How to Pick Your First Peptide and What to Add After That

You type "best peptides" into Google and get a wall of compounds that read like Wi-Fi passwords. BPC-157, GHK-Cu, TB-500, SS-31, MOTS-c. Every one of them has someone swearing it changed their life, and none of them come with instructions on where to start.

So people buy eight of them, run everything at once for a fortnight, feel nothing they can attribute to anything, and quit. The money is gone and they have learned precisely nothing, because when you change eight variables simultaneously you cannot tell which one moved the needle.

This article is about the fix, and the fix is boring: order. Dr Ashley Froese laid out a sequencing framework in a video called The Ultimate Peptide Roadmap, built around the idea that peptides are biological instructions, and instructions only work if the thing receiving them is in a state to act on them. Installing new software on a machine with a dead battery accomplishes nothing.

What follows is that roadmap, stage by stage, with an honest accounting of what the research actually supports at each step. Some of these compounds have real randomised trials behind them. Most do not. You should know which is which before you spend anything.

Why the order beats the selection

The usual failure is not picking a bad peptide. It is picking a reasonable peptide at a moment when your body cannot respond to it.

There is real physiology behind this, and it is worth understanding because it justifies the whole sequence. Obesity markedly suppresses growth hormone output. Pulse amplitude drops, pulse frequency drops, and the effect tracks with fasting insulin and insulin resistance. Hyperinsulinaemia, elevated leptin, and raised free fatty acids all push pituitary GH secretion down, and visceral obesity in particular is associated with low GH output.

Read that again with a stack in mind. If you are carrying significant visceral fat and you spend four hundred dollars on a growth hormone secretagogue, you are paying to shout at a receptor system that your own metabolic state is actively muffling. Lose the weight first and the same compound has a better environment to work in.

I want to be careful here, because this is a mechanistic argument rather than a proven one. Nobody has run a trial that randomised people to "fix metabolic health first" versus "don't" and then measured how well they responded to peptides afterwards. The physiology is well established. The sequencing conclusion drawn from it is reasonable inference, not demonstrated fact.

Rule one, pick one thing to fix first

Just one. Weight, energy, sleep and recovery, repair, or skin.

The framework uses a composite character to make this concrete: someone who is tired, overweight, sore in the joints, recovering badly, and unhappy with their skin and hair. Which is to say, most people who go looking for peptides in the first place. Nearly everyone presents with all five complaints at once, and the temptation is to attack all five at once.

Resist it, for two reasons. The obvious one is that you cannot attribute an effect when everything changes together. The less obvious one is that these complaints are not independent. Fixing the first often improves several of the others for free, which means you may never need to buy the compounds you were planning to buy for problems three and four.

Stage 1, start with the weight

If you have a meaningful amount of weight to lose, begin there. It is the intervention that improves the most other things at once, and it improves the ground conditions for everything you might add later.

Retatrutide is the heavy artillery. It is a triple agonist hitting GLP-1, GIP and glucagon receptors, and the glucagon arm is what distinguishes it from the drugs people already know. In the phase 2 obesity trial, 48 weeks produced dose-dependent weight loss of 8.7% at 1mg through to 24.2% at 12mg, against 2.1% on placebo (Jastreboff et al., 2023). A phase 2a trial in fatty liver disease cut liver fat by between 42.9% and 82.4% depending on dose, and 86% of the 12mg group brought liver fat back under 5% (Sanyal et al., 2024).

Those are serious numbers. They also come with serious gastrointestinal side effects, with nausea and diarrhoea affecting roughly a third of participants and frequently limiting the dose. And retatrutide is not approved. Not in Australia, not in the United States, not anywhere. Lilly has not yet filed.

The appetite suppression is real and well documented. The claim you will see repeated everywhere, that retatrutide raises the calories you burn at rest, is on thinner ice: that rests largely on animal pharmacology, not on a dedicated human metabolic study.

Tesamorelin attacks fat from a different direction, preferentially mobilising visceral and liver fat rather than subcutaneous. This is the one genuinely approved drug in this entire article, cleared in 2010 for visceral fat reduction in HIV-associated lipodystrophy on the back of a 26-week randomised trial in 412 patients (Falutz et al., 2007). A later trial confirmed it reduces liver fat and limits fibrosis progression (Stanley et al., 2019), and visceral fat reduction tracked with improvements in triglycerides, HDL and insulin resistance (Stanley et al., 2012).

