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AI comparison summary

Biggest differences across SS-31 (Elamipretide) · MOTS-c · Tesamorelin

Focused on evidence grade, pharmacokinetics, and risks/interactions — with inline citations to the primary references on each peptide page.

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SS-31 (Elamipretide)

Grade BMitochondrial

Overview

Evidence grade: Grade B
Category: Mitochondrial
Primary focus: Mitochondrial membrane stabilization
Summary: Investigated for primary mitochondrial myopathies, heart failure, and age-related muscle dysfunction. Multiple Phase 2/3 human trials completed with mixed but mechanistically promising results.

Mechanism

Mechanism of action: Cell-permeable tetrapeptide that selectively binds cardiolipin on the inner mitochondrial membrane, preserving cristae architecture, improving electron transport chain efficiency, and reducing reactive oxygen species generation.
Evidence explainer: Grade B — supported by preclinical evidence plus at least one small human trial, pharmacokinetic study, or strong translational rationale. Human long-term safety is incomplete.

Pharmacokinetics

Route: Subcutaneous injection
Half-life: ~2.5 hours
PK notes: SS-31 (Elamipretide) is administered subcutaneous injection with an approximate systemic half-life of ~2.5 hours. Steady-state and tissue-level effects can outlast plasma concentration, which is why dosing frequency (Daily) is designed to match receptor kinetics rather than plasma exposure. Cell-permeable tetrapeptide that selectively binds cardiolipin on the inner mitochondrial membrane, preserving cristae architecture, improving electron transport chain efficiency, and reducing reactive oxygen species generation.

Administration

Typical dose: 40 mg
Frequency: Daily
Cycle length: Cyclical, physician-supervised
Timing: Morning
Protocol steps: Route: Subcutaneous injection. Typical starting dose 40 mg, Daily.
Timing: Morning — keep it the same each dosing day to make effects legible.
Cycle length: Cyclical, physician-supervised. Reassess with bloods and symptom logs before repeating.
Rotate sites across the abdomen (avoiding a 2 cm radius around the navel), outer thighs and flanks. Never inject through a bruise or mole.

Benefits

Reported benefits: Restored mitochondrial ATP production in preclinical models
Improved 6-minute walk distance in mitochondrial myopathy trials
Reduced oxidative stress markers
Common stacks: CoQ10, Urolithin A, NMN

Risks

Side effects: Injection site reactions
Headache
Long-term safety still under study
Contraindications: Pregnancy
Active malignancy (theoretical)
Interactions: Antioxidant therapies — Mechanistic overlap; effect unclear.
Legal status: Investigational. Not FDA-approved; available only via clinical trials or as a research chemical.

MOTS-c

Grade BMitochondrial

Overview

Evidence grade: Grade B
Category: Mitochondrial
Primary focus: Mitochondrial signaling
Summary: Promising mitokine with metabolic and exercise-mimetic effects in rodents. Early human pharmacokinetic data is emerging.

Mechanism

Mechanism of action: Mitochondrial-derived peptide encoded within the 12S rRNA. Activates AMPK, improves insulin sensitivity, and regulates nuclear gene expression in response to metabolic stress.
Evidence explainer: Grade B — supported by preclinical evidence plus at least one small human trial, pharmacokinetic study, or strong translational rationale. Human long-term safety is incomplete.

Pharmacokinetics

Route: Subcutaneous
Half-life: ~2 hours
PK notes: MOTS-c is administered subcutaneous with an approximate systemic half-life of ~2 hours. Steady-state and tissue-level effects can outlast plasma concentration, which is why dosing frequency (2–3× weekly) is designed to match receptor kinetics rather than plasma exposure. Mitochondrial-derived peptide encoded within the 12S rRNA. Activates AMPK, improves insulin sensitivity, and regulates nuclear gene expression in response to metabolic stress.

Administration

Typical dose: 5–10 mg
Frequency: 2–3× weekly
Cycle length: 8–12 weeks
Timing: Pre-training mornings
Protocol steps: Route: Subcutaneous. Typical starting dose 5–10 mg, 2–3× weekly.
Timing: Pre-training mornings — keep it the same each dosing day to make effects legible.
Cycle length: 8–12 weeks. Reassess with bloods and symptom logs before repeating.
Rotate sites across the abdomen (avoiding a 2 cm radius around the navel), outer thighs and flanks. Never inject through a bruise or mole.

