Peptide Side Effects: What the Labels and Trials Actually Report

Three kinds of evidence, and why they are not equal

A side-effect figure means something only if you know where it came from. The strongest is a drug label: a regulator has reviewed controlled trials and the label reports how often each effect occurred on the drug and on placebo. Next come published trials, often small and short, that report what they happened to see. Last come case reports and user accounts, which show that something can happen but not how often, because nobody counted the people it did not happen to.

That is why no single rate applies to "peptides". Injection-site reactions are a good example: on the tesamorelin label they occurred in 25% of people on the drug and 14% on placebo in the first 26 weeks,¹ a figure that belongs to that drug and those trials, not to injections in general.

GLP-1 medicines: the best-measured side effects

Semaglutide and tirzepatide have side-effect data from trials involving tens of thousands of people. The most common effects are gastrointestinal. Nausea affected 44% of people on Wegovy against 16% on placebo, and 25 to 29% on Zepbound against 8%; the labels' lists of the most common reactions also include diarrhoea, vomiting, constipation, abdominal pain, fatigue and hair loss.^2,3 In the trial that compared tirzepatide and semaglutide directly in type 2 diabetes, nausea rates were close (17 to 22% against 18%) and most events were mild to moderate.⁴ They drive people off treatment too: in STEP 1, 4.5% stopped semaglutide because of gastrointestinal events against 0.8% on placebo,⁵ and in the large SELECT trial 16.6% stopped because of an adverse event against 8.2%.⁶

The labels' warnings cover less common but serious problems: pancreatitis, gallbladder disease, kidney injury from dehydration, severe gastrointestinal reactions, low blood sugar with insulin or sulfonylureas, aspiration during anaesthesia, and a boxed warning about thyroid C-cell tumours seen in rodents.^2,3 Interactions with other medicines are covered in our GLP-1 drug interactions guide.

Drugs that raise growth hormone

Tesamorelin (EGRIFTA SV), the one approved drug in this group, shows the pattern. Its label warns that raising growth hormone can cause fluid retention, including oedema, joint pain and carpal tunnel syndrome, usually transient or resolving on stopping; that it can cause glucose intolerance, with HbA_1c reaching 6.5% or more in 5% of treated patients against 1% on placebo by week 26; and that hypersensitivity reactions occurred in trials.¹

MK-677, an oral ghrelin mimetic that is not a peptide, raised fasting glucose in its first trial in older adults.⁷ In a two-year trial in 65 healthy adults aged 60 to 81, it added 2.7 kg of body weight against 0.8 kg on placebo, increased limb fat, raised fasting glucose by about 5 mg/dL, reduced insulin sensitivity and raised cortisol; the most frequent side effects were increased appetite, which subsided within a few months, and transient mild leg swelling and muscle pain.⁸ Its trial in older adults recovering from hip fracture was terminated early because of a signal of congestive heart failure.⁹ For CJC-1295, the two published trials in healthy adults raised growth hormone and IGF-1 for days after one injection,¹⁰ and FDA reports having identified serious adverse events associated with it, including increased heart rate and a systemic vasodilatory reaction, while noting that clinical data are limited.¹¹ For ipamorelin, sermorelin and the GHRPs, there are too few human safety studies to give rates.

Melanocortin drugs: PT-141 and melanotan II

Bremelanotide (PT-141), approved as Vyleesi, has measured rates: nausea in 40% of patients against 1.3% on placebo, and flushing, injection-site reactions, headache and vomiting among the most common reactions. Its label also warns of a transient rise in blood pressure after each dose and of darkening patches of skin with repeated use.¹²

Melanotan II, its unapproved relative, was tested in only a handful of people. In its first study, two of three men developed darker skin on the face, upper body and buttocks, and spontaneous erections occurred;¹³ in trials in men with erectile dysfunction, 17 of 20 had erections without sexual stimulation.¹⁴ Its use outside trials has produced case reports of melanoma¹⁵ and of priapism after an overdose,¹⁶ and a review of unregulated use gathers these and other harms.¹⁷ Case reports cannot say how common these events are; they show only that they happen.

BPC-157, TB-500 and the absence of data

For the repair peptides the honest answer is that almost nothing has been measured in people. The entire published human safety record for BPC-157 is a 2025 pilot in which two adults at a private clinic received 10 mg and then 20 mg infusions into a vein; the authors reported no changes in heart, liver, kidney, thyroid or glucose markers and no side effects, but both had used the compound before, there was no control group, and two people cannot reveal anything uncommon.¹⁸ TB-500 has no published human safety study at all. The absence of reported side effects here is an absence of data, not evidence of safety.

