Overview

EB618 is an oral tablet formulation of oxyntomodulin (OXM) being developed by Entera Bio for metabolic and fibrotic conditions, including obesity, type 2 diabetes, and metabolic dysfunction-associated steatohepatitis (MASH). Oxyntomodulin is a 37-amino-acid gut peptide co-secreted with GLP-1 by intestinal L-cells after a meal. Unlike pure GLP-1 receptor agonists such as semaglutide, oxyntomodulin activates both the GLP-1 receptor (driving satiety and glycemic control) and the glucagon receptor (driving energy expenditure and potentially better preservation of lean mass during weight loss). Dual GLP-1/glucagon agonism has been a major focus of obesity drug development; injectable dual agonists such as cotadutide and survodutide have shown efficacy in trials. EB618 applies Entera's proprietary tablet excipient platform — the same technology underpinning EB613 and EB612 — to the oxyntomodulin scaffold. As of May 2026 the program is in preclinical development. Non-human primate pharmacokinetic data have been submitted to ENDO 2026.

Mechanism of Action

Oxyntomodulin binds and activates two class B G-protein-coupled receptors: GLP-1R and glucagon receptor (GCGR). GLP-1R activation slows gastric emptying, suppresses appetite via hypothalamic pathways, and enhances glucose-dependent insulin secretion. GCGR activation increases hepatic glucose output and energy expenditure, and may improve hepatic lipid handling — a property of particular interest in MASH. The dual mechanism produces weight loss with a different body-composition signature than pure GLP-1 agonism: theoretically less lean mass loss and better metabolic efficiency. Tuning the GLP-1R/GCGR activation ratio is the core pharmacological design challenge for any OXM-class drug.

Potential Benefits

  • Dual GLP-1/glucagon receptor activation versus single-receptor GLP-1 agonism
  • Potential for better lean mass preservation during weight loss
  • Mechanistic rationale for MASH and fibrotic liver disease beyond pure GLP-1 agents
  • Oral tablet route in a class currently dominated by injectables

Dosage Protocols

The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.

BeginnerInvestigational only — not available outside trial
IntermediateInvestigational only — not available outside trial
AdvancedInvestigational only — not available outside trial
Cycle DurationNot yet defined

EB618 is not commercially available. Patients seeking GLP-1 or dual-agonist metabolic therapy should consult their physician about approved options (semaglutide, tirzepatide, etc.).

Routes of Administration

Oral (tablet) Not publicly disclosed

Oxyntomodulin tablet built on the Entera tablet excipient platform.

Reconstitution

StoragePer trial protocol

No reconstitution required.

Need exact syringe measurements?

Amino Acid Sequence

Native human oxyntomodulin is 37 AA: His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr-Lys-Arg-Asn-Arg-Asn-Asn-Ile-Ala. Specific EB618 analog sequence not publicly disclosed.

Side Effects & Safety

  • Preclinical only — human safety profile not characterized
  • GLP-1 class effects expected: nausea, vomiting, delayed gastric emptying
  • Glucagon agonism may increase hepatic glucose output and could raise fasting glucose in some patients — the design challenge is balancing the two arms

Safety & Contraindications

This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.

Absolute

Investigational only

FDA Safety Information

Investigational. No human safety data publicly available as of May 2026.

FDA Source: Bulk Drug Substances Safety Risks

Pharmacokinetics

Half-LifeNative oxyntomodulin half-life is approximately 12 minutes due to rapid DPP-4 cleavage; long-acting OXM analogs are engineered for resistance to DPP-4 and extended half-life. EB618 PK parameters not publicly disclosed.
StoragePer clinical trial protocol

Synergistic Compounds

The following compounds have been studied alongside EB618 (Oral Oxyntomodulin Tablet) for potential complementary or synergistic effects:

Lifestyle modification (diet, resistance training)

Learn More

References & Further Reading