Note the population though. Every one of those trials was in people with HIV-associated lipodystrophy. Using it as a lean bodybuilder is off-label and genuinely unstudied in that group. And because it works by stimulating growth hormone, whether that is appropriate for you is a conversation with a doctor, not a purchase decision.

MOTS-c sits here too, though I would frame it as a mitochondrial peptide that happens to help with weight rather than a weight loss drug. The pitch is that it promotes mitochondrial biogenesis and improves insulin sensitivity, which sets up the next stage while you are still working on this one.

The pitch is also almost entirely built on mice. There is no completed human trial of administered MOTS-c. The insulin sensitivity data comes from diet-induced obese mice (Kim et al., 2019). The frequently cited human finding shows only that your own MOTS-c rises about twelve-fold in muscle after exercise, which is an observation about endogenous physiology, not evidence that injecting it does anything (Reynolds et al., 2021). A first-in-human trial is registered but has not reported.

Stage 2, fix the energy

Say the weight is coming off, you are moving better, and you still wake up feeling like someone forgot to plug you in. Two places to look: mitochondria and sleep.

SS-31 is the interesting one, and it is almost universally described wrongly. It is not a mitochondrial booster. It binds cardiolipin in the inner mitochondrial membrane and stabilises cristae structure, making electron transport more efficient and reducing reactive oxygen species leakage. You are repairing the engine, not asking it for more horsepower.

It is also the only compound here besides tesamorelin with an approval attached: it was granted accelerated FDA approval in September 2025, sold as Forzinity, for improving muscle strength in Barth syndrome (Thompson et al., 2024). Barth syndrome affects roughly one in a million male births and involves a severe inherited defect in cardiolipin remodelling. That is the entire evidence base in humans.

Here's the catch, though. When the same compound was tested in dry age-related macular degeneration, the phase 2 trial missed its primary endpoints despite showing some structural signal. Mitochondrial protection in one disease does not automatically generalise to another, and it certainly does not automatically generalise to a healthy athlete who simply feels flat.

Running SS-31 alongside MOTS-c is a reasonable idea on paper, since one stabilises existing mitochondria and the other is claimed to build more. Just be clear that "reasonable on paper" is the whole of the case.

Then growth hormone signalling, and pick one GHRH

This is where most stacks go wrong, and the mistake is specific enough to name.

Tesamorelin, sermorelin and CJC-1295 are all GHRH analogues. They all bind the same receptor. Running two of them together does not give you two mechanisms, it gives you more molecules queuing for the same receptor that the first compound is already stimulating well past physiological levels. There is no human data showing benefit from stacking two GHRH analogues, and stacking tesamorelin with CJC-1295 is the version of this error I see most often. You are doubling the cost without doubling the IGF-1 response.

Ipamorelin is a different animal, and this is the distinction that makes the whole section make sense. It is a ghrelin receptor agonist working through GHS-R1a, a separate receptor using a separate intracellular pathway. Combining a GHRH analogue with a ghrelin-pathway agonist is genuinely synergistic, and unusually for this field it has been demonstrated in humans since 1990, when submaximal doses of both together produced peak growth hormone well above either alone (Bowers et al., 1990). The effect has been replicated in adults who responded to neither compound individually (Leal-Cerro et al., 1995), and the two pathways were confirmed to be pharmacologically distinct rather than converging (Chen et al., 1998).

So the rule is one GHRH, optionally plus a GHRP. Never two GHRHs.

Tesamorelin or sermorelin

Choose on goal. Tesamorelin if visceral fat is the target, since that is the indication it was approved for and the outcome it has been tested against. Sermorelin if sleep and recovery matter more.

One thing you should know before buying sermorelin, because the internet tends to gloss over it: it is not a currently approved drug. The branded product was voluntarily pulled from the US market in 2002 for commercial reasons rather than safety ones, and everything sold under that name today is compounded or grey market. That is a different risk profile from a regulated pharmaceutical, and worth going in with your eyes open.

Why ipamorelin gets used the way it does

Ipamorelin's selling point is selectivity. Older growth hormone releasing peptides pushed cortisol and prolactin up alongside growth hormone. Ipamorelin was the first characterised as releasing growth hormone without meaningfully moving either, initially in animals (Raun et al., 1998) and then in a placebo-controlled dose-escalation study in 40 healthy men, where cortisol and prolactin stayed flat across five dose levels (Gobburu et al., 1999). That is better human substantiation than most of this field manages.

