SS-31 (Elamipretide) vs Tesamorelin

Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.

SS-31 (Elamipretide)Tesamorelin
CategoryPeptidesPeptides
Standard DoseResearch indicates 0.05-0.25 mg/kg daily via subcutaneous injection. Clinical trials used 4-40 mg/day IV or SC.Research indicates 2 mg administered once daily via subcutaneous injection (FDA-approved dose for HIV lipodystrophy).
TimingMorning dosing preferred. No food timing restrictions.Morning administration on empty stomach. Consistent daily timing recommended.
Cycle DurationClinical trials ranged from single dose to 48 weeks. Optimal cycle length not established.26+ weeks in clinical trials. Long-term use is common; effects are not sustained after discontinuation.
Evidence LevelEmerging (Phase 2/3 trials)Strong (FDA-approved indication), Moderate (longevity)

Mechanism

SS-31 (D-Arg-Dmt-Lys-Phe-NH2, also known as elamipretide/Bendavia) is a cell-permeable tetrapeptide that localizes to the inner mitochondrial membrane and binds cardiolipin via electrostatic interactions. This stabilizes cardiolipin against oxidative damage, preserving cristae integrity, reducing ROS production, and maintaining mitochondrial ATP production. SS-31 interacts with proteins in two functional groups: oxidative phosphorylation complexes and 2-oxoglutarate metabolic enzymes — all known cardiolipin binders. It restores mitochondrial function without acting as a direct antioxidant.

Standard Dosing

Research indicates 0.05-0.25 mg/kg daily via subcutaneous injection. Clinical trials used 4-40 mg/day IV or SC.

Timing

Morning dosing preferred. No food timing restrictions.

Cycle Duration

Clinical trials ranged from single dose to 48 weeks. Optimal cycle length not established.

Side Effects

  • Injection site reactions
  • Headache
  • Diarrhea (in clinical trials)
  • Nausea

Contraindications

  • Pregnancy and breastfeeding
  • Severe renal impairment (peptide clearance concern)
  • Not commercially available
  • Clinical trial participants only

Best Stacking Partners

MOTS-cHumaninEpitalon
B

Tesamorelin

Peptides

Mechanism

Tesamorelin is an FDA-approved synthetic 44-amino acid GHRH analog with a trans-3-hexenoic acid modification at the N-terminal tyrosine that confers resistance to DPP-IV degradation. It binds GHRH receptors on anterior pituitary somatotrophs, stimulating endogenous GH production and secretion while maintaining pulsatile release patterns. Tesamorelin selectively reduces visceral adipose tissue (15-20% reduction in trials) while preserving subcutaneous fat, and markedly increases plasma GH and IGF-1 levels with once-daily dosing.

Standard Dosing

Research indicates 2 mg administered once daily via subcutaneous injection (FDA-approved dose for HIV lipodystrophy).

Timing

Morning administration on empty stomach. Consistent daily timing recommended.

Cycle Duration

26+ weeks in clinical trials. Long-term use is common; effects are not sustained after discontinuation.

Side Effects

  • Injection site reactions (erythema, pruritus)
  • Arthralgia
  • Peripheral edema
  • Myalgia
  • Paresthesia
  • Elevated blood glucose

Contraindications

  • Active cancer or pituitary tumors
  • Pregnancy (Category X)
  • Hypersensitivity to GHRH analogs
  • Disruption of hypothalamic-pituitary axis from surgery/radiation
  • Active cancer
  • Pregnancy
  • Pituitary surgery or disease

Best Stacking Partners

IpamorelinAOD-9604

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