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AI comparison summary

Biggest differences across ARA-290 (Cibinetide) · Tesamorelin · Retatrutide

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

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ARA-290 (Cibinetide)

Grade BNeuroprotective

Overview

Evidence grade: Grade B
Category: Neuroprotective
Primary focus: Neuropathy, inflammation
Summary: Promising small-molecule peptide for diabetic neuropathy and sarcoidosis-related small fiber neuropathy. Phase II trials show improved nerve fiber density and reduced neuropathic pain without raising hematocrit.

Mechanism

Mechanism of action: 11-amino-acid peptide derived from erythropoietin's helix B. Binds the innate-repair receptor (a heterodimer of EPOR + βcR) to trigger tissue-protective and anti-inflammatory cascades without activating the hematopoietic EPO receptor.
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 minutes systemic (sustained tissue receptor occupancy)
PK notes: ARA-290 (Cibinetide) is administered subcutaneous injection with an approximate systemic half-life of ~2 minutes systemic (sustained tissue receptor occupancy). 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. 11-amino-acid peptide derived from erythropoietin's helix B. Binds the innate-repair receptor (a heterodimer of EPOR + βcR) to trigger tissue-protective and anti-inflammatory cascades without activating the hematopoietic EPO receptor.

Administration

Typical dose: 4 mg
Frequency: Once daily
Cycle length: 28 days (typical trial protocol)
Timing: Morning, subcutaneous (abdominal site)
Protocol steps: Route: Subcutaneous injection. Typical starting dose 4 mg, Once daily.
Timing: Morning, subcutaneous (abdominal site) — keep it the same each dosing day to make effects legible.
Cycle length: 28 days (typical trial protocol). 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 corneal nerve fiber density in sarcoid neuropathy
Reduction in neuropathic pain scores (Phase II)
Anti-inflammatory effect without immunosuppression
No hematopoietic stimulation (unlike EPO)
Common stacks: Alpha-lipoic acid, B-complex with methylated B12, Omega-3

Risks

Side effects: Injection site irritation
Mild headache
Short-term safety profile favorable in completed trials
Contraindications: Active malignancy (limited data)
Pregnancy and lactation
Interactions: EPO / ESAs — Mechanistically distinct but caution if combined.
Legal status: Investigational drug; not approved for general human therapeutic use.

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.

Retatrutide

Grade AMetabolic

Overview

Evidence grade: Grade A
Category: Metabolic
Primary focus: Triple GIP/GLP-1/glucagon agonist
Summary: Phase II trial results showed ~24% mean weight loss at 48 weeks at the 12 mg dose — markedly exceeding tirzepatide and prior GLP-1 monotherapies. Currently in Phase III; not yet FDA-approved but expected to be a landmark obesity and metabolic therapy.

Mechanism

Mechanism of action: First-in-class triple agonist of GIP, GLP-1, and glucagon receptors. The GLP-1 and GIP arms drive glucose-dependent insulin secretion and satiety; the glucagon arm increases energy expenditure — producing the largest weight-loss effect of any incretin to date.
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: ~6 days (supports once-weekly dosing)
PK notes: Retatrutide is administered subcutaneous injection with an approximate systemic half-life of ~6 days (supports once-weekly dosing). Steady-state and tissue-level effects can outlast plasma concentration, which is why dosing frequency (Once weekly) is designed to match receptor kinetics rather than plasma exposure. First-in-class triple agonist of GIP, GLP-1, and glucagon receptors. The GLP-1 and GIP arms drive glucose-dependent insulin secretion and satiety; the glucagon arm increases energy expenditure — producing the largest weight-loss effect of any incretin to date.

Administration

Typical dose: Titrated 2 mg → 4 mg → 8 mg → 12 mg
Frequency: Once weekly
Cycle length: Ongoing; weight regain occurs on cessation
Timing: Same day each week; any time of day
Protocol steps: Route: Subcutaneous injection. Typical starting dose Titrated 2 mg → 4 mg → 8 mg → 12 mg, Once weekly.
Timing: Same day each week; any time of day — keep it the same each dosing day to make effects legible.
Cycle length: Ongoing; weight regain occurs on cessation. 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: ~24% mean weight loss at 48 weeks (Phase II)
Marked improvements in HbA1c, blood pressure, ApoB and liver fat
Convenient once-weekly dosing
Likely best-in-class cardiometabolic profile
Common stacks: Creatine monohydrate, Whey protein, Vitamin D3 + K2

Risks

Side effects: Nausea, vomiting, diarrhea (especially during titration)
Injection site reactions
Reduced appetite to the point of inadequate protein intake — pair with resistance training and protein targeting
Theoretical pancreatitis and gallbladder risk (class effect)
Contraindications: Personal or family history of medullary thyroid carcinoma
Multiple Endocrine Neoplasia type 2
Pregnancy and lactation
Prior severe reaction to GLP-1 agonists
Interactions: Insulin and sulfonylureas — Risk of hypoglycemia — dose reduction usually required.
Oral medications — Delayed gastric emptying may alter absorption; separate timing for narrow-therapeutic-index drugs.
Legal status: Investigational; not yet FDA-approved. Currently available only via clinical trials.

