Sermorelin vs. Tesamorelin: GHRH Analogs

Both sermorelin and tesamorelin are synthetic versions of growth hormone-releasing hormone (GHRH), the 44-amino-acid signal peptide that tells the pituitary gland to secrete growth hormone. Both bind the same receptor. Both trigger the same downstream cascade. Yet the two peptides were built for different problems, approved under different circumstances, and occupy different corners of clinical medicine today.

This article breaks down the science behind each molecule — what it is, how it works, where the evidence stands, and where the two diverge.

The Shared Starting Point: How GHRH Works

Before comparing these peptides head-to-head, it helps to understand the system they both tap into.

Your hypothalamus produces GHRH in pulses, mostly during sleep and exercise. That GHRH travels a short distance to the anterior pituitary, locks onto GHRH receptors on somatotroph cells, and triggers a burst of growth hormone (GH) into the bloodstream. GH then acts on tissues throughout the body — stimulating the liver to produce IGF-1, driving lipolysis in fat cells, and supporting protein synthesis in muscle.

The system self-regulates. When GH and IGF-1 levels climb high enough, somatostatin — the hypothalamic brake pedal — suppresses further GHRH signaling. This negative feedback loop keeps GH output within a physiological range. It is also why GH secretion declines with age: GHRH output drops, somatostatin tone increases, and the pituitary gradually produces less GH per pulse. By the time someone reaches 60, daily GH secretion may be a fraction of what it was at 25.

Both sermorelin and tesamorelin work by mimicking GHRH at that same receptor. They amplify the existing signal rather than replacing it. They stimulate GH release while preserving the somatostatin feedback system — meaning the pituitary can still "say no" when levels get too high. That built-in safety margin is what separates GHRH analogs from direct GH injections, which bypass the feedback loop entirely.

That basic pharmacological similarity is where the two peptides' stories begin to diverge.

Sermorelin: The Minimal Fragment

Structure and Pharmacology

Sermorelin is GHRH(1-29)NH2 — the first 29 amino acids of the native 44-amino-acid GHRH molecule, with an amidated C-terminus. Researchers in the 1980s discovered that this truncated fragment was the shortest sequence that could fully activate the GHRH receptor. The remaining 15 amino acids at the C-terminal end of native GHRH turned out to be biologically dispensable for receptor binding and activation, though they do contribute to the native molecule's stability in plasma.

The peptide has a molecular weight of about 3,358 daltons. It is administered by subcutaneous injection, typically at bedtime to coincide with the natural nocturnal GH surge. Standard doses in clinical use range from 200 to 500 mcg per day.

Sermorelin's main pharmacokinetic limitation is its short half-life. After subcutaneous injection, it reaches peak plasma concentrations within 5 to 20 minutes and clears with a half-life of roughly 10 to 12 minutes. Mean absolute bioavailability after subcutaneous dosing is only about 6%. The peptide degrades rapidly in plasma, largely through cleavage by dipeptidyl peptidase IV (DPP-IV).

Despite that brevity, a single injection can provoke a GH pulse lasting two to three hours, with peak GH levels typically appearing around 30 minutes post-dose. The downstream effect on IGF-1 — which has its own half-life of 12 to 24 hours — persists far longer than the peptide itself.

FDA History

Sermorelin has an unusual regulatory story. The FDA first approved it in 1990 as a diagnostic agent — an injectable test to evaluate whether a child's pituitary could still produce GH. A second approval followed in 1997 for therapeutic use: treating idiopathic growth hormone deficiency in children with growth failure.

Both approvals were held by EMD Serono under the brand name GEREF. In 2008, EMD Serono voluntarily discontinued the product — not because of safety problems, but because of manufacturing difficulties with the active ingredient. The FDA formally withdrew the NDAs in 2009, and in 2013, the agency published a determination confirming that GEREF was not withdrawn for reasons of safety or effectiveness.

That distinction matters. Because the withdrawal was commercial rather than safety-based, sermorelin remains available through compounding pharmacies. It was not placed on the FDA's Category 2 bulk drug substance list in 2023, unlike several other growth hormone secretagogues (ipamorelin, GHRP-2, GHRP-6, and CJC-1295 among them) that were effectively banned from compounding.