Benefits

Reported benefits: Improved glucose disposal in preclinical models
Enhanced exercise capacity
Mitochondrial biogenesis signaling
Common stacks: NMN, Urolithin A, Zone 2 training

Risks

Side effects: Mild flushing
Transient fatigue
Injection site reaction
Contraindications: Active malignancy
Pregnancy
Interactions: Metformin — Both activate AMPK — stacking effect unclear.
SGLT2 inhibitors — Potential additive glucose-lowering.
Legal status: Research chemical. Not approved for therapeutic use in humans.

Tesamorelin

Grade AGrowth Hormone

Overview

Evidence grade: Grade A
Category: Growth Hormone
Primary focus: Visceral fat, growth hormone axis
Summary: The most rigorously evidenced peptide on this site, and the only one here approved by a major regulator. FDA-approved in 2010 as Egrifta for excess abdominal fat in HIV-associated lipodystrophy, on the back of phase 3 trials showing a 15-18% reduction in visceral adipose tissue against placebo. Everything outside that indication — the anti-ageing and body-composition uses it is sold for — is extrapolation from a population that is not you.

Mechanism

Mechanism of action: A synthetic analogue of the full 44-amino-acid human growth hormone releasing factor, with a hexenoyl group on the N-terminus that slows enzymatic degradation. It binds pituitary GHRH receptors to restore pulsatile growth hormone secretion, raising IGF-1 and shifting adipose metabolism preferentially against visceral rather than subcutaneous fat.
Evidence explainer: Grade A — supported by multiple randomised human trials or an approved regulatory indication. Mechanism, dosing and safety are well characterised in humans.

Pharmacokinetics

Route: Subcutaneous injection
Half-life: ~26 minutes in plasma; the growth hormone rise it triggers persists 4-6 hours
PK notes: Tesamorelin is administered subcutaneous injection with an approximate systemic half-life of ~26 minutes in plasma; the growth hormone rise it triggers persists 4-6 hours. Steady-state and tissue-level effects can outlast plasma concentration, which is why dosing frequency (Once daily) is designed to match receptor kinetics rather than plasma exposure. A synthetic analogue of the full 44-amino-acid human growth hormone releasing factor, with a hexenoyl group on the N-terminus that slows enzymatic degradation. It binds pituitary GHRH receptors to restore pulsatile growth hormone secretion, raising IGF-1 and shifting adipose metabolism preferentially against visceral rather than subcutaneous fat.

Administration

Typical dose: 2 mg (1.28 mg for the newer F8/WR formulation)
Frequency: Once daily
Cycle length: 26 weeks in the pivotal trials; benefit reverses on stopping
Timing: Bedtime, to sit with the natural overnight GH pulse
Protocol steps: Route: Subcutaneous injection. Typical starting dose 2 mg (1.28 mg for the newer F8/WR formulation), Once daily.
Timing: Bedtime, to sit with the natural overnight GH pulse — keep it the same each dosing day to make effects legible.
Cycle length: 26 weeks in the pivotal trials; benefit reverses on stopping. Reassess with bloods and symptom logs before repeating.
Rotate sites across the abdomen (avoiding a 2 cm radius around the navel), outer thighs and flanks. Never inject through a bruise or mole.

Benefits

Reported benefits: 15-18% reduction in visceral adipose tissue versus placebo in phase 3 trials
Improved triglycerides and cholesterol alongside the fat loss
Raises IGF-1 without the supraphysiological spikes of exogenous growth hormone
Does not reduce subcutaneous fat, which is metabolically less harmful
Common stacks: Zone 2 cardio, Resistance training, Regular HbA1c and IGF-1 monitoring

Risks

Side effects: Injection site reactions, the commonest complaint in trials
Joint pain and peripheral oedema, both dose-related and GH-mediated
Raised blood glucose and reduced insulin sensitivity — monitor if prediabetic
Carpal tunnel symptoms at higher exposures
Contraindications: Active malignancy — growth hormone is mitogenic and IGF-1 is a growth signal
Pituitary disease, pituitary surgery or head irradiation
Pregnancy and lactation
Diabetic retinopathy
Interactions: Insulin and sulfonylureas — Tesamorelin worsens insulin sensitivity; glycaemic control may need adjusting.
Corticosteroids — Blunt the GH response and add their own metabolic burden.
GHRH analogues (CJC-1295) — Same receptor. Stacking adds risk, not effect.
Legal status: FDA-approved as Egrifta and Egrifta SV/WR for HIV-associated lipodystrophy only, and prescription-only. Use for body composition or anti-ageing is off-label. Material sold online as research-grade tesamorelin is not the approved product and carries no purity guarantee.

