Metabolic Small Molecule

O-304

Also called ATX-304 • Pan-AMPK Activator • Metabolic Research

O-304 is an orally active small molecule developed to activate the AMPK network and increase metabolic demand. It is not a peptide. Early human studies report changes in glucose handling, lipid metabolism, body composition, vascular function, and resting metabolic rate, but the clinical formulations are not automatically equivalent to grey-market O-304 capsules.

AMPK Activation Energy Expenditure Glucose Handling Vascular Research

Protocol Snapshot

Quick reference before the deep dive

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O-304

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Community Start

50mg

Oral, typically in the morning. Not a clinically validated starting dose.

Published ATX-304

400mg

Once daily for 8 weeks in the 2026 Phase 1b study.

Route

Oral

Small-molecule capsule, powder, or clinical tablet—not an injectable peptide.

Legacy Trial

1000mg

Daily for 28 days in adults with type 2 diabetes taking metformin.

Peptide Grade

GradeB

The metabolic signal is real: human trials show higher resting energy expenditure alongside improvements in visceral fat, liver fat, glucose control, triglycerides, and adiponectin—without relying on appetite suppression. The limitation is practical confidence: studies are still short, community experience is limited, and grey-market capsules may not match the clinically tested ATX-304 formulation.

Research Community Safety

Foundation

Research context, mechanisms, and practical use cases

What Is O-304?

O-304 is an orally bioavailable small molecule developed as a pan-activator of AMP-activated protein kinase, or AMPK. AMPK is a cellular energy sensor that helps coordinate glucose uptake, fatty-acid oxidation, mitochondrial activity, and other responses to low-energy conditions such as exercise or caloric restriction.

Unlike many direct AMPK activators, O-304 was designed to increase phosphorylated AMPK by slowing its dephosphorylation rather than depleting cellular ATP. Later research also identified a mitochondrial-uncoupling component that increases metabolic demand and may help explain why glucose taken into muscle is used rather than simply stored as glycogen.

O-304 vs. ATX-304

O-304 is the earlier development name and formulation studied in the 2018 TELLUS trial. ATX-304 is the current clinical-development name and uses a newer sodium-salt tablet formulation with improved exposure. They share the same development lineage, but dose-for-dose equivalence should not be assumed.

That distinction matters in the grey market. A capsule labeled O-304 or ATX-304 does not automatically match the identity, bioavailability, or quality of either clinical formulation.

O-304 Benefits

The strongest evidence is short-term human metabolic data, supported by animal and cellular studies. O-304 is not approved to treat diabetes, obesity, cardiovascular disease, or any other condition.

Resting Metabolic Rate

In a 2026 Phase 1b study, 400mg ATX-304 once daily increased resting metabolic rate by 8% after eight weeks.

Visceral and Liver Fat

The same small study reported significant reductions in visceral adipose tissue and liver fat, with minimal total weight loss at that exposure.

Glucose Control

The 28-day TELLUS trial found lower fasting plasma glucose within the O-304 group and an improvement in HOMA-IR, although not every comparison versus placebo was significant.

Lipid Metabolism

Phase 1b results reported lower triglycerides and higher adiponectin, supporting a measurable effect on lipid handling.

Blood Pressure and Perfusion

Legacy O-304 improved calf-muscle microvascular perfusion and reduced blood pressure in adults with type 2 diabetes.

Exercise-Mimetic Research

Animal studies show increased energy expenditure, glucose utilization, exercise capacity, and cardiac function. These outcomes are not yet established in humans.

Evidence Reality Check

The published human evidence remains small: 65 adults were randomized in the 28-day TELLUS study, and 23 adults with obesity and prediabetes entered the 2026 Phase 1b study. The results are promising, but they do not establish long-term safety, durable weight loss, or a general-use protocol.

Mechanism of Action

Pan-AMPK Activation

O-304 increases phosphorylated AMPK across AMPK complexes by suppressing dephosphorylation.

Metabolic Demand

Its mitochondrial-uncoupling activity creates energy demand, increasing substrate use and whole-body energy expenditure.

Muscle Glucose Utilization

Preclinical work shows insulin-independent glucose uptake and oxidation in skeletal muscle and heart without excess glycogen accumulation.

Peripheral Restriction

The current ATX-304 program is designed to act mainly outside the central nervous system, differentiating it from appetite-suppressing drugs.

Protocol Planning

Dosing, formulation, and research duration

O-304 Dosing Protocol

Current Human Research

Compound

ATX-304 sodium-salt tablet

Dose

400mg once daily

Duration

8 weeks, followed by an optional 8-week open-label extension

Population

Adults with obesity and prediabetes

Important

This dose belongs to the validated clinical tablet and should not be transferred directly to an unverified capsule or powder

Legacy O-304 Research

Dose

1000mg daily

Duration

28 days

Population

Adults with type 2 diabetes taking metformin

Formulation

Earlier O-304 clinical suspension

Important

The 1000mg trial dose is not a target for grey-market experimentation

Oral Route and Grey-Market Context

Community Entry

50mg in the Morning

Community reports commonly begin around 50mg once daily and sometimes move toward 100–150mg daily. This range is anecdotal, not clinically validated, and product identity is a major variable.

Timing

Earlier in the Day

Morning use makes tracking energy, body temperature, glucose, heart rate, and sleep disruption easier. Published clinical reports do not establish a special fasted-use requirement.

Duration

Do Not Extrapolate Indefinitely

Human safety data currently covers 28 days with legacy O-304 and eight to sixteen weeks with the newer ATX-304 program. Continuous long-term use has not been established.