Clinical Evidence

The strongest evidence for sermorelin comes from pediatric growth hormone deficiency. A 1996 study showed that daily sermorelin injections increased growth velocity in 74% of children within six months. Preliminary data from longer follow-up suggested sustained efficacy at 36 months.

In adults, the data is thinner. Several small studies and observational reports have found that sermorelin injections raise GH and IGF-1 levels, with associated improvements in body composition — more lean mass, less fat — and self-reported improvements in sleep quality. In elderly men, 2 mg daily for two weeks increased IGF-1 by approximately 25%, bringing levels closer to those seen in younger untreated men. That IGF-1 elevation persisted for two weeks after discontinuation.

But large, randomized, controlled trials in healthy adults are absent. The off-label use of sermorelin for anti-aging, body composition, and sleep remains driven more by clinical observation and pharmacological reasoning than by the kind of rigorous evidence that supported its pediatric indication.

Tesamorelin: The Engineered Upgrade

Structure and Pharmacology

Where sermorelin truncated GHRH down to the minimum active fragment, tesamorelin took the opposite approach. It preserves all 44 amino acids of native GHRH and adds a chemical modification: a trans-3-hexenoic acid group conjugated to the N-terminal tyrosine residue.

That modification gives the peptide its formal name — N-(trans-3-hexenoyl)-[Tyr1]hGRF(1-44)NH2 — and a molecular weight of about 5,136 daltons (free base). The hexenoyl group was specifically engineered to shield the peptide from DPP-IV, the enzyme that chews through unmodified GHRH and sermorelin within minutes.

Despite this structural protection, tesamorelin still clears quickly. The FDA label reports a mean elimination half-life of approximately 26 minutes after subcutaneous injection — longer than sermorelin, but still measured in minutes rather than hours. The approved dose is 2 mg once daily by subcutaneous injection.

The real difference is in potency. In healthy middle-aged men, two weeks of tesamorelin at 2 mg daily increased total GH output (measured by area under the curve) by 69%, average GH pulse area by 55%, and IGF-1 by 122%. Those are substantially larger responses than what sermorelin produces at typical clinical doses.

FDA Approval

Tesamorelin holds a distinction that sermorelin never achieved: it remains FDA-approved. In 2010, the FDA approved Egrifta (tesamorelin for injection), developed by Theratechnologies, as the first and only medication indicated for reducing excess abdominal fat in HIV-infected adults with lipodystrophy.

HIV-associated lipodystrophy is a side effect of antiretroviral therapy in which visceral fat accumulates abnormally — particularly around the abdomen and internal organs — while subcutaneous fat wastes away in the face and limbs. The condition raises cardiovascular risk and significantly affects quality of life.

The approval rested on two Phase III trials (LIPO-010 and CTR-1011) enrolling 816 HIV-positive adults with clinically defined lipodystrophy. Each trial consisted of a 26-week main phase followed by a 26-week extension. In these multicenter, randomized, double-blind, placebo-controlled studies, tesamorelin 2 mg daily reduced visceral adipose tissue (VAT) by 15 to 20% over 26 weeks, as measured by CT scan at the L4-L5 level. The minimum clinically meaningful reduction had been set in advance at 8%; tesamorelin cleared that bar comfortably in both studies.

The reductions were selective — subcutaneous fat was largely unaffected — which is a noteworthy detail. Rather than producing generalized fat loss, tesamorelin appeared to target the deep, metabolically active visceral fat surrounding abdominal organs. Patients also reported improvements in belly image distortion, an outcome that matters in a population where visible lipodystrophy carries psychological and social weight.

In 2025, Theratechnologies received FDA approval for a new formulation called EGRIFTA WR (tesamorelin F8), which requires only weekly reconstitution and uses less than half the injection volume of the previous version. The active molecule is unchanged; the reformulation was designed to reduce patient burden and improve adherence.

Beyond HIV: The NAFLD Connection

Some of the most compelling tesamorelin research has nothing to do with body fat distribution. In a randomized, double-blind, multicenter trial published in The Lancet HIV in 2019, researchers tested tesamorelin against placebo in 61 HIV-positive patients with nonalcoholic fatty liver disease (NAFLD).

