# Compare the Four Peptides — Peptides Foundation

> Side-by-side comparison of tesamorelin, semaglutide, thymosin alpha-1, and PT-141: drug class, studied use, evidence quality, regulatory status, and WADA status.

A structured side-by-side look at what each compound is, what it has been studied for, how strong that evidence is, and where it stands regulatorily.

## The short version

The four peptides on this desk share one frame — they have more clinical data than most — but their mechanisms, evidence quality, approved indications, and risk profiles are quite different. This table is designed to surface those differences quickly, not to imply the compounds are interchangeable or comparable in their applications. Read each compound page for the full picture.

## Comparison table

| | **Tesamorelin** | **Semaglutide** | **Thymosin Alpha-1** | **PT-141** |
|---|---|---|---|---|
| **Drug class** | GHRH analogue (GHRH-R agonist) | GLP-1 receptor agonist (incretin mimetic) | Thymic immunomodulatory peptide | Melanocortin receptor agonist (MC3R/MC4R) |
| **Primary study area** | Visceral fat, GH/IGF-1 axis | Metabolic disease (T2D, obesity), cardiovascular, kidney | Immune restoration, viral hepatitis, sepsis | Sexual desire (central) |
| **Mechanism** | Stimulates pituitary GH secretion → visceral lipolysis | Mimics GLP-1: insulin potentiation, glucagon suppression, central appetite reduction | TLR2/TLR9 signaling on dendritic cells → T-cell maturation; dual effector/regulatory immune effect | Central MC4R/MC3R agonism in hypothalamic/limbic sexual desire circuits |
| **Largest controlled human trial** | Meta-analysis of 5 RCTs in HIV lipodystrophy (n≈870 total) [1] | SELECT cardiovascular outcomes trial (n=17,604) [10] | TESTS sepsis trial (n=1,106) [13] — **null result** | Two phase-3 RECONNECT trials (n=1,267) [20] |
| **Evidence maturity** | Moderate — strong in its licensed population, limited outside it | High — multiple large pre-registered RCTs with hard endpoints | Moderate-low — large trial base, high heterogeneity, recent null phase-3 | Moderate — phase-3 data in specific approved indication; off-label data limited |
| **FDA status** | Approved (HIV-associated lipodystrophy, 2010) | Approved (T2D, obesity, CV risk, MASH) | Not approved (available investigationally) | Approved (HSDD in premenopausal women, 2019) |
| **Off-label use common in research communities?** | Yes — general visceral-fat reduction, anti-aging, cognitive | Yes — weight management outside approved populations | Yes — immune support generally | Yes — sexual enhancement in men and postmenopausal women |
| **WADA status** | Prohibited (S2: GHRH analogue, in- and out-of-competition) | Not specifically prohibited (verify current list) | Not specifically listed; immunomodulatory peptides in regulatory grey area | Non-approved substance framing (S0) |
| **Key safety concern** | IGF-1 elevation; visceral fat reaccumulates on discontinuation | Nausea (~1/3 of users); biliary disease; weight regain on stopping | Mild injection-site reactions; null large sepsis RCT tempers expectations | Nausea (~40%); transient BP increase; hyperpigmentation with frequent dosing |

## Reading the evidence-maturity column

The 'evidence maturity' column deserves explanation because it carries the most interpretive weight.

**Semaglutide** is rated high because it has multiple, independent, large, pre-registered RCTs with hard primary endpoints — cardiovascular death, kidney failure, confirmed weight change measured prospectively. Those are the gold standard and the trials met them.

**Tesamorelin** is rated moderate. Its RCTs are well-designed and consistent, but they were all conducted in the same narrow population (HIV-positive adults on antiretroviral therapy), limiting generalizability without further study.

**Thymosin alpha-1** is moderate-low not because the literature is thin — it spans four decades — but because the highest-quality trial in the best-studied acute indication came back null [13], and much of the remaining literature carries significant risk of bias.

**PT-141** is moderate. The phase-3 RECONNECT trials are properly controlled and replicated in two identical studies [20], but the approved indication is narrow, the effect sizes are modest, and the off-label evidence base is not at the same standard.

Evidence maturity is not the same as benefit. A compound with mature, high-quality evidence of moderate benefit (semaglutide) may be more useful in practice than one with thin evidence of a spectacular claimed effect.

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An exacting literature digest: what the controlled trials actually found, weighed against what they didn't, and nothing added to fill the gap.