The Peptide Craze Critique: What Topol Got Right and Wrong
Peptide Regulation & FDA
15 peptides reviewed
In July 2025, cardiologist Eric Topol reviewed 15 injectable peptides used without FDA approval, concluding that 'the peptide craze is unfounded.'
Topol, Ground Truths, July 2025
Topol, Ground Truths, July 2025
View as imageIn July 2025, Eric Topol published "The Peptide Craze" on his Ground Truths Substack, reviewing 15 injectable peptides being used without FDA approval or off-label. His central conclusion: "there is no evidence from randomized trials in humans that any of these peptides provide the benefits that are advocated." He called the peptide craze "unfounded." As a cardiologist, editor-in-chief of Medscape, and one of the most influential voices in evidence-based medicine, Topol's critique carried weight. And much of it was right. But some of it missed important context. Here is a point-by-point analysis, measured against what the published literature actually shows. For regulatory background, see BPC-157 and the FDA: the Category 2 classification explained.
Key Takeaways
- Topol is correct that no large, placebo-controlled randomized trial has been completed for any non-FDA-approved injectable peptide, including BPC-157, TB-500, or CJC-1295
- The BPC-157 literature does contain over 100 animal studies showing tissue-protective effects, but only two small human pilot studies have been published, both by the same research group (Lee et al., 2024; Lee et al., 2025)
- Topol grouped peptides with wildly different evidence bases together, from thymosin alpha-1 (approved in multiple countries, dozens of clinical trials) to Dihexa (essentially zero human data)
- Ipamorelin has a published phase 2 randomized controlled trial in 117 surgical patients showing safety and tolerability, though efficacy endpoints were not met (Beck et al., 2014)
- Topol's comparison to GLP-1 drugs sets an impossibly high bar; GLP-1 agonists had 20 years and billions of dollars of pharma investment behind their evidence base
- Quality and purity concerns for compounding pharmacy peptides are legitimate; regulatory standards for peptide impurities remain limited even in the EU (Colalto, 2024)
What Topol Got Right
The Evidence Gap Is Real
Topol's core claim is accurate: there are no large, well-powered, placebo-controlled randomized trials for any of the non-FDA-approved peptides being sold through wellness clinics and compounding pharmacies. Not for BPC-157. Not for TB-500. Not for CJC-1295, ipamorelin, epithalon, or MOTS-c.
The BPC-157 literature, which is the largest among the non-approved peptides, consists primarily of rodent studies. Gwyer and colleagues reviewed the evidence in 2019 and found "consistently positive and prompt healing effects for various injury types" in animal models, but noted that "the efficacy of BPC 157 is yet to be confirmed in humans" and that "only a handful of research groups have performed in-depth studies regarding this peptide."[1]
That assessment remains essentially unchanged. The total human BPC-157 dataset consists of two small pilot studies by Edwin Lee and colleagues: a 2024 study of intravesical BPC-157 injection in 12 women with interstitial cystitis, reporting symptom resolution in 10 of 12 patients,[2] and a 2025 safety study of intravenous BPC-157 in 2 adults showing no adverse effects on tested biomarkers.[3] Neither study was blinded, neither had a control group, and both had tiny sample sizes. For more on the limits of BPC-157 research, we have a dedicated analysis.
Topol is right to flag this as a problem. People are injecting compounds into their bodies based on animal data and testimonials. That is a legitimate concern.
Purity and Contamination Risks Are Legitimate
Topol warned that "there is no way to know about the right dose, purity, potential contaminants, and the impact of long-term use in people." This is not alarmism. Colalto published a regulatory perspective in 2024 noting that quality and safety guidelines specific to peptides are limited, and that the analytical investigation of peptide-related impurities cannot follow the same approach used for small molecule drugs. Peptides can have hazardous interactions with biological systems that fall outside traditional toxicology frameworks.[5]
Compounding pharmacies operate under different regulatory frameworks than pharmaceutical manufacturers. 503A pharmacies compound on a per-patient basis with a prescription; 503B outsourcing facilities can produce larger batches but face less rigorous oversight than FDA-approved drug manufacturers. The peptide a patient receives from a compounding pharmacy may not be identical in purity or potency to the peptide used in published research. Rastogi and colleagues noted in 2019 that a lack of harmonization in quality specifications for peptide therapeutics across major pharmacopoeias creates inconsistency in standards.[6]
The Influencer Pipeline Is Problematic
Topol identified Gwyneth Paltrow, Joe Rogan, RFK Jr., and Gary Brecka as drivers of peptide demand and noted the irony of individuals who reject rigorously tested vaccines while embracing untested peptide injections. This observation stands on its own merits. When peptide education comes from social media influencers rather than clinical evidence, misinformation scales.
What Topol Got Wrong (or Oversimplified)
Lumping All Peptides Together
Topol's article reviewed 15 peptides as a group, but their evidence bases vary enormously. Thymosin alpha-1 is approved as a prescription drug (Zadaxin) in over 30 countries for chronic hepatitis B and as an immune adjunct during chemotherapy. Simonova and colleagues reviewed its established mechanisms in 2025, noting documented effects on T-cell maturation, dendritic cell function, and immune surveillance that have been validated in clinical settings over decades.[7] Its reclassification back to Category 1 for compounding reflects this evidence history.