Formulation Is Part of the Dose

The current 400mg clinical result used a sodium-salt tablet with characterized pharmacokinetics. A 50mg research capsule may differ in chemical form, purity, enteric protection, and bioavailability, so milligrams alone cannot prove equivalence.

Anecdotal Data Points

Community-reported outcomes and recurring patterns

Self-reported anecdotal experiences aggregated from public & private peptide community discussions and anonymous peptideprotocols.app user reports. This information does not carry the same weight as published research.

Positive Reports

Some users describe better endurance, warmer body temperature, or a subtle increase in daily energy rather than stimulant-like drive.
Early reports often describe O-304 as more noticeable during cardio or calorie-restricted phases than during sedentary use.
A small number of users with glucose meters report lower post-meal or fasting readings, but uncontrolled single-person readings cannot establish causation.
Appetite suppression is generally not the primary reported effect, which fits its peripheral metabolic mechanism.

Negative Reports

Many users report effects that are subtle or difficult to separate from diet, training, caffeine, GLP-1 drugs, or other metabolic compounds.
GI discomfort has been reported as doses rise.
Isolated reports describe tingling, burning, or neuropathy-like sensations; this is not an established trial signal but warrants stopping and reassessing.
Conflicting labels—O-304, ATX-304, and OS-01—create substantial uncertainty about chemical form and actual exposure.

Stacking & Synergy

Potential O-304 pairings and tracking context

No human O-304 combination protocol has been validated. Because this compound can alter glucose handling, blood pressure, lipid metabolism, and energy expenditure, introduce it alone before considering any mechanistic pairing.

O-304 + GLP-1 Agonists

Animal research suggests complementary fat-loss mechanisms, but human combination efficacy and tolerability are unknown. Appetite suppression can also hide inadequate food intake.

O-304 + MOTS-c

Both converge on AMPK and metabolic signaling. The overlap may be redundant and makes side-effect attribution harder rather than automatically producing synergy.

O-304 + SS-31

SS-31 targets mitochondrial membrane function while O-304 increases metabolic demand. This pairing is mechanistic only and has not been tested clinically.

O-304 + Training

Resistance training, cardio, adequate protein, and sufficient calories provide the clearest context for evaluating changes in endurance, body composition, and recovery.

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Track in Journal

O-304 is best judged with objective metabolic and cardiovascular markers because subjective energy can be subtle and confounded by other compounds.

Dose, product form, vendor, timing, and cycle day.
Fasting and post-meal glucose when appropriate.
Blood pressure, resting heart rate, and body temperature.
Weight, waist, training performance, sleep, and GI response.

Start Tracking

Safety Notes

Side effects, contraindications, and precautions

O-304 Side Effects

Short-term clinical tolerability is encouraging. In the 2026 Phase 1b study, treatment-emergent adverse events were predominantly mild and occurred at a frequency similar to placebo. Continuous monitoring did not show an increase in core body temperature or 24-hour heart rate, and no mitochondrial-failure signal was reported. The earlier O-304 program also reported mostly mild adverse events without clinically significant ECG, vital-sign, examination, or laboratory abnormalities.

These studies were small and short. They do not establish safety for indefinite use, higher exposure, unverified products, or multi-compound grey-market stacks.

Monitor Closely

GI discomfort, nausea, or appetite changes.
Unexpected glucose lowering, especially with diabetes medication.
Lightheadedness or low blood pressure.
Sleep disruption, unusual warmth, or exercise intolerance.

Stop and Reassess

Persistent tingling, burning, numbness, or neuropathy-like symptoms.
Rapid or irregular heartbeat, chest discomfort, or fainting.
Persistent feverish feeling or abnormal body-temperature elevation.
Severe GI symptoms or inability to maintain hydration and nutrition.

O-304 Contraindications and Precautions

Do Not Use If You Have

Pregnancy or breastfeeding, because reproductive and developmental safety has not been established.
An unidentified or unverified product with no credible identity and purity testing.
An acute metabolic, cardiovascular, liver, or kidney illness that requires medical evaluation.

Use Caution With

Insulin, metformin, GLP-1 agonists, SGLT2 inhibitors, or other glucose-lowering drugs.
Blood-pressure medication or a history of hypotension.
Other AMPK activators, mitochondrial uncouplers, stimulants, or aggressive fat-loss stacks.
Neuropathy, unexplained tingling, arrhythmia, or impaired temperature regulation.

Regulatory Status

O-304 and ATX-304 are investigational compounds and are not FDA approved for human use. The current ATX-304 program is entering Phase 2 development; grey-market capsules are not approved clinical products.

FINAL VERDICT

Peptide Protocol's Opinionated Opinion

This is not medical advice. This editorial is our own opinion piece based off the experience of our own lab rats.

We see O-304 as one of the more interesting mitochondrial uncouplers and exercise mimetics in the space. It’s designed to boost energy expenditure, improve insulin sensitivity, and mimic some of the benefits of exercise without actually training. Some users report better endurance, fat loss, and metabolic flexibility, especially when stacked with compounds like Retatrutide or MOTS-c.

From our testing and community feedback, it has potential but is still early-stage. Results are noticeable for some—particularly those with metabolic sluggishness—but others see minimal effects or mild GI discomfort. It’s not a magic pill; it works best when paired with actual training and a solid diet. We like it as a targeted tool rather than an everyday staple.

Overall, O-304 is worth experimenting with if mitochondrial efficiency and metabolic rate are bottlenecks for you. It’s not as proven or dramatic as some of the top-tier peptides, but it has a unique mechanism that makes it intriguing for advanced stacks. We keep it on the radar for recomp and longevity protocols, but we don’t consider it essential for everyone. Solid niche player.