The timing logic

GHRH analogues get taken at night, and that has a solid basis. The early-sleep growth hormone pulse accounts for most of your daily output in men, and it is GHRH-driven (Dimaraki et al., 2003). Dosing before bed rides a pulse your body is already producing.

Ipamorelin gets taken away from food, and that also has a basis, though a softer one. Elevated glucose blunts the growth hormone response to secretagogues, an effect attributed to glucose-driven somatostatin release and demonstrated in humans decades ago (Ghigo et al., 1992). The mechanism is real. How much it matters for a healthy person who ate a normal meal two hours ago, as opposed to someone on a hyperglycaemic clamp, has never been directly quantified. Treat "dose it fasted" as sensible rather than critical.

Stage 3, repair what still hurts

Weight down, energy back, sleeping properly, and the knee still complains every time you play. This is where BPC-157 and TB-500 enter, usually together, sometimes called the Wolverine blend.

The mental model is clean. BPC-157 acts as a spotlight, improving blood flow to damaged tissue and flagging it for attention, working through VEGFR2-driven angiogenesis. TB-500 organises the repair crew, sequestering actin and acting as a chemoattractant that pulls cells toward the injury to rebuild (Malinda et al., 1997), with its actin-binding domain driving angiogenesis (Philp et al., 2003). They complement each other, which is why they are sold as a pair.

One practical point that saves people real discomfort: these are systemic. You do not have to inject a sore shoulder in the shoulder. Once the compound is circulating it goes where healing is being signalled, so putting it somewhere with good blood flow makes more sense than jabbing a joint. The evidence for systemic action is preclinical rather than confirmed in humans, and it is stronger for TB-500 than for BPC-157, but the mechanism supports it.

Now the part the sales pages leave out. BPC-157 has no published human efficacy trials. A 2025 review found exactly three human pilot studies in existence, none placebo-controlled, and called for actual trials to be run (McGuire et al., 2025). The one recent human safety paper tested two people (Lee and Burgess, 2025). Everything else is rats.

BPC-157 is also explicitly banned in sport. It was added by name to the WADA prohibited list in 2022 under the non-approved substances category, prohibited at all times with no therapeutic use exemption available. If you are tested, this one ends your season.

TB-500 deserves a specific warning too. People cite phase 2 trial data to justify it, and those trials are real, but they used a pharmaceutical-grade full-length thymosin beta-4 developed by an actual company, not the truncated fragment sold in vials online. Those trials also did not fully clear their endpoints. The compound you can buy has no human trials of its own and frequently unverified identity.

Stage 4, calm the inflammation

If the joints are better but the skin is still flaring, or an immune response is running hotter than it should, KPV is the next lever.

KPV is the tail end of alpha-MSH, three amino acids long. Most people file it as a gut peptide, and the gut data is where the research is, but the more interesting property is general anti-inflammatory action through NF-kB and MAPK inhibition, which is why it gets used for skin and histamine-driven problems as well. The foundational work showed oral KPV reducing colitis severity and cytokine production in mice via the PepT1 transporter (Dalmasso et al., 2008).

In mice. There are no human trials of KPV for anything. Not for inflammatory bowel disease, not for skin. The mechanism is genuinely elegant and the rodent data is genuinely encouraging, and that is the entire case.

Stage 5, skin and hair

GHK-Cu is filed under skin peptide, which undersells it. It is a copper-binding tripeptide that acts on tissue remodelling more broadly, stimulating collagen synthesis, modulating matrix metalloproteinases and proteoglycans, and driving angiogenesis, with claims extending to wound healing and hair follicles (Pickart et al., 2012).

The evidence base here is better than most of this article, but it is pointed somewhere specific: it is topical and cosmetic. The human trials that exist studied creams, on wounds and post-laser skin, and not all of them were positive. There are no trials of injected GHK-Cu for systemic anti-aging, hair regrowth or tissue remodelling.

The copper is worth a thought too, since you are injecting a metal complex repeatedly. We covered the arithmetic on cumulative copper load from GLOW-type blends in a separate article on GLOW and copper, and it is not a trivial amount over an eight-week run.

The stacks you just built by accident

Work through the stages and you assemble two well-known blends without setting out to.