Attribute	ARA-290 (Cibinetide) Grade BNeuroprotective	Tesamorelin Grade AGrowth Hormone	Retatrutide Grade AMetabolic
Overview
Evidence grade	Grade B	Grade A	Grade A
Category	Neuroprotective	Growth Hormone	Metabolic
Primary focus	Neuropathy, inflammation	Visceral fat, growth hormone axis	Triple GIP/GLP-1/glucagon agonist
Summary	Promising small-molecule peptide for diabetic neuropathy and sarcoidosis-related small fiber neuropathy. Phase II trials show improved nerve fiber density and reduced neuropathic pain without raising hematocrit.	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.	Phase II trial results showed ~24% mean weight loss at 48 weeks at the 12 mg dose — markedly exceeding tirzepatide and prior GLP-1 monotherapies. Currently in Phase III; not yet FDA-approved but expected to be a landmark obesity and metabolic therapy.
Mechanism
Mechanism of action	11-amino-acid peptide derived from erythropoietin's helix B. Binds the innate-repair receptor (a heterodimer of EPOR + βcR) to trigger tissue-protective and anti-inflammatory cascades without activating the hematopoietic EPO receptor.	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.	First-in-class triple agonist of GIP, GLP-1, and glucagon receptors. The GLP-1 and GIP arms drive glucose-dependent insulin secretion and satiety; the glucagon arm increases energy expenditure — producing the largest weight-loss effect of any incretin to date.
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 A — supported by multiple randomised human trials or an approved regulatory indication. Mechanism, dosing and safety are well characterised in humans.	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 injection	Subcutaneous injection
Half-life	~2 minutes systemic (sustained tissue receptor occupancy)	~26 minutes in plasma; the growth hormone rise it triggers persists 4-6 hours	~6 days (supports once-weekly dosing)
PK notes	ARA-290 (Cibinetide) is administered subcutaneous injection with an approximate systemic half-life of ~2 minutes systemic (sustained tissue receptor occupancy). 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. 11-amino-acid peptide derived from erythropoietin's helix B. Binds the innate-repair receptor (a heterodimer of EPOR + βcR) to trigger tissue-protective and anti-inflammatory cascades without activating the hematopoietic EPO receptor.	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.	Retatrutide is administered subcutaneous injection with an approximate systemic half-life of ~6 days (supports once-weekly dosing). Steady-state and tissue-level effects can outlast plasma concentration, which is why dosing frequency (Once weekly) is designed to match receptor kinetics rather than plasma exposure. First-in-class triple agonist of GIP, GLP-1, and glucagon receptors. The GLP-1 and GIP arms drive glucose-dependent insulin secretion and satiety; the glucagon arm increases energy expenditure — producing the largest weight-loss effect of any incretin to date.
Administration
Typical dose	4 mg	2 mg (1.28 mg for the newer F8/WR formulation)	Titrated 2 mg → 4 mg → 8 mg → 12 mg
Frequency	Once daily	Once daily	Once weekly
Cycle length	28 days (typical trial protocol)	26 weeks in the pivotal trials; benefit reverses on stopping	Ongoing; weight regain occurs on cessation
Timing	Morning, subcutaneous (abdominal site)	Bedtime, to sit with the natural overnight GH pulse	Same day each week; any time of day
Protocol steps	Route: Subcutaneous injection. Typical starting dose 4 mg, Once daily. Timing: Morning, subcutaneous (abdominal site) — keep it the same each dosing day to make effects legible. Cycle length: 28 days (typical trial protocol). 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.	Route: Subcutaneous injection. Typical starting dose Titrated 2 mg → 4 mg → 8 mg → 12 mg, Once weekly. Timing: Same day each week; any time of day — keep it the same each dosing day to make effects legible. Cycle length: Ongoing; weight regain occurs on cessation. 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 corneal nerve fiber density in sarcoid neuropathy Reduction in neuropathic pain scores (Phase II) Anti-inflammatory effect without immunosuppression No hematopoietic stimulation (unlike EPO)	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	~24% mean weight loss at 48 weeks (Phase II) Marked improvements in HbA1c, blood pressure, ApoB and liver fat Convenient once-weekly dosing Likely best-in-class cardiometabolic profile
Common stacks	Alpha-lipoic acid, B-complex with methylated B12, Omega-3	Zone 2 cardio, Resistance training, Regular HbA1c and IGF-1 monitoring	Creatine monohydrate, Whey protein, Vitamin D3 + K2
Risks
Side effects	Injection site irritation Mild headache Short-term safety profile favorable in completed trials	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	Nausea, vomiting, diarrhea (especially during titration) Injection site reactions Reduced appetite to the point of inadequate protein intake — pair with resistance training and protein targeting Theoretical pancreatitis and gallbladder risk (class effect)
Contraindications	Active malignancy (limited data) Pregnancy and lactation	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	Personal or family history of medullary thyroid carcinoma Multiple Endocrine Neoplasia type 2 Pregnancy and lactation Prior severe reaction to GLP-1 agonists
Interactions	EPO / ESAs — Mechanistically distinct but caution if combined.	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.	Insulin and sulfonylureas — Risk of hypoglycemia — dose reduction usually required. Oral medications — Delayed gastric emptying may alter absorption; separate timing for narrow-therapeutic-index drugs.
Legal status	Investigational drug; not approved for general human therapeutic use.	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.	Investigational; not yet FDA-approved. Currently available only via clinical trials.

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