After 12 months, the tesamorelin group showed a 37% relative reduction in hepatic fat fraction compared to baseline. Thirty-five percent of tesamorelin-treated patients dropped below the 5% liver fat threshold — compared to just 4% on placebo. Most striking was the effect on fibrosis: only 10.5% of tesamorelin patients showed fibrosis progression versus 37.5% on placebo.

These findings made tesamorelin the first agent shown to both reduce liver fat and slow fibrosis progression in HIV-associated NAFLD. A subsequent study presented at IDWeek 2023 confirmed that tesamorelin also reduced liver fat in patients on integrase strand transfer inhibitor (INSTI)-based antiretroviral regimens, a population at particular metabolic risk. For a deeper look at these tesamorelin trials, our dedicated research review covers the data in detail.

Theratechnologies has announced plans to develop tesamorelin for NASH (now called MASH) in the general, non-HIV population, with the FDA greenlighting progression to Phase 3. Results from that broader trial have not yet been published.

Head-to-Head: Where They Differ

Molecular Design

Sermorelin is a minimalist — the smallest piece of GHRH that still works. Tesamorelin is an optimization — the full native sequence, chemically armored against enzymatic degradation. This difference in design philosophy translates directly into differences in potency, half-life, and clinical profile.

Potency and GH/IGF-1 Output

Tesamorelin produces a significantly larger GH and IGF-1 response at clinical doses. The 122% IGF-1 increase seen with tesamorelin dwarfs the 25% increase reported with sermorelin in elderly men. This is not surprising given that tesamorelin carries 15 additional amino acids, a protective chemical modification, and is dosed at 2 mg versus sermorelin's typical 200 to 500 mcg.

Whether more GH output is always better depends on the clinical goal. For targeted visceral fat reduction, the stronger signal matters. For general optimization — where the intent is to restore youthful GH pulsatility without pushing IGF-1 into ranges that raise concern — sermorelin's gentler profile may be an advantage.

Approved Indications

Tesamorelin is the only GHRH analog with a current FDA approval. Its approved use is narrow: reducing excess abdominal fat in HIV-associated lipodystrophy. Sermorelin's approvals for pediatric GH deficiency were withdrawn in 2009 when the manufacturer exited the market.

In practice, sermorelin is prescribed off-label through compounding pharmacies for a range of indications including age-related GH decline, body composition optimization, and sleep support. Tesamorelin sees both on-label use in HIV lipodystrophy and off-label use for visceral fat reduction and metabolic health in non-HIV populations.

Safety Profiles

Both peptides work through the GHRH receptor and preserve the somatostatin feedback loop, which limits the risk of supraphysiological GH excess — a meaningful safety advantage over direct GH injections. Comparing the two to exogenous HGH is a separate discussion covered in our peptide therapy vs. HGH guide.

Sermorelin has a mild side-effect profile in clinical use. The most commonly reported effects are injection-site reactions (redness, pain, swelling), occasional headache, and transient flushing. Because it produces a relatively modest IGF-1 increase and clears rapidly, long-term safety concerns are limited — though long-term controlled data in adults is sparse.

Tesamorelin has more robust safety data, drawn from its Phase III trials and extension studies. In 154 patients treated for up to 52 weeks, reductions in visceral fat persisted and no new adverse events emerged. The most common side effects were arthralgia, injection-site reactions, pain in extremities, peripheral edema, and myalgia.

The more significant tesamorelin safety signal involves glucose metabolism. In the clinical trials, patients receiving tesamorelin had a higher rate of developing diabetes (HbA1c reaching 6.5% or above) compared to placebo — 5% versus 1%, yielding a hazard ratio of 3.3. The FDA label carries a warning about glucose intolerance and recommends monitoring blood glucose during therapy. Other labeled warnings include fluid retention, hypersensitivity reactions, and a caution against use in patients with active malignancy, given that GH and IGF-1 can theoretically promote tumor growth.