BPC-157 plus TB-500 plus GHK-Cu is GLOW. Add KPV to those three and you have KLOW. That is the entire difference between the two names, and we broke down what that fourth peptide changes in a GLOW versus KLOW comparison.

This is a useful thing to notice, because it works in reverse as a sanity check. If you find yourself buying a pre-mixed blend, ask which stage each component is for, and whether you actually have that problem. Buying KLOW when your only real complaint is a sore elbow means you are paying for three peptides to treat one issue.

The advanced shelf, and why you do not start there

Past this point sit the compounds people tend to hear about first and should reach for last.

Thymosin alpha-1 is for immune function, and it is the real thing: approved in more than thirty countries for chronic hepatitis B, with a phase 3 programme behind it and a pivotal trial showing a complete virological response of 40.6% against 9.4% in controls (Chien et al., 1998). Strong evidence, for an antiviral indication that has nothing to do with training.

Epitalon is the longevity pick, and it comes with a trap. The famous human data, a multi-year follow-up reporting reduced mortality in elderly subjects, used Epithalamin, a pineal gland extract. What is sold today is synthetic Epitalon, a different compound. The study was also unblinded, had no placebo arm, and has never been replicated outside the group that ran it.

Selank is the anxiolytic, and it is quietly the best-supported of the three. A randomised trial in 62 patients with generalised anxiety found it comparable to a benzodiazepine on standard anxiety scales without the sedation (Zozulya et al., 2008). Small, Russian-language, never independently replicated in the West, but a genuine controlled trial.

Dihexa gets mentioned for cognition and is the weakest thing on this page. No human trials at all, and worse, its foundational preclinical literature is compromised: one landmark paper carries an expression of concern and a follow-up was retracted.

Where this roadmap is thinner than it sounds

Here is the part the video does not cover, and it matters more than the sequencing.

The framework is sound. The order is defensible. But sequencing tells you nothing about whether the individual compounds work, and for most of them the honest answer is that nobody knows. Laid out plainly:

Four of twelve have meaningful human evidence, and three of those four earned it in a disease population you almost certainly do not belong to. That does not mean the rest do nothing. It means nobody has checked properly, and you are the experiment.

The other honest caveat is that a stepwise roadmap is a teaching device, not a law. You could reasonably start BPC-157 in stage one alongside a weight loss compound if a torn tendon is what actually bothers you. The stages exist to keep you from changing everything at once, not because your body processes them in that order.

Key takeaways

• Sequence beats selection. Most failed peptide experiments failed because too much changed at once, not because the compounds were wrong.
• Start with weight if you have meaningful weight to lose. Obesity suppresses growth hormone secretion, so unaddressed metabolic dysfunction blunts the response to anything GH-related you add later.
• Run one GHRH, never two. Tesamorelin, sermorelin and CJC-1295 all hit the same receptor. Pairing a GHRH with ipamorelin is different and genuinely synergistic, with human evidence going back to 1990.
• BPC-157 and TB-500 are systemic. Inject somewhere with good blood flow rather than into the painful joint.
• GLOW is BPC-157, TB-500 and GHK-Cu. KLOW is those three plus KPV.
• Leave the advanced shelf alone until the basics are handled, and know that dihexa has a retracted paper in its own preclinical chain.
• Most of these compounds have no human efficacy trials. Four of the twelve here have solid human data, mostly in disease populations. Budget your expectations accordingly.