Semax and selank

Semax and selank are registered in Russia, and nearly all their human studies come from Russian groups, few of them placebo-controlled and few reporting adverse effects in detail. In one trial in 70 patients with anxiety disorders, adding selank to phenazepam reduced phenazepam's side effects, which says more about phenazepam than about selank's own safety.¹⁹ Neither has safety data of the kind a label reports. One animal finding is worth knowing: in rats, semax on its own did not change dopamine, but given before d-amphetamine it sharply increased amphetamine's effects, a reason for caution about combining it with stimulants, about which there are no human data.²⁰ Our semax and selank article covers the rest of their evidence.

Other approved peptide drugs: side effects by the numbers

Approved peptide drugs outside the GLP-1 class show the same pattern: the side effects follow the mechanism, and the label measures them. Tesamorelin, which raises growth hormone, raises IGF-1 too; in its trials 47% of patients had IGF-1 above 2 standard deviation scores and 36% above 3 at 26 weeks, and its label tells prescribers to monitor IGF-1 and consider stopping if it stays high.²¹ Trofinetide, the Rett syndrome drug, caused diarrhoea in 80.6% of patients against 19.1% on placebo in its phase 3 trial.²² Etelcalcetide, which lowers parathyroid hormone, lowered blood calcium in 68.9% of patients in its head-to-head trial against cinacalcet, where 59.8% had the same effect.²³ And difelikefalin, a kappa opioid agonist for itch in dialysis, carries label warnings for dizziness, sleepiness and changes in mental status.²⁴ These numbers exist because the drugs went through trials designed to find them; that is exactly what the research peptides lack.

One more case shows what happens when a cosmetic ingredient is used like a drug. Argireline, a topical anti-wrinkle peptide, is considered safe in cosmetics only up to low concentrations; a woman who had it injected into her forehead and temples developed mycobacterial abscesses that took five months of antibiotics to clear.²⁵ Our argireline article explains why the cream and the injection are not comparable.

The cancer question

The concern is biological: several of these compounds raise growth factors or encourage blood-vessel growth, which tumours also use. For GLP-1 medicines the concern came from rodent thyroid tumours, and a Scandinavian cohort study of GLP-1 users found no substantially increased risk of thyroid cancer over a mean of about four years.²⁶ For the research peptides there are no human cancer data in either direction. Our peptides and cancer article goes through the evidence compound by compound.

What monitoring can and cannot do

For approved drugs, follow the label's monitoring: tesamorelin's advises evaluating glucose before and during treatment,¹ and the GLP-1 labels advise monitoring kidney function in people with vomiting or diarrhoea and investigating suspected gallbladder disease.^2,3 For research peptides no validated monitoring plan exists. A blood test for IGF-1 or glucose measures a marker; it does not show that a compound with no safety studies is safe.

If you have a side effect from any medicine or product, FDA's MedWatch programme takes reports from patients and consumers as well as professionals.²⁷

Frequently asked questions

Are peptides safe?

It depends on the peptide. Approved ones such as semaglutide or tesamorelin have labels listing their side effects and how often they occur. Most research peptides, including BPC-157 and TB-500, have almost no human safety data, so nobody can say how safe they are.

What are the most common peptide side effects?

For GLP-1 medicines, gastrointestinal effects: nausea in 25 to 44% on the weight-management doses, depending on the drug. For drugs that raise growth hormone, fluid retention, joint pain and higher blood sugar. For bremelanotide, nausea in 40%.

Do peptides affect hormones?

Some are designed to. Growth hormone secretagogues raise growth hormone and IGF-1, which can reduce insulin sensitivity; tesamorelin's label reports HbA1c reaching 6.5% or more in 5% of treated patients against 1% on placebo.

Can peptides cause cancer?

There are no human data showing that research peptides cause cancer, and none showing that they do not. GLP-1 labels carry a boxed warning based on rodent thyroid tumours; a large Scandinavian cohort study found no substantially increased thyroid cancer risk in people.

Where do I report a side effect?

In the US, FDA's MedWatch programme accepts reports from patients and consumers as well as healthcare professionals.

Related on Grey Peptides

• GLP-1 drug interactions
• Peptides and cancer
• MK-677 complete guide
• Melanotan II encyclopedia entry
• BPC-157 encyclopedia entry
• Interaction checker

