Ipamorelin vs Sermorelin

Molecular formula

C₃₈H₄₉N₉O₅

Molecular weight

711.85 g/mol

Half-life

2 hours

Bioavailability

High when injected subcutaneously

CAS number

170851-70-4

Molecular formula

C₁₄₉H₂₄₆N₄₄O₄₂S

Molecular weight

3357.9 g/mol

Half-life

10-20 minutes

Bioavailability

High when injected subcutaneously; degraded orally

CAS number

86168-78-7

Common

• Mild headache
• Injection site reactions
• Water retention
• Increased appetite

Uncommon

• Tingling in hands or feet
• Joint stiffness

Serious

• Allergic reaction

Common

• Injection site reactions
• Facial flushing

Uncommon

• Headache
• Sleepiness or drowsiness
• Nausea
• Hyperactivity or difficulty sleeping

Serious

• Severe allergic reaction

Evidence level

Moderate human trials (Phase 1-2)

FDA status

Research compound

Safety overview

Ipamorelin's main selling point is that it raises growth hormone without raising cortisol or ACTH — two stress hormones that similar peptides do raise. That was shown in pigs, and it held even at doses more than 200 times higher than the amount needed to raise growth hormone [1]. It has not been checked in people. The two published human studies measured ipamorelin and growth hormone only; neither one assayed cortisol, ACTH or prolactin [2][3]. Most of what we know about safety in people comes from a single trial in patients recovering from bowel surgery. 114 people took part: 56 got ipamorelin through an IV for up to seven days, and 58 got a placebo. Most side effects were mild to moderate, and were the kind you would expect after surgery [3]. Serious problems happened at about the same rate in both groups — roughly 1 in 6 either way (17.9% on ipamorelin, 15.5% on placebo). But three things were more common on ipamorelin: low potassium in about 1 in 8 people versus about 1 in 30 on placebo (12.5% vs 3.4%), trouble sleeping in about 1 in 9 versus about 1 in 19 (10.7% vs 5.2%), and high blood sugar at discharge in about 1 in 7 versus about 1 in 12 (14.3% vs 8.6%) [6]. Two people taking ipamorelin died. Both had colon cancer surgery, and in both cases the surgical join in the bowel leaked afterward. Nobody on the placebo died. The FDA says it is unclear whether those deaths had anything to do with ipamorelin — but it pointed to them, along with the potassium and blood sugar differences, when it recommended in October 2024 against letting pharmacies compound ipamorelin [6].

Contraindications

• Active cancer or history of cancer
• Pregnancy or breastfeeding
• Pituitary disorders or tumors
• Known allergy to peptide components
• Children and adolescents (growth plates still open)

Evidence level

Moderate human trials (Phase 1-2)

FDA status

Not currently FDA approved. GEREF (sermorelin) was approved in 1997 for growth failure in children with GH deficiency; EMD Serono discontinued it in 2008 and FDA withdrew the approvals at its request in 2009, not for safety or effectiveness reasons. Sermorelin sold today is compounded, not an FDA-approved product.

Safety overview

Sermorelin works through the body's own GH feedback, which limits excessive hormone levels. [8][13] On the GEREF label, the most common reaction to repeated injections was a local reaction (about 1 in 6 patients); headache, flushing, dizziness, hyperactivity and somnolence each occurred in under 1%, and many patients developed anti-GRF antibodies. [16] Facial flushing and injection-site pain were the most commonly reported events in the pediatric studies. [6] GEREF was FDA-approved in 1997 for children with GH deficiency. [7]

Contraindications

• Active cancer or history of cancer
• Pregnancy or breastfeeding
• Known allergy to sermorelin or any peptide components
• Pituitary tumors or other pituitary disorders
• Diabetic retinopathy