EVIDENCE MAP
Five Compounds, One Spectrum
Where they converge, where they diverge, and — most importantly — how far the evidence behind each one actually reaches.
The short version
These five compounds are often discussed in the same breath, but they do not occupy the same place in the evidence hierarchy. Semaglutide and tirzepatide are FDA-approved drugs with multiple large RCTs behind them. Tesamorelin is approved, but only for one narrow HIV indication. Retatrutide is deep in Phase 3 trials but has no regulatory approval. BPC-157 is preclinical — animal models and a tiny handful of human pilots, with no approved indication anywhere.
The table below lines them up on the dimensions that matter when reading any research compound: what it targets, what stage its evidence is at, what regulators have concluded, and what the key caution is. None of these is presented with a human dose.
The evidence matrix
| Compound | Drug class | Primary research area | Evidence stage | Regulatory status | WADA | Key caution |
|---|---|---|---|---|---|---|
| Semaglutide | GLP-1 receptor agonist | Weight, T2D, CVD, CKD | Large Phase 3 RCTs (up to n=17,604) | FDA-approved (multiple indications) | Not prohibited | GI intolerance during dose escalation; retinopathy risk with rapid glycemic correction [5][7] |
| Tirzepatide | Dual GIP/GLP-1 agonist | Weight, T2D | Large Phase 3 RCTs (up to n=2,539) | FDA-approved (T2D; obesity; sleep apnea) | Not prohibited | GI intolerance; gallbladder/biliary disease signal [9][10] |
| Tesamorelin | GHRH analogue | HIV-lipodystrophy; visceral fat; hepatic fat | Phase 3 RCTs in HIV populations | FDA-approved for HIV lipodystrophy ONLY; all other use off-label | Prohibited S2 | Off-label use is investigational; VAT reaccumulates on stopping [12][16] |
| Retatrutide | Triple GIP/GLP-1/glucagon agonist | Weight, T2D, MASLD | Phase 2 complete; Phase 3 ongoing | Investigational — no approval anywhere (as of 2026) | Not currently prohibited | Unapproved; dose-dependent heart-rate increase; unverified gray-market material [17][20] |
| BPC-157 | Cytoprotective pentadecapeptide | Tissue repair, angiogenesis, gut | Preclinical (animal); 3 tiny human pilots | Not approved anywhere | Prohibited S0 | Single-lab preclinical evidence; only 3 human pilots; no large RCTs [22][23] |
Mechanism and target
The five compounds act through entirely different mechanisms. Semaglutide is a GLP-1 receptor agonist — it mimics the incretin hormone GLP-1, driving glucose-dependent insulin secretion, glucagon suppression, gastric slowing, and, centrally, appetite suppression [6]. Tirzepatide adds a second receptor to that picture: by agonizing the GIP receptor alongside GLP-1R, it produces larger glucose and weight effects than selective GLP-1 agonism alone [11].
Tesamorelin works upstream of the GH/IGF-1 axis entirely: it binds the GHRH receptor on pituitary cells, triggering the body's own pulsatile growth hormone release, which then drives lipolysis preferentially in visceral fat [15]. Because it amplifies endogenous GH rather than supplying exogenous GH, its metabolic and safety profile differs from recombinant growth hormone.
Retatrutide extends the dual-agonist principle to three receptors — GIP, GLP-1, and glucagon. The glucagon arm adds energy expenditure and lipid mobilization, which is the proposed mechanism behind its outsized weight-loss figures in Phase 2 [17][18]. BPC-157 operates through a different system entirely: animal-model evidence ties its repair effects to angiogenesis via the VEGFR2/Akt/eNOS pathway, cell-migration signaling, and the modulation of nitric-oxide systems [25].
Evidence base: what has been studied in humans
Semaglutide has the deepest human record. The SELECT trial enrolled 17,604 adults with established cardiovascular disease and overweight or obesity and found a 20% relative risk reduction in major adverse cardiovascular events [3]. The FLOW trial enrolled 3,533 people with type 2 diabetes plus chronic kidney disease and found a 24% lower risk of major kidney-disease events [2]. These are hard-outcome trials in high-risk populations.
Tirzepatide's Phase 2 and 3 program is comparable in scale: SURMOUNT-1 enrolled 2,539 adults and showed up to -20.9% mean body-weight change at 15 mg [10]; SURPASS-2 directly compared it to semaglutide in 1,879 people with type 2 diabetes and showed superiority [11]; SURMOUNT-5 (n=751) was a head-to-head comparison in obesity and found tirzepatide produced -20.2% versus -13.7% weight loss [1].
Tesamorelin's pivotal trials were in HIV-positive adults on antiretroviral therapy — a specific, narrow population. A 52-week program showed sustained -18% visceral fat reduction; a JAMA RCT (n=50) confirmed visceral-fat and hepatic-fat effects [14][16].
Retatrutide's Phase 2 obesity trial enrolled 338 adults and showed -24.2% body weight at 12 mg versus -2.1% with placebo [20]. A Phase 2 type 2 diabetes trial in 281 adults showed -16.94% weight at 36 weeks [21]. Phase 3 is running but unreported.
BPC-157's human file is genuinely small: a 2025 narrative review concluded that only three pilot studies have examined BPC-157 in humans, that rigorous large-scale trials are lacking, and that it should be treated as investigational [23]. A 2025 safety pilot gave intravenous BPC-157 to two healthy adults — the n is literally two [22].
Regulatory and WADA status
Semaglutide and tirzepatide are FDA-approved prescription medicines for multiple metabolic indications. Neither is currently prohibited by WADA, though athletes should verify current status independently.
Tesamorelin is FDA-approved specifically for HIV-associated lipodystrophy — that approval is narrow and real. Outside that indication, tesamorelin has no approved human use. It is prohibited in sport under WADA category S2 (peptide hormones, growth factors, related substances and mimetics), in- and out-of-competition.
Retatrutide has no regulatory approval anywhere as of mid-2026. It is investigational, studied exclusively under clinical-trial conditions. Products sold through gray-market research channels are unverified in identity and purity.
BPC-157 is not approved as a drug anywhere. It was placed by the FDA in 2023 in a category of substances not eligible for pharmacy compounding under 503A, pending further evaluation. It is prohibited in sport at all times by WADA under the S0 non-approved-substances category.
The key caution for each compound
For semaglutide: gastrointestinal intolerance is the dominant adverse effect profile, concentrated during dose escalation, and is the primary driver of discontinuation. An important signal from SUSTAIN-6 showed significantly higher rates of diabetic-retinopathy complications (HR 1.76) in patients with pre-existing retinopathy undergoing rapid glycemic correction [7]. Substantial weight regain follows discontinuation [4].
For tirzepatide: the same GI intolerance profile applies, and the composite gallbladder/biliary disease signal in a meta-analysis (RR 1.97) is the most consistently demonstrated safety concern beyond GI effects [9].
For tesamorelin: the narrow indication is the defining caution. The compound works for what it was approved for — visceral fat reduction in HIV lipodystrophy — but efficacy in non-HIV populations rests on a mechanistically plausible but unproven extrapolation, and VAT reaccumulates within weeks of stopping [16].
For retatrutide: being unapproved is the foundational caution. Dose-dependent heart-rate increases peaked around 24 weeks in Phase 2 [20], long-term cardiovascular outcomes data do not yet exist, and material obtained outside clinical trials cannot be verified for identity or purity.
For BPC-157: the body of evidence is overwhelmingly from a single research group's rodent work, independent replication is limited, only three human pilots exist, and the absence of long-term human safety data means the risk profile is genuinely unknown [23].