Sermorelin vs Tesamorelin: Approval Status and Evidence

Sermorelin and tesamorelin are often listed side by side as "GH peptides", and they do work the same way: both tell the pituitary to release more of its own growth hormone. Their regulatory stories could hardly be more different. One is a current prescription drug with phase 3 trials behind a narrow indication; the other was approved for children in the 1990s and has not been sold as an FDA-approved product since 2008.

Short answer: tesamorelin is a currently FDA-approved prescription drug (Egrifta SV and Egrifta WR) indicated only to reduce excess abdominal fat in adults with HIV-associated lipodystrophy^3,4. Sermorelin was FDA-approved as Geref, first in 1990 as a diagnostic test and in 1997 to treat growth hormone deficiency in children, but its maker discontinued it in 2008 and FDA withdrew the approvals in 2009¹. FDA later determined that Geref was not withdrawn for reasons of safety or effectiveness¹. Both are GHRH analogs; tesamorelin has far larger and more recent trials.

This is a comparison of approval status and evidence, not a dosing guide. For tesamorelin's label doses and chemistry, see the tesamorelin compound page; to convert a prescribed dose into syringe units, use the tesamorelin calculator.

Sermorelin vs tesamorelin at a glance

Same mechanism, different molecules

The hypothalamus releases GHRH, which signals the pituitary to release growth hormone (GH); GH in turn raises insulin-like growth factor 1 (IGF-1). Both drugs act at the GHRH receptor, so they depend on a working pituitary rather than supplying GH directly. That is why the Egrifta labels list disruption of the hypothalamic-pituitary axis, for example after pituitary surgery, head irradiation or head trauma, as a contraindication³.

The difference is in the molecule. Sermorelin is GHRH(1-29), the shortest synthetic peptide that keeps the full biological activity of the natural hormone¹¹. Tesamorelin keeps all 44 amino acids of human GHRH and adds a hexenoyl moiety, a six-carbon chain, to the tyrosine at the N-terminus³. Even so, tesamorelin is short-lived in the blood: the Egrifta SV label reports a mean elimination half-life of 8 minutes after a single subcutaneous 1.4 mg dose³.

Sermorelin's approval history, verified

According to FDA's 2013 Federal Register notice, Geref (sermorelin acetate) was approved under two applications held by EMD Serono¹:

1. NDA 19-863, approved 28 December 1990: Geref 0.05 mg ampule, for evaluating the pituitary's ability to secrete growth hormone (a diagnostic test)¹.
2. NDA 20-443, approved 26 September 1997: Geref 0.5 mg and 1.0 mg vials, for treating idiopathic growth hormone deficiency in children with growth failure¹.
3. July and December 2008: EMD Serono told FDA both products were being discontinued and asked FDA to withdraw the applications¹.
4. 18 June 2009: FDA's withdrawal of both approvals took effect¹.
5. 4 March 2013: after a citizen petition, FDA determined that Geref was not withdrawn from sale for reasons of safety or effectiveness, which means a generic (ANDA) version could in principle be approved if other requirements are met¹.

The notice does not give a commercial reason for the discontinuation, and neither does this guide. Claims online that sermorelin was pulled "for safety" are contradicted by FDA's determination; claims that it is "FDA-approved" today are also wrong. In FDA's Drugs@FDA data, sermorelin appears only under the two discontinued Geref applications².

Tesamorelin's approval history

Tesamorelin was first approved on 10 November 2010 as Egrifta, a new molecular entity from Theratechnologies². The original product used 1 mg vials at a 2 mg daily dose, the dose studied in the phase 3 trials³. Two reformulations followed. Egrifta SV uses a 2 mg vial, a 1.4 mg daily dose (0.35 mL), and is reconstituted fresh each day³. Egrifta WR, approved in March 2025, uses an 11.6 mg vial reconstituted with bacteriostatic water once a week, then injected at 1.28 mg (0.16 mL) daily^4,5. The two current formulations are not substitutable for each other⁴.

The indication is narrow and the labels spell out its limits: long-term cardiovascular safety has not been established, Egrifta is not indicated for weight loss because its effect is weight neutral, and treatment should be reconsidered in people whose visceral fat does not fall³.