Attribute	SS-31 (Elamipretide) Grade BMitochondrial	MOTS-c Grade BMitochondrial	Tesamorelin Grade AGrowth Hormone
Overview
Evidence grade	Grade B	Grade B	Grade A
Category	Mitochondrial	Mitochondrial	Growth Hormone
Primary focus	Mitochondrial membrane stabilization	Mitochondrial signaling	Visceral fat, growth hormone axis
Summary	Investigated for primary mitochondrial myopathies, heart failure, and age-related muscle dysfunction. Multiple Phase 2/3 human trials completed with mixed but mechanistically promising results.	Promising mitokine with metabolic and exercise-mimetic effects in rodents. Early human pharmacokinetic data is emerging.	The most rigorously evidenced peptide on this site, and the only one here approved by a major regulator. FDA-approved in 2010 as Egrifta for excess abdominal fat in HIV-associated lipodystrophy, on the back of phase 3 trials showing a 15-18% reduction in visceral adipose tissue against placebo. Everything outside that indication — the anti-ageing and body-composition uses it is sold for — is extrapolation from a population that is not you.
Mechanism
Mechanism of action	Cell-permeable tetrapeptide that selectively binds cardiolipin on the inner mitochondrial membrane, preserving cristae architecture, improving electron transport chain efficiency, and reducing reactive oxygen species generation.	Mitochondrial-derived peptide encoded within the 12S rRNA. Activates AMPK, improves insulin sensitivity, and regulates nuclear gene expression in response to metabolic stress.	A synthetic analogue of the full 44-amino-acid human growth hormone releasing factor, with a hexenoyl group on the N-terminus that slows enzymatic degradation. It binds pituitary GHRH receptors to restore pulsatile growth hormone secretion, raising IGF-1 and shifting adipose metabolism preferentially against visceral rather than subcutaneous fat.
Evidence explainer	Grade B — supported by preclinical evidence plus at least one small human trial, pharmacokinetic study, or strong translational rationale. Human long-term safety is incomplete.	Grade B — supported by preclinical evidence plus at least one small human trial, pharmacokinetic study, or strong translational rationale. Human long-term safety is incomplete.	Grade A — supported by multiple randomised human trials or an approved regulatory indication. Mechanism, dosing and safety are well characterised in humans.
Pharmacokinetics
Route	Subcutaneous injection	Subcutaneous	Subcutaneous injection
Half-life	~2.5 hours	~2 hours	~26 minutes in plasma; the growth hormone rise it triggers persists 4-6 hours
PK notes	SS-31 (Elamipretide) is administered subcutaneous injection with an approximate systemic half-life of ~2.5 hours. Steady-state and tissue-level effects can outlast plasma concentration, which is why dosing frequency (Daily) is designed to match receptor kinetics rather than plasma exposure. Cell-permeable tetrapeptide that selectively binds cardiolipin on the inner mitochondrial membrane, preserving cristae architecture, improving electron transport chain efficiency, and reducing reactive oxygen species generation.	MOTS-c is administered subcutaneous with an approximate systemic half-life of ~2 hours. Steady-state and tissue-level effects can outlast plasma concentration, which is why dosing frequency (2–3× weekly) is designed to match receptor kinetics rather than plasma exposure. Mitochondrial-derived peptide encoded within the 12S rRNA. Activates AMPK, improves insulin sensitivity, and regulates nuclear gene expression in response to metabolic stress.	Tesamorelin is administered subcutaneous injection with an approximate systemic half-life of ~26 minutes in plasma; the growth hormone rise it triggers persists 4-6 hours. Steady-state and tissue-level effects can outlast plasma concentration, which is why dosing frequency (Once daily) is designed to match receptor kinetics rather than plasma exposure. A synthetic analogue of the full 44-amino-acid human growth hormone releasing factor, with a hexenoyl group on the N-terminus that slows enzymatic degradation. It binds pituitary GHRH receptors to restore pulsatile growth hormone secretion, raising IGF-1 and shifting adipose metabolism preferentially against visceral rather than subcutaneous fat.