---

References

1. Jastreboff, A. M., Kaplan, L. M., Frias, J. P., Wu, Q., Du, Y., Gurbuz, S., et al. (2023). Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. New England Journal of Medicine, 389(6), 514-526. PubMed
2. Sanyal, A. J., Kaplan, L. M., Frias, J. P., Brouwers, B., Wu, Q., Thomas, M. K., et al. (2024). Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine, 30, 2037-2048. PubMed
3. Falutz, J., Allas, S., Blot, K., Potvin, D., Kotler, D., Somero, M., et al. (2007). Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine, 357(23), 2359-2370. PubMed
4. Stanley, T. L., Fourman, L. T., Feldpausch, M. N., Purdy, J., Zheng, I., Pan, C. S., et al. (2019). Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV, 6(12), e821-e830. PubMed
5. Stanley, T. L., Feldpausch, M. N., Murphy, C. A., Grinspoon, S. K., & Makimura, H. (2012). Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clinical Infectious Diseases, 54(11), 1642-1651. PubMed
6. Kim, S. J., Miller, B., Mehta, H. H., Xiao, J., Wan, J., Arpawong, T. E., et al. (2019). The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity. Physiological Reports, 7(13), e14171. PubMed
7. Reynolds, J. C., Lai, R. W., Woodhead, J. S. T., Joly, J. H., Mitchell, C. J., Cameron-Smith, D., et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications, 12, 470. PubMed
8. Thompson, W. R., Manuel, R., Abbruscato, A., Carr, J., Campbell, J., Hornby, B., et al. (2024). Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genetics in Medicine, 26(7), 101138. PubMed
9. Bowers, C. Y., Reynolds, G. A., Durham, D., Barrera, C. M., Pezzoli, S. S., & Thorner, M. O. (1990). Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Journal of Clinical Endocrinology and Metabolism, 70(4), 975-982. PubMed
10. Leal-Cerro, A., Torres, E., Soto, A., Dios, E., Deghenghi, R., Arvat, E., et al. (1995). Growth hormone (GH) responses to the combined administration of GH-releasing hormone plus GH-releasing peptide 6 in adults with GH deficiency. European Journal of Endocrinology, 132(6), 712-715. PubMed
11. Chen, C., Wu, D., & Clarke, I. J. (1998). Effect of growth hormone-releasing peptide-2 (GHRP-2) and GH-releasing hormone on cAMP levels and GH release from cultured pituitary cells. Journal of Neuroendocrinology, 10(8), 577-583. PubMed
12. Raun, K., Hansen, B. S., Johansen, N. L., Thogersen, H., Madsen, K., Ankersen, M., & Andersen, P. H. (1998). Ipamorelin, the first selective growth hormone secretagogue. European Journal of Endocrinology, 139(5), 552-561. PubMed
13. Gobburu, J. V., Agerso, H., Jusko, W. J., & Ynddal, L. (1999). Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharmaceutical Research, 16(9), 1412-1416. PubMed
14. Dimaraki, E. V., Jaffe, C. A., Bowers, C. Y., Marbach, P., & Barkan, A. L. (2003). Pulsatile and nocturnal growth hormone secretions in men do not require periodic declines of somatostatin. American Journal of Physiology: Endocrinology and Metabolism, 285(1), E163-E170. PubMed
15. Ghigo, E., Arvat, E., Valente, F., Nicolosi, M., Boffano, G. M., Procopio, M., et al. (1992). Arginine abolishes the inhibitory effect of glucose on the growth hormone response to growth hormone-releasing hormone in man. Metabolism, 41(9), 1000-1003. PubMed
16. Malinda, K. M., Goldstein, A. L., & Kleinman, H. K. (1997). Thymosin beta 4 stimulates directional migration of human umbilical vein endothelial cells. FASEB Journal, 11(6), 474-481. PubMed
17. Philp, D., Huff, T., Gho, Y. S., Hannappel, E., & Kleinman, H. K. (2003). The actin binding site on thymosin beta4 promotes angiogenesis. FASEB Journal, 17(14), 2103-2105. PubMed
18. McGuire, F. P., Martinez, R., Lenz, A., Skinner, L., & Cushman, D. M. (2025). Regeneration or risk? A narrative review of BPC-157 for musculoskeletal healing. Current Reviews in Musculoskeletal Medicine, 18(12), 611-619. PubMed
19. Lee, E., & Burgess, K. (2025). Safety of intravenous infusion of BPC157 in humans: a pilot study. Alternative Therapies in Health and Medicine, 31(5), 20-24. PubMed
20. Dalmasso, G., Charrier-Hisamuddin, L., Nguyen, H. T. T., Yan, Y., Sitaraman, S., & Merlin, D. (2008). PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology, 134(1), 166-178. PubMed
21. Pickart, L., Vasquez-Soltero, J. M., & Margolina, A. (2012). The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging. Oxidative Medicine and Cellular Longevity, 2012, 324832. PubMed
22. Chien, R. N., Liaw, Y. F., Chen, T. C., Yeh, C. T., & Sheen, I. S. (1998). Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology, 27(5), 1383-1387. PubMed
23. Zozulya, A. A., Neznamov, G. G., Siuniakov, T. S., Kost, N. V., Gabaeva, M. V., Sokolov, O. Y., et al. (2008). Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia. Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova, 108(4), 38-48. PubMed