Duration of Effect

One important caveat with tesamorelin: its effects on visceral fat do not persist after discontinuation. When patients stop treatment, visceral fat tends to reaccumulate. This makes tesamorelin a maintenance therapy rather than a cure — and raises cost-effectiveness questions that have been debated in pharmacoeconomic reviews.

Sermorelin's effects on GH pulsatility may have slightly more carry-over. Some data suggest that IGF-1 elevations persist for roughly two weeks after stopping treatment, though long-term rebound data is lacking.

Cost and Access

The economics of these two peptides sit at opposite ends of the spectrum.

Tesamorelin (Egrifta SV / Egrifta WR) is a specialty pharmaceutical dispensed through specialty pharmacies. Without insurance, retail costs run approximately $9,000 to $10,000 per month. Patient assistance programs can reduce this substantially — in some cases to under $100 per month — but out-of-pocket costs remain a barrier for many patients.

Sermorelin, available through compounding pharmacies, typically costs between $100 and $300 per month depending on the pharmacy and dose. The absence of a branded product means no insurance formulary placement, but the base cost is far lower.

How They Compare to Other GH Secretagogues

Sermorelin and tesamorelin are not the only peptides in this space. CJC-1295 — a GHRH analog with a drug affinity complex (DAC) that extends its half-life to days rather than minutes — represents another approach. Our CJC-1295 vs. sermorelin comparison covers that matchup in detail.

Growth hormone-releasing peptides (GHRPs) like ipamorelin, GHRP-2, and GHRP-6 work through a different receptor entirely — the ghrelin receptor — and can be combined with GHRH analogs for synergistic GH release. However, many of these peptides were placed on the FDA's Category 2 list in 2023, restricting their availability through compounding pharmacies. MK-677 (ibutamoren), an oral ghrelin receptor agonist, operates through the same pathway but is not a peptide.

Among the GHRH analogs specifically, tesamorelin stands alone as the only one with a current FDA approval and large-scale clinical trial data. Sermorelin occupies the position of longest clinical history and widest off-label use. CJC-1295 offers the most convenient dosing but the least regulatory clarity.

Who Uses Each Peptide — and Why

The clinical contexts for these two peptides have diverged significantly.

Tesamorelin is prescribed primarily for:

HIV-associated lipodystrophy (FDA-approved indication)
Visceral fat reduction in metabolically at-risk patients
Emerging investigation in NAFLD/NASH, where its liver fat and fibrosis data are strongest among GHRH analogs

Sermorelin is prescribed primarily for:

Age-related GH decline (off-label)
Body composition support — modest fat loss and lean mass preservation
Sleep quality improvement
General GH optimization in patients who prefer a physiological, lower-intensity approach

Neither peptide is a substitute for exogenous GH in patients with severe, confirmed growth hormone deficiency. And neither is approved or appropriate for athletic performance enhancement — both are prohibited in sport by WADA.

The Bottom Line

Sermorelin and tesamorelin are closer in origin than they are in application. They share a receptor, a mechanism, and a physiological logic. But sermorelin is a 29-amino-acid fragment with a 10-minute half-life, a withdrawn approval, and a quiet second life in compounding pharmacies. Tesamorelin is a 44-amino-acid engineered molecule with an active FDA indication, Phase III data in HIV lipodystrophy, and expanding research in liver disease.

If the question is which peptide has stronger evidence behind it, the answer is tesamorelin — and it is not close. Two large randomized controlled trials, an FDA approval, published NAFLD data in The Lancet HIV, and ongoing Phase 3 development in NASH give it a clinical evidence base that sermorelin cannot match.

If the question is which peptide offers a gentler, more accessible entry point into GHRH-based GH support, sermorelin holds that position — with a lower side-effect burden, lower cost, and a dosing profile that many clinicians find attractive for long-term optimization.

The choice between them is not a matter of which is "better" in the abstract. It depends on the clinical goal, the patient's metabolic profile, and — as with so many things in medicine — the quality of the conversation between patient and physician.

This article is for educational purposes only and does not constitute medical advice. Consult a qualified healthcare provider before starting any peptide therapy. PeptideJournal.org does not sell peptides or have financial relationships with peptide vendors.