Peptide Side Effects: What to Expect by Compound

GLP-1 receptor agonists (tirzepatide, semaglutide, retatrutide) have the most well-documented side effect profile from large clinical trials.

Common Side Effects (affecting 10-30% of users)

• Nausea: The most common side effect, occurring in 20-30% of users. Typically worst during dose escalation and improving significantly over 4-8 weeks
• Diarrhea: Affects 15-20% of users. Usually transient
• Constipation: Occurs in 10-15% of users due to slowed gastric emptying
• Decreased appetite: Intentional effect but can become excessive in some individuals
• Injection site reactions: Mild redness, swelling, or itching at the injection site

Less Common Side Effects (1-10%)

• Headache and fatigue
• Abdominal pain
• Gastroesophageal reflux (GERD)
• Hair thinning (likely related to rapid weight loss rather than the peptide directly)

Serious Side Effects (rare but documented)

• Pancreatitis: Rare (<0.5%) but requires immediate medical attention. Symptoms include severe abdominal pain radiating to the back
• Gallbladder problems: Gallstones and cholecystitis occur at higher rates during rapid weight loss
• Thyroid C-cell tumors: Observed in rodents; relevance to humans uncertain but GLP-1 agonists carry a boxed warning. Contraindicated with personal/family history of medullary thyroid carcinoma

Side effect profiles vary between specific GLP-1 compounds. For detailed comparisons, see Tirzepatide vs Semaglutide and Semaglutide vs Liraglutide.

GH secretagogues and GHRH analogs (sermorelin, tesamorelin, ipamorelin, CJC-1295, MK-677) share a common side effect profile related to elevated growth hormone and IGF-1 levels.

Common Side Effects

• Water retention/edema: The most common effect. Noticeable as puffiness in the face, hands, or ankles. Usually dose-dependent and reversible
• Joint stiffness: Related to fluid retention in joint spaces. Typically mild
• Numbness/tingling: Carpal tunnel-like symptoms from fluid retention pressing on nerves
• Increased hunger: Particularly with GHRP-6 and MK-677, which stimulate ghrelin pathways
• Injection site reactions: Mild, transient reactions common with subcutaneous administration

Less Common Side Effects

• Elevated blood sugar: GH can reduce insulin sensitivity. Monitor blood glucose, especially with pre-existing insulin resistance
• Headache: Usually mild and transient
• Facial flushing: Particularly with sermorelin
• Lightheadedness: Occasional, usually related to timing of administration

Long-Term Considerations

Sustained elevation of GH and IGF-1 carries theoretical concerns related to cell proliferation. While stimulating natural GH production maintains physiological feedback loops (unlike exogenous GH injection), prolonged use should involve periodic blood work monitoring IGF-1 levels. Side effect profiles differ significantly between GH secretagogues — see Ipamorelin vs GHRP-6 and GHRP-2 vs GHRP-6 for detailed comparisons.

BPC-157, TB-500, and GHK-Cu generally have the most favorable side effect profiles in published research, though human data is limited.

BPC-157

• No reported toxicity across 100+ animal studies at standard research doses
• Anecdotal reports occasionally mention temporary nausea, headache, or dizziness
• Injection site reactions possible with subcutaneous administration
• No known drug interactions documented, though data is limited

TB-500 (Thymosin Beta-4)

• Headache is the most commonly reported side effect
• Temporary nausea possible
• Clinical trials for cardiac and wound healing applications showed acceptable tolerability

GHK-Cu

• Topical: mild irritation, redness, or itching possible. "Copper uglies" phenomenon (temporary skin purging) reported anecdotally
• Injectable: limited data on side effects. Theoretical concern about promoting angiogenesis in cancer patients
• Contraindicated for individuals with Wilson's disease (copper accumulation disorder)

Semax and Selank are administered intranasally and have been studied in clinical settings in Russia, where they are approved medications.

Semax

• Generally well-tolerated in clinical use
• Nasal irritation or dryness (most common)
• Mild headache occasionally reported
• May increase anxiety in some individuals (stimulatory mechanism)

Selank

• Designed as an anxiolytic — side effects are minimal in published studies
• Mild nasal irritation possible
• Fatigue reported occasionally
• May interact with GABAergic or serotonergic medications

Discontinue any peptide and consult a healthcare provider immediately if you experience:

• Severe abdominal pain (possible pancreatitis)
• Difficulty breathing or swallowing (allergic reaction)
• Persistent nausea/vomiting preventing adequate hydration
• Signs of infection at injection sites (increasing redness, warmth, pus, fever)
• Unusual swelling or rapid weight gain (fluid retention)
• Chest pain or irregular heartbeat
• Vision changes
• Any symptom that feels severe or unusual

Regular monitoring through a healthcare provider — including blood work for IGF-1, fasting glucose, liver enzymes, and kidney function — is recommended for anyone using GH secretagogues or GLP-1 agonists beyond short-term protocols.