MBX 5765

What is MBX 5765?

MBX 5765 is MBX Biosciences' investigational prodrug version of the parent unimolecular dual GLP-1 and amylin receptor agonist originally developed by Novo Nordisk as amycretin — assigned the International Nonproprietary Name zenagamtide in 2026. Zenagamtide (formerly amycretin) combines amylin agonism (via the calcitonin receptor / RAMP1-3 complexes) and GLP-1 receptor agonism in a single molecule, producing additive satiety, gastric-emptying, and glucagon-suppression effects. Mora and colleagues published two Phase 2 zenagamtide trials in Lancet on August 15, 2026 — a once-weekly subcutaneous formulation (PMID 42532080) and a once-daily oral formulation (PMID 42532079) — the first peer-reviewed Phase 2 evidence for the parent scaffold. The MBX 5765 prodrug engineering aims to produce extended pharmacokinetics relative to zenagamtide itself, potentially supporting less-frequent dosing intervals. As of mid-2026, MBX 5765 is in Phase 1 with no direct peer-reviewed clinical publication; the molecule is positioned within MBX's broader portfolio of GLP-1-axis peptide engineering.

What MBX 5765 Is Investigated For

MBX 5765 is an early-stage prodrug version of zenagamtide (formerly amycretin), designed to provide extended pharmacokinetics. The mechanism (amylin plus GLP-1 dual receptor agonism) is biologically well-characterized: amylin agonism complements GLP-1 agonism through largely independent central appetite circuits, producing additive satiety effects beyond either pathway alone. The CagriSema (cagrilintide + semaglutide) precedent suggests dual amylin/GLP-1 activation can produce 22.7% weight loss at 68 weeks, and the parent zenagamtide Phase 2 trials in T2D (Mora et al., Lancet 2026, PMIDs 42532079 and 42532080 for oral and SC formulations respectively) provide the first peer-reviewed unimolecular dual-agonist Phase 2 evidence base that MBX 5765 will need to build on. The honest caveats: MBX 5765 is Phase 1 with no direct publications, and the competitive landscape is increasingly dense — zenagamtide/amycretin from Novo Nordisk, eloralintide, petrelintide, and combination amylin-GLP-1 strategies are all in active development. Alhazmi 2026 Diabetes Obes Metab (PMID 42452898) reviews the amylin-analog class as the next major weight-loss category, and Fischer 2026 Pharmacol Res (PMID 42586227) frames amylin-based pharmacotherapy as the leading GLP-1-adjacent strategy for better-tolerated weight-loss drugs.

History & Discovery

Amycretin was originally developed by Novo Nordisk as a single-peptide amylin and GLP-1 dual agonist alternative to combination cagrilintide + semaglutide. It was assigned the International Nonproprietary Name zenagamtide in 2026, following the standard developer-code-to-INN progression ahead of regulatory review. Peer-reviewed Phase 2 evidence for the parent scaffold read out on August 15, 2026: Mora and colleagues published dose-finding Phase 2 trials of both once-weekly subcutaneous zenagamtide (Lancet, PMID 42532080) and once-daily oral zenagamtide (Lancet, PMID 42532079) in type 2 diabetes patients. MBX 5765 is MBX Biosciences' prodrug engineering applied to the zenagamtide scaffold, producing an extended-action variant. Development is at Phase 1 stage as of mid-2026, with the broader amylin-analog class positioned as the next major weight-loss category (Alhazmi 2026 Diabetes Obes Metab; Fischer 2026 Pharmacol Res).

How It Works

Two appetite hormones (amylin and GLP-1) work together to help you feel full and eat less. MBX 5765 is a slow-release version of amycretin — a single peptide that activates both receptors at once, designed to give a longer-lasting effect from each dose.

Zenagamtide (formerly amycretin, and by extension MBX 5765) binds both the amylin receptor complex (calcitonin receptor with RAMP1-3) and the GLP-1 receptor as a unimolecular dual agonist. Amylin agonism activates the area postrema in the brainstem and downstream central anorectic circuits, slows gastric emptying, and suppresses postprandial glucagon. GLP-1 agonism activates hypothalamic appetite-regulating circuits, slows gastric emptying through a partially overlapping mechanism, and enhances glucose-dependent insulin secretion. The combined dual receptor agonism produces additive effects — amylin and GLP-1 act on distinct but complementary central appetite circuits. The MBX 5765 prodrug strategy adds engineered chemistry to the zenagamtide backbone, intended to produce extended pharmacokinetic profile while preserving the dual receptor engagement. Phase 2 evidence for the parent scaffold is now indexed in the peer-reviewed literature — Mora et al. Lancet 2026 reported dose-finding Phase 2 trials of both once-weekly SC (PMID 42532080) and once-daily oral (PMID 42532079) zenagamtide in type 2 diabetes, establishing the pharmacology, dose-response, and safety-tolerability envelope MBX 5765's prodrug engineering will need to compete against on convenience and pharmacokinetic profile.

Evidence Snapshot

Research Gaps & Open Questions

What the current literature has not yet settled about MBX 5765:

• 01Phase 1 efficacy and safety — pending.
• 02Comparison versus parent amycretin and versus CagriSema.
• 03Long-term safety.

Forms & Administration

Subcutaneous injection — extended interval anticipated.

Dosing & Protocols

The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.

Investigational.

Timeline of Effects

Common Questions

Who MBX 5765 Is NOT For

Drug & Supplement Interactions

Class-level GLP-1 and amylin interaction considerations apply — slowed gastric emptying may affect concurrent oral drug absorption.

Safety Profile

Legal Status

Regulatory status changes over time. Verify current local rules with a qualified professional.

Myths & Misconceptions