What the tesamorelin trials show

The approval rests on two randomized, double-blind phase 3 trials in adults with HIV and excess abdominal fat. In the first, published in the New England Journal of Medicine, 412 patients received tesamorelin 2 mg or placebo daily for 26 weeks. Visceral fat fell by 15.2% with tesamorelin and rose by 5.0% with placebo; triglycerides fell by 50 mg/dL versus a rise of 9 mg/dL, and IGF-1 rose by 81%⁶. More patients on tesamorelin left the study because of an adverse event⁶.

A pooled analysis of both trials (806 patients) found a treatment effect of −15.4% on visceral fat at 26 weeks, with no significant change in fat under the skin of the abdomen⁷. Patients who stayed on tesamorelin kept the reduction to week 52, about −17.5% from baseline⁷. In the extension, patients who had taken tesamorelin were re-randomized to continue it or switch to placebo for the second 26 weeks^3,7.

Later trials looked at liver fat. In a 6-month trial of 50 people with HIV, tesamorelin reduced visceral fat and liver fat compared with placebo, with a net effect of −2.9% in liver lipid-to-water ratio⁸. In a 12-month trial of 61 people with HIV and non-alcoholic fatty liver disease, the hepatic fat fraction fell by an absolute 4.1% more than placebo, a 37% relative reduction, and 35% of the tesamorelin group versus 4% on placebo ended below the 5% threshold for fatty liver⁹. Liver fat is not an approved indication.

Outside HIV, the largest study is a 20-week trial in 152 older adults, 66 of them with mild cognitive impairment, using tesamorelin 1 mg nightly. Cognitive composite scores improved versus placebo, IGF-1 rose by 117% and body fat fell by 7.4%; adverse events were reported by 68% on tesamorelin versus 36% on placebo¹³. That is one trial, and cognition is not an approved use.

What the sermorelin trials show

Sermorelin's treatment evidence is mostly pediatric. In the Geref International Study Group's open-label study, 110 previously untreated prepubertal children with GH deficiency received 30 μg/kg subcutaneously at bedtime for up to a year. Mean height velocity rose from 4.1 cm/year at baseline to 8.0 cm/year at 6 months and 7.2 cm/year at 12 months, and 74% were judged good responders at 6 months¹⁰. There was no placebo group. A 1999 review concluded that limited data supported once-daily 30 μg/kg in some children, that its effect on final adult height was unknown, and that it had not been compared directly with somatropin at the recommended dose; the most common side effects were facial flushing and injection-site pain¹¹.

Adult data are sparse. In a 6-week study, 11 healthy men aged 64 to 76 injected 2 mg of GHRH(1-29) each night. Nocturnal GH release increased, but IGF-1 did not change; two of six strength measures improved, and weight, body composition and fat did not change¹². The authors concluded that single nightly doses were less effective than multiple daily doses¹².

Side effects and warnings

For tesamorelin, the label is the best source. The most common adverse reactions (over 5%) were joint pain, injection-site redness and itching, pain in the extremities, peripheral swelling and muscle pain³. Injection-site reactions occurred in 25% of treated patients, and hypersensitivity reactions in 4%³. The label also warns about:

1. IGF-1: after 26 weeks, 47% of patients had IGF-1 above 2 standard deviation scores and 36% above 3; the label advises monitoring IGF-1 and considering stopping with persistent elevation³.
2. Glucose: 5% on tesamorelin versus 1% on placebo developed HbA1c of 6.5% or more by week 26; glucose should be checked before and during treatment³.
3. Fluid retention: swelling, joint pain and carpal tunnel syndrome, usually transient or resolving on stopping³.
4. Malignancy: contraindicated in active cancer; any previous cancer should be inactive and treated first³.
5. Pregnancy: contraindicated³.

For sermorelin there is no current FDA label to consult. The pediatric data reported flushing and injection-site pain as the most common effects¹¹, and no change in fasting glucose or excessive IGF-1 in the 1-year study¹⁰. Those findings came from children with GH deficiency on a pharmaceutical product and cannot simply be carried over to adults using compounded sermorelin. Because both drugs raise GH and IGF-1, the same questions about cancer history, glucose and fluid retention apply to both.

Compounding: why sermorelin is still around

U.S. pharmacies can compound drugs for an identified patient with a valid prescription under section 503A of the Food, Drug, and Cosmetic Act¹⁴. The bulk ingredient must meet a USP or National Formulary monograph, be a component of an FDA-approved drug, or appear on FDA's list of bulk substances allowed for compounding¹⁴. Where sermorelin falls under those rules is a regulatory question this guide does not settle. What is clear is the practical result: compounded sermorelin is not an FDA-approved drug, and a given pharmacy's product has not been through FDA review for quality, safety or effectiveness.