Sources

1. Theratechnologies Inc. EGRIFTA SV (tesamorelin) for injection, US prescribing information: section 5 (fluid retention with edema, arthralgia and carpal tunnel syndrome; glucose intolerance, HbA1c 6.5% or higher in 5% vs 1%; hypersensitivity; injection site reactions 25% vs 14% over 26 weeks; evaluate glucose before and during therapy). DailyMed version of July 31, 2026, read September 30, 2026.
2. Novo Nordisk. WEGOVY (semaglutide) injection and tablets, US prescribing information: section 6 (nausea 44% vs 16% placebo; most common adverse reactions) and section 5 (warnings; renal and gallbladder monitoring). DailyMed version of June 30, 2026, read September 30, 2026.
3. Eli Lilly and Company. ZEPBOUND (tirzepatide) injection, US prescribing information: section 6 (nausea 25-29% vs 8% placebo; most common adverse reactions) and section 5 (warnings). DailyMed version of September 2, 2026, read September 30, 2026.
4. Frías, J. P. et al. (2021). Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine, 385(6), 503-515. PMID: 34170647 · doi:10.1056/NEJMoa2107519
5. Wilding, J. P. H. et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 384(11), 989-1002. PMID: 33567185 · doi:10.1056/NEJMoa2032183
6. Lincoff, A. M. et al. (2023). Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine, 389(24), 2221-2232. PMID: 37952131 · doi:10.1056/NEJMoa2307563
7. Chapman, I. M. et al. (1996). Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects. Journal of Clinical Endocrinology and Metabolism, 81(12), 4249-4257. PMID: 8954023 · doi:10.1210/jcem.81.12.8954023
8. Nass, R. et al. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Annals of Internal Medicine, 149(9), 601-611. PMID: 18981485 · doi:10.7326/0003-4819-149-9-200811040-00003
9. Adunsky, A. et al. (2011). MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Archives of Gerontology and Geriatrics, 53(2), 183-189. PMID: 21067829 · doi:10.1016/j.archger.2010.10.004
10. Teichman, S. L. et al. (2006). Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. Journal of Clinical Endocrinology and Metabolism, 91(3), 799-805. PMID: 16352683 · doi:10.1210/jc.2005-1536
11. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks: CJC-1295 (serious adverse events including increased heart rate and systemic vasodilatory reaction; clinical data limited). Content current as of April 22, 2026; read September 30, 2026. FDA
12. Cosette Pharmaceuticals. VYLEESI (bremelanotide) injection, US prescribing information: nausea 40.0% vs 1.3% placebo; most common adverse reactions nausea, flushing, injection site reactions, headache and vomiting; transient increase in blood pressure; focal hyperpigmentation. DailyMed version of November 18, 2025, read September 30, 2026.
13. Dorr, R. T. et al. (1996). Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sciences, 58(20), 1777-1784. PMID: 8637402 · doi:10.1016/0024-3205(96)00160-9
14. Wessells, H. et al. (2000). Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. International Journal of Impotence Research, 12 Suppl 4, S74-S79. PMID: 11035391 · doi:10.1038/sj.ijir.3900582
15. Paurobally, D. et al. (2011). Melanotan-associated melanoma. British Journal of Dermatology, 164(6), 1403-1405. PMID: 21564053 · doi:10.1111/j.1365-2133.2011.10273.x
16. Devlin, J. et al. (2013). Melanotan II overdose associated with priapism. Clinical Toxicology, 51(4), 383. PMID: 23537392 · doi:10.3109/15563650.2013.784775
17. Habbema, L. et al. (2017). Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. International Journal of Dermatology, 56(10), 975-980. PMID: 28266027 · doi:10.1111/ijd.13585
18. Lee, E. et al. (2025). Safety of Intravenous Infusion of BPC157 in Humans: A Pilot Study. Alternative Therapies in Health and Medicine, 31(5), 20-24. PMID: 40131143
19. Medvedev, V. E. et al. (2015). [Optimization of the treatment of anxiety disorders with selank]. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 115(6), 33-40. PMID: 26356395 · doi:10.17116/jnevro20151156133-40
20. Eremin, K. O., et al. (2005). Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res, 30(12), 1493-500. PMID: 16362768
21. Theratechnologies. EGRIFTA WR (tesamorelin) for injection US prescribing information, section 5.2 (DailyMed set 839334d3-8c1d-4c26-9036-2ab524a6ea75, effective July 29, 2026); read October 2, 2026.
22. Neul, J. L., et al. (2023). Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. Nat Med, 29(6), 1468-1475. PMID: 37291210
23. Block, G. A., et al. (2017). Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA, 317(2), 156-164. PMID: 28097356
24. Vifor (International). KORSUVA (difelikefalin) injection US prescribing information, section 5 (DailyMed set 0c7b81f2-0fd3-47cb-8b0f-185e07f19c87, effective August 26, 2025); read October 2, 2026.
25. Chen, C. F., et al. (2021). Mycobacterium abscessus infection after facial injection of argireline: A case report. World J Clin Cases, 9(8), 1996-2000. PMID: 33748252
26. Pasternak, B. et al. (2024). Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study. BMJ, 385, e078225. PMID: 38683947 · doi:10.1136/bmj-2023-078225
27. U.S. Food and Drug Administration. MedWatch: The FDA Safety Information and Adverse Event Reporting Program. Content current as of September 25, 2026; read September 30, 2026. FDA

This article summarises labels, trials and case reports. It is not medical advice, and the absence of a side effect from this page does not mean a compound is safe. Report side effects to your doctor and to MedWatch.