermorelin vs. CJC‑1295 (DAC) vs. Ipamorelin (mechanism‑level, educational)
| Feature | Tesamorelin | Sermorelin | CJC‑1295 (DAC) | Ipamorelin |
|---|---|---|---|---|
| Primary target | GHRH receptor agonist | GHRH receptor agonist | Long‑acting GHRH analogue (albumin‑binding via DAC) | Ghrelin/GHSR agonist |
| Key design | GHRH(1‑44) with trans‑3‑hexenoyl on Tyr¹ (DPP‑IV resistant) | GHRH(1‑29) | GHRH analogue with albumin binding | Pentapeptide, selective GH secretagogue |
| Human t½ (approx.) | 8–38 min (formulation‑dependent) | ~8–12 min | ~6–8 days | ~2 hours |
| Dosing cadence | Daily SC (trial paradigm) | Daily SC | Weekly or less often in trials | 1–3×/day in studies |
| VAT reduction RCTs (HIV) | Yes; ~15–20% | None | None | None |
| Glycemic signal | Neutral in 12‑wk T2D RCT; early transient FG rise in some HIV cohorts | Limited data | Limited data | Limited metabolic data |
| Notable safety | IGF‑1 elevation, edema, ISR; label warns on glucose, neoplasms | ISR; short t½ | IGF‑1 rise sustained | Selective GH without ACTH/cortisol rise |
Notes & sources: Design/sequence & DPP‑IV resistance (tesamorelin), human half‑lives, and selectivity derive from FDA documents and peer‑reviewed trials/reviews: tesamorelin labeling and chemistry review; serum t½ for sermorelin; long t½ for CJC‑1295; ipamorelin PK (~2 h) and selectivity (no ACTH/cortisol). VAT data reflect tesamorelin phase 3 RCTs.
Templates / Checklist / Example
Copy‑ready Checklist — Tesamorelin Research Session (educational)
- Confirm eligibility: Inclusion/exclusion consistent with prior RCTs (e.g., fasting glucose parameters; exclude pregnancy, active malignancy). (FDA Access Data)
- Set endpoints: VAT by CT/MRI; optionally MRI‑PDFF for liver. (Oxford Academic)
- Pre‑dose labs: Fasting glucose, HbA1c, lipids, IGF‑1. (Oxford Academic)
- Prepare vial: Reconstitute with Sterile Water for Injection per label; gently roll; ensure clarity. Do not shake. (FDA Access Data)
- Administer dose: Subcutaneous abdominal injection; rotate sites and document site/time. (FDA Access Data)
- Record AEs: Injection‑site reactions, edema, arthralgia, myalgia; counsel on signs of hypersensitivity. (FDA Access Data)
- Early monitoring (week 2): Expect IGF‑1 rise; early fasting glucose blip may occur but was not sustained in RCTs. (JAMA Network)
- Mid‑course decision (≈26 weeks): If VAT ≥8%↓, anticipate more favorable triglyceride/adiponectin; consider continuation phase. (PubMed)
- Liver substudy: Track MRI‑PDFF and fibrosis markers in HIV fatty liver cohorts. (The Lancet)
- Store properly: Vials at 20–25°C, protect from light; use reconstituted dose immediately. (FDA Access Data)
- Document immunogenicity (optional): Bank serum; antibodies common but did not blunt VAT response. (FDA Access Data)
- Report with context: Emphasize physiologic mechanism vs. exogenous GH risks around insulin sensitivity. (PubMed)
FAQs (NLP‑friendly; 40–80 words each)
What is tesamorelin?
Tesamorelin is a synthetic GHRH analogue that stimulates the pituitary to release GH in physiologic pulses, raising IGF‑1 and driving selective visceral fat reduction in adults with HIV‑associated lipodystrophy. It is the only peptide approved for this purpose and has a well‑described RCT evidence base. (FDA Access Data)
How much visceral fat reduction does tesamorelin achieve?
RCTs show ~15–20% VAT reduction after 26–52 weeks, with maintenance of the effect if treatment continues. Subcutaneous fat is largely preserved, and body‑image metrics improve. Responders (≥8% VAT loss) also show better triglycerides and adiponectin. (Oxford Academic)
Does tesamorelin worsen blood sugar control?
Evidence indicates no deterioration of glycemic control in a 12‑week randomized trial in type 2 diabetes; in HIV cohorts, a transient early fasting glucose uptick has been observed but was not sustained. Labeling still advises glucose monitoring. (PMC)
How does tesamorelin affect the liver?
Tesamorelin reduces liver fat and slows fibrosis progression in people with HIV and fatty liver disease, linking VAT reduction to hepatic benefits in this population. (The Lancet)
How is tesamorelin different from giving GH or from GLP‑1 agonists?
Unlike exogenous GH, tesamorelin preserves physiologic feedback and has a distinct glycemic profile; GH therapy can acutely impair insulin sensitivity. Unlike GLP‑1 receptor agonists (e.g., semaglutide) used for obesity/NASH, tesamorelin specifically targets GHRH signaling and VAT in HIV‑associated lipodystrophy. (PubMed)
Next Steps
Bottom line: Tesamorelin is a physiologic GHRH analogue with the strongest RCT evidence for reducing VAT in HIV‑associated lipodystrophy, with emerging liver benefits and a distinct safety/PK profile. If you’re modeling study dosing and dilutions, see our educational guides: 5 mg • 10 mg • 20 mg.
For research supply, explore: Tesamorelin 5 mg • 10 mg • 20 mg (research‑use only).
Compliance note: This article is educational and not medical advice. Always follow official labeling and ethics approvals. (FDA Access Data)