Sermorelin vs Tesamorelin
Sermorelin and tesamorelin are both analogues of growth hormone-releasing hormone. Sermorelin is the 29-residue active fragment and was once FDA-approved; tesamorelin is the full 44-residue sequence with an N-terminal modification and remains FDA-approved as Egrifta.
Sermorelin and tesamorelin both act at the growth hormone-releasing hormone (GHRH) receptor on pituitary somatotrophs. They differ in length, in chemical modification and in regulatory history.
Sermorelin corresponds to the first 29 residues of human GHRH, the shortest fragment with full receptor activity, with a C-terminal amide. It was previously approved in the United States as Geref but was discontinued. Tesamorelin keeps the full 44-residue GHRH sequence and adds a trans-3-hexenoyl group to the N-terminus, which improves resistance to enzymatic breakdown. It is FDA-approved as Egrifta to reduce excess abdominal fat in HIV-associated lipodystrophy.
Side-by-side
| Attribute | Sermorelin | Tesamorelin |
|---|---|---|
| Origin | GHRH(1-29) fragment of human GHRH | Full-length human GHRH(1-44) |
| Length | 29 residues | 44 residues |
| Modifications | C-terminal amide; no N-terminal modification | N-terminal trans-3-hexenoyl group; C-terminal amide |
| Target | GHRH receptor | GHRH receptor |
| Stability rationale | Native-like sequence; susceptible to DPP-4 cleavage at the N-terminus | N-terminal acylation reduces DPP-4 cleavage |
| Clinical history | Previously approved (Geref); discontinued in the US | Approved (Egrifta) for HIV-associated abdominal fat; phase 3 program completed |
| Evidence level | Approved (historical) | Approved |
| WADA | Prohibited under S2 (GHRH analogues) | Prohibited under S2 (GHRH analogues) |
| Analytical pitfalls | Met and Asn residues: oxidation and deamidation | Same oxidation and deamidation risks; confirm the hexenoyl group is present by mass |
Fragment vs full-length
Native GHRH is 44 residues long, but structure-activity work showed that the N-terminal 29 residues keep full receptor activity. Sermorelin is that fragment. Tesamorelin keeps all 44 residues, so it is a larger molecule with a different expected mass and its own impurity profile. Both depend on an intact N-terminus for activity, which makes the first two residues a key point of vulnerability.
Why the N-terminal modification matters
Dipeptidyl peptidase-4 cleaves native GHRH between residues 2 and 3 and inactivates it. Tesamorelin's trans-3-hexenoyl group on the N-terminal tyrosine was designed to reduce this cleavage and prolong activity. Sermorelin lacks any such protection, which is one reason other analogues, such as CJC-1295, introduce amino acid substitutions instead. When analyzing tesamorelin, the mass should confirm the acyl group, since an unacylated 44-residue peptide is a different compound.
Regulatory contrast
Tesamorelin is a currently approved drug with a defined indication and a completed phase 3 clinical program in HIV-associated lipodystrophy. Sermorelin was approved in the past but is no longer marketed in the United States. Its earlier approval does not make it a currently approved product. Both fall under the WADA S2 class of GHRH analogues.
Frequently asked questions
What is the difference between sermorelin and tesamorelin?
Sermorelin is the 29-residue N-terminal fragment of growth hormone-releasing hormone, while tesamorelin is the full 44-residue sequence with an added trans-3-hexenoyl group at the N-terminus. Both act at the GHRH receptor. Tesamorelin is FDA-approved as Egrifta; sermorelin was approved as Geref but has been discontinued in the US.
Is tesamorelin FDA approved?
Yes. Tesamorelin is FDA-approved as Egrifta to reduce excess abdominal fat in people with HIV-associated lipodystrophy. That approval covers only the specified indication and formulation.
Is sermorelin still approved?
Sermorelin was previously approved in the United States as Geref, but the product was discontinued. It is therefore not a currently marketed approved drug in the US. Its current status in compounding and elsewhere should be checked with up-to-date regulatory sources.
Full entries
- Sermorelin
Sermorelin is a synthetic peptide consisting of the first 29 amino acids of human growth hormone releasing hormone (GHRH). It was previously FDA-approved as Geref but has been discontinued in the US.
- Tesamorelin
Tesamorelin is a stabilized synthetic analogue of human growth hormone releasing hormone. It is FDA-approved as Egrifta for reducing excess abdominal fat in adults with HIV-associated lipodystrophy.
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