At the other extreme, Dihexa has essentially no published human data. Treating thymosin alpha-1 and Dihexa as equivalent in evidence quality is misleading. A more useful analysis would have tiered the peptides by evidence strength, acknowledging that some have meaningful clinical data while others have none.
Similarly, the 14 peptides moving back to Category 1 have different regulatory histories and evidence profiles. Grouping them together obscures rather than illuminates.
Setting an Impossible Evidence Standard
Topol compared the peptide evidence base to GLP-1 receptor agonists, which he noted had "large, placebo-controlled, randomized trials" with "rigorous" testing over twenty years since the first FDA approval in 2005. This comparison is technically valid and practically meaningless.
GLP-1 drugs had billions of dollars in pharmaceutical industry investment because they addressed a massive market (type 2 diabetes, then obesity). Novo Nordisk's market capitalization grew to over $400 billion on the back of semaglutide. No peptide being sold through compounding pharmacies has this kind of commercial incentive behind it. BPC-157, for example, cannot be patented in its native sequence, which means no pharmaceutical company will fund a $50 million phase III trial for it because there is no way to recoup the investment through exclusivity.
This is not an excuse. It is an explanation. The absence of large trials does not mean the peptides are ineffective; it means the economic model for proving efficacy through the standard regulatory pathway does not exist for most of them. This structural problem in drug development deserves acknowledgment, not silence.
Ignoring What the Animal Data Actually Shows
Topol characterized the peptide evidence base as essentially nonexistent. This is true for human randomized trials. It is not true for the preclinical literature. BPC-157, for example, has over 100 published studies showing tissue-protective effects across gastric ulcers, tendon healing, bone fracture repair, muscle injury, nerve damage, and vascular dysfunction in rodent models.[1] The consistency of these findings across multiple tissue types and injury models is not typical of a compound with no biological activity. Read more about what the BPC-157 research actually shows.
Animal studies do not prove human efficacy. Many compounds that work in mice fail in humans. But dismissing 100+ consistent preclinical studies as irrelevant is not evidence-based medicine either. Evidence exists on a spectrum, and the honest assessment is: BPC-157 has strong preclinical evidence, minimal human evidence, and a biological plausibility gap that can only be closed by proper clinical trials.
Ipamorelin offers a useful counter-example. Beck and colleagues published a phase 2 randomized, double-blind, placebo-controlled trial of ipamorelin in 117 patients undergoing bowel resection in 2014. The trial showed that ipamorelin 0.03 mg/kg twice daily for up to 7 days was "well tolerated" with no significant safety concerns. The key efficacy endpoint (time to first tolerated meal) trended in favor of ipamorelin (25.3 vs. 32.6 hours) but did not reach statistical significance (p = 0.15).[4] This is not a home run, but it is a published human RCT that Topol's blanket dismissal overlooks.
Overlooking the Regulatory Context
Topol published his article in July 2025, months before the FDA reclassification of certain peptides from Category 2 back to Category 1, which restored legal compounding access. The regulatory context matters because it shapes what kind of evidence can be generated. When the FDA placed peptides in Category 2 (effectively banning compounding), it also removed the clinical context in which observational data and practice-based evidence could accumulate. The legal challenge that forced the FDA's hand on peptide restrictions was partly about preserving this pathway.
Category 1 status does not mean FDA approval. What reclassification does not mean is an important distinction. But the regulatory framework determines whether clinical data can be generated within the healthcare system or whether all use is driven underground to unregulated sources, which is worse for patient safety.
Where Topol's Analysis Should Land
The honest position on the peptide craze sits between Topol's blanket dismissal and the influencer community's uncritical enthusiasm:
The evidence gaps are real and serious. No one should inject any substance without understanding that the human evidence base for most non-approved peptides ranges from minimal to nonexistent. This is a fact.
The animal data is not nothing. Dismissing consistent preclinical findings across dozens of studies and multiple research groups is not intellectually honest. The appropriate response is to demand human trials, not to pretend the preclinical data does not exist.
The quality problem is solvable. Better regulatory frameworks for compounding pharmacies, standardized analytical methods for peptide purity, and clear labeling requirements would address many of Topol's legitimate safety concerns without banning access entirely.
Not all peptides are created equal. Thymosin alpha-1 with decades of clinical use in 30+ countries does not belong in the same evidence category as compounds with zero published human data. Any serious analysis must differentiate.
The economic model matters. The absence of large RCTs for unpatentable peptides is a market failure, not a scientific verdict. Acknowledging this does not weaken the call for evidence; it makes the call more honest about why the evidence does not yet exist.
Topol concluded that "the peptide craze is unfounded." A more precise conclusion would be: the peptide craze outpaces its evidence base. That distinction matters.
The Bottom Line
Eric Topol's July 2025 critique of the peptide craze correctly identified the central evidence problem: no large randomized controlled trials exist for non-FDA-approved injectable peptides. His concerns about purity, contamination, and influencer-driven demand are also warranted. But his analysis grouped peptides with vastly different evidence bases together, set a comparison standard (GLP-1 drugs) that ignores the economics of drug development for unpatentable compounds, and dismissed consistent preclinical data as irrelevant. The honest assessment is that the peptide craze outpaces its evidence, not that the evidence is absent.