Tesamorelin is in a different position because an approved product is on the market. Section 503A bars pharmacies from compounding, regularly or in inordinate amounts, drugs that are essentially copies of a commercially available product, unless a change is made for an individual patient that the prescriber judges makes a significant difference¹⁴. If tesamorelin is prescribed for the approved indication, the approved product is the reference point.

Which one has the stronger evidence?

Tesamorelin, clearly, but only for what it was tested for. It has two phase 3 trials with more than 800 patients, 52-week data and a current label with measured rates of side effects^3,7. Its benefit is a reduction in visceral fat in HIV-associated lipodystrophy, not general fat loss, and the label says so. Sermorelin has a real approval history and pediatric efficacy data^1,10, but no current label, no large adult trials and no FDA-reviewed product on the market.

If you are prescribed either, keep your IGF-1, glucose and any side effects on the same timeline as your doses. Peptide Me lets you log injections and rotate abdominal sites, record lab results alongside them, and export the history for your appointment. For general technique, see how to inject peptides, and for the evidence framework across compounds, are peptides safe?

Disclaimer: this guide summarises FDA records, prescribing information and published trials and is not medical advice. Both drugs are prescription-only. Whether either is appropriate for you is a decision for you and your prescriber.

FAQ

References

Primary sources — PubMed / NEJM / The Lancet.

1. U.S. Food and Drug Administration. Determination That GEREF (Sermorelin Acetate) Injection, 0.5 Milligrams Base/Vial and 1.0 Milligrams Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 Milligrams Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness. Federal Register. 2013;78(42):14095-14096. https://www.govinfo.gov/content/pkg/FR-2013-03-04/html/2013-04827.htm
2. U.S. Food and Drug Administration. Drugs@FDA: BLA 022505 (EGRIFTA, tesamorelin; original approval 10 November 2010) and NDA 019863 / NDA 020443 (GEREF, sermorelin acetate; discontinued). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process
3. DailyMed. EGRIFTA SV (tesamorelin) for injection, for subcutaneous use — Prescribing Information. Theratechnologies Inc. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224
4. DailyMed. EGRIFTA WR (tesamorelin) for injection, for subcutaneous use — Prescribing Information. Theratechnologies Inc. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75
5. Theratechnologies Inc. Theratechnologies Receives FDA Approval for EGRIFTA WR (Tesamorelin F8) to Treat Excess Visceral Abdominal Fat in Adults with HIV and Lipodystrophy. Press release, 25 March 2025. https://www.globenewswire.com/news-release/2025/03/25/3049233/0/en/Theratechnologies-Receives-FDA-Approval-for-EGRIFTA-WR-Tesamorelin-F8-to-Treat-Excess-Visceral-Abdominal-Fat-in-Adults-with-HIV-and-Lipodystrophy.html
6. Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-2370. https://pubmed.ncbi.nlm.nih.gov/18057338/
7. Falutz J, Mamputu JC, Potvin D, et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010;95(9):4291-4304. https://pubmed.ncbi.nlm.nih.gov/20554713/
8. Stanley TL, Feldpausch MN, Oh J, et al. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014;312(4):380-389. https://pmc.ncbi.nlm.nih.gov/articles/PMC4363137/
9. Stanley TL, Fourman LT, Feldpausch MN, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019;6(12):e821-e830. https://pmc.ncbi.nlm.nih.gov/articles/PMC6981288/
10. Thorner M, Rochiccioli P, Colle M, et al. Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group. J Clin Endocrinol Metab. 1996;81(3):1189-1196. https://pubmed.ncbi.nlm.nih.gov/8772599/
11. Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs. 1999;12(2):139-157. https://pubmed.ncbi.nlm.nih.gov/18031173/
12. Vittone J, Blackman MR, Busby-Whitehead J, et al. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. 1997;46(1):89-96. https://pubmed.ncbi.nlm.nih.gov/9005976/
13. Baker LD, Barsness SM, Borson S, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Arch Neurol. 2012;69(11):1420-1429. https://pmc.ncbi.nlm.nih.gov/articles/PMC3764914/
14. 21 U.S.C. § 353a — Pharmacy compounding (section 503A of the Federal Food, Drug, and Cosmetic Act). Legal Information Institute, Cornell Law School. https://www.law.cornell.edu/uscode/text/21/353a