Administration
Typical dose	40 mg	5–10 mg	2 mg (1.28 mg for the newer F8/WR formulation)
Frequency	Daily	2–3× weekly	Once daily
Cycle length	Cyclical, physician-supervised	8–12 weeks	26 weeks in the pivotal trials; benefit reverses on stopping
Timing	Morning	Pre-training mornings	Bedtime, to sit with the natural overnight GH pulse
Protocol steps	Route: Subcutaneous injection. Typical starting dose 40 mg, Daily. Timing: Morning — keep it the same each dosing day to make effects legible. Cycle length: Cyclical, physician-supervised. Reassess with bloods and symptom logs before repeating. Rotate sites across the abdomen (avoiding a 2 cm radius around the navel), outer thighs and flanks. Never inject through a bruise or mole.	Route: Subcutaneous. Typical starting dose 5–10 mg, 2–3× weekly. Timing: Pre-training mornings — keep it the same each dosing day to make effects legible. Cycle length: 8–12 weeks. Reassess with bloods and symptom logs before repeating. Rotate sites across the abdomen (avoiding a 2 cm radius around the navel), outer thighs and flanks. Never inject through a bruise or mole.	Route: Subcutaneous injection. Typical starting dose 2 mg (1.28 mg for the newer F8/WR formulation), Once daily. Timing: Bedtime, to sit with the natural overnight GH pulse — keep it the same each dosing day to make effects legible. Cycle length: 26 weeks in the pivotal trials; benefit reverses on stopping. Reassess with bloods and symptom logs before repeating. Rotate sites across the abdomen (avoiding a 2 cm radius around the navel), outer thighs and flanks. Never inject through a bruise or mole.
Benefits
Reported benefits	Restored mitochondrial ATP production in preclinical models Improved 6-minute walk distance in mitochondrial myopathy trials Reduced oxidative stress markers	Improved glucose disposal in preclinical models Enhanced exercise capacity Mitochondrial biogenesis signaling	15-18% reduction in visceral adipose tissue versus placebo in phase 3 trials Improved triglycerides and cholesterol alongside the fat loss Raises IGF-1 without the supraphysiological spikes of exogenous growth hormone Does not reduce subcutaneous fat, which is metabolically less harmful
Common stacks	CoQ10, Urolithin A, NMN	NMN, Urolithin A, Zone 2 training	Zone 2 cardio, Resistance training, Regular HbA1c and IGF-1 monitoring
Risks
Side effects	Injection site reactions Headache Long-term safety still under study	Mild flushing Transient fatigue Injection site reaction	Injection site reactions, the commonest complaint in trials Joint pain and peripheral oedema, both dose-related and GH-mediated Raised blood glucose and reduced insulin sensitivity — monitor if prediabetic Carpal tunnel symptoms at higher exposures
Contraindications	Pregnancy Active malignancy (theoretical)	Active malignancy Pregnancy	Active malignancy — growth hormone is mitogenic and IGF-1 is a growth signal Pituitary disease, pituitary surgery or head irradiation Pregnancy and lactation Diabetic retinopathy
Interactions	Antioxidant therapies — Mechanistic overlap; effect unclear.	Metformin — Both activate AMPK — stacking effect unclear. SGLT2 inhibitors — Potential additive glucose-lowering.	Insulin and sulfonylureas — Tesamorelin worsens insulin sensitivity; glycaemic control may need adjusting. Corticosteroids — Blunt the GH response and add their own metabolic burden. GHRH analogues (CJC-1295) — Same receptor. Stacking adds risk, not effect.
Legal status	Investigational. Not FDA-approved; available only via clinical trials or as a research chemical.	Research chemical. Not approved for therapeutic use in humans.	FDA-approved as Egrifta and Egrifta SV/WR for HIV-associated lipodystrophy only, and prescription-only. Use for body composition or anti-ageing is off-label. Material sold online as research-grade tesamorelin is not the approved product and carries no purity guarantee.

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