Metabolic/Weight

Ecnoglutide

Research Reagent · Laboratory Use Only

Quick Answer

What do Phase 3 clinical trials show about ecnoglutide for weight loss and diabetes?

Ecnoglutide is a cAMP-biased GLP-1 receptor agonist. In the Phase 3 SLIMMER trial (Lancet Diabetes & Endocrinology, 2025) in 664 Chinese adults with obesity without diabetes, once-weekly subcutaneous ecnoglutide 2.4 mg produced 13.2% mean body weight reduction at 40 weeks versus 0.1% with placebo, with 87% achieving ≥5% weight loss. In type 2 diabetes, the EECOH-1 trial (Nature Communications, 2026) demonstrated HbA1c reductions of up to 2.43% versus 0.87% placebo. Multiple Phase 3 trials have been completed across obesity and diabetes indications.

PMID40555243↗DOI10.1016/S2213-8587(25)00141-X↗⟳ Reconstitution Calculator
Scientific AbstractPMID 40555243 · 2025

Background

Ecnoglutide (XW004) is a novel cyclic adenosine monophosphate (cAMP)-biased GLP-1 receptor agonist developed by Sciwind Biosciences. The SLIMMER Phase 3 trial (NCT05813795) enrolled 664 Chinese adults with overweight or obesity (BMI ≥28 or ≥24 with comorbidity), without diabetes, randomised to once-weekly subcutaneous ecnoglutide 1.2, 1.8, or 2.4 mg or placebo for 40 weeks at 36 centres.

Results

Least-squares mean body weight change at week 40 was −9.1%, −10.9%, and −13.2% with ecnoglutide 1.2, 1.8, and 2.4 mg respectively vs +0.1% placebo (all p<0.0001). Proportion achieving ≥5% weight loss: 77%, 84%, and 87% vs 16% with placebo. At week 48 with 2.4 mg, mean weight loss reached 15.4%. GI adverse events (mild-to-moderate) were the most common. EECOH-1 Phase 3 (NCT05680155, Nature Communications Jan 2026, DOI 10.1038/s41467-025-68165-7): ecnoglutide 1.2 mg and 1.2 mg monotherapy demonstrated HbA1c reductions of −1.96% and −2.43% vs −0.87% placebo at 24 weeks in type 2 diabetes. EECOH-2 Phase 3 (PMID 40854315, Lancet Diabetes Endocrinol Oct 2025): ecnoglutide non-inferior to dulaglutide in T2D over 52 weeks.

Source:10.1016/S2213-8587(25)00141-X
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Ecnoglutide?

Ecnoglutide (XW004, oral form XW003) is an investigational cAMP-biased GLP-1 receptor agonist developed by Hangzhou Sciwind Biosciences for the treatment of obesity and type 2 diabetes. It is the first GLP-1 receptor agonist to utilise a biased signalling approach — selectively activating the cAMP pathway over the β-arrestin pathway — which may improve sustained receptor activity and reduce gastrointestinal adverse events compared to unbiased GLP-1 receptor agonists.

Mechanism of Action

Ecnoglutide is a long-acting, acylated GLP-1 analogue that selectively engages Gs-protein/cAMP signalling at the GLP-1 receptor while showing reduced β-arrestin recruitment compared to semaglutide. This "biased agonism" is hypothesised to prolong receptor activation, reduce receptor internalisation and desensitisation, and potentially improve the tolerability profile. Like other GLP-1 receptor agonists, ecnoglutide suppresses appetite, slows gastric emptying, and enhances glucose-dependent insulin secretion. An oral tablet formulation (XW004) is also in development and has completed Phase 1 trials.

Observed Clinical Results

  • Phase 3 SLIMMER (NCT05813795, Lancet Diabetes Endocrinol Sep 2025): Once-weekly ecnoglutide 2.4 mg produced −13.2% mean body weight at week 40 vs +0.1% placebo; 87% of participants achieved ≥5% weight loss. At 48 weeks, 2.4 mg arm achieved 15.4% weight loss with 92.8% achieving ≥5% reduction.
  • Phase 3 EECOH-1 (NCT05680155, Nature Comms Jan 2026): In T2D, HbA1c reduction −2.43% with 1.2 mg vs −0.87% placebo at 24 weeks.
  • Phase 3 EECOH-2 (Lancet Diabetes Endocrinol Oct 2025): Non-inferior to dulaglutide in T2D at 52 weeks.
  • Phase 1 oral XW004: 6.8% weight loss at 6 weeks with up to 30 mg/day in healthy obese participants.

Regulatory Status

  • Multiple Phase 3 trials completed in China
  • Global development in progress
  • No FDA or EMA approval as of 2026
Clinical Research Parameters
2 trials2 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT05813795 ↗
COMPLETEDPhase IIIn=664

A Phase 3 Study of Ecnoglutide in Adults With Overweight or Obesity (SLIMMER)

SLIMMER was a Phase 3, randomised, double-blind, placebo-controlled trial at 36 centres in China evaluating once-weekly subcutaneous ecnoglutide 1.2, 1.8, and 2.4 mg versus placebo in 664 adults with overweight or obesity without diabetes over 40 weeks (primary endpoint) with 48-week efficacy assessment. Results published in Lancet Diabetes & Endocrinology (September 2025, PMID 40555243): least-squares mean body weight change at week 40 was −9.1%, −10.9%, −13.2% at 1.2, 1.8, 2.4 mg versus +0.1% placebo (all p<0.0001). Proportion achieving ≥5% weight loss: 77%, 84%, 87% vs 16% placebo. At 48 weeks, the 2.4 mg dose achieved 15.4% mean weight loss with 92.8% achieving ≥5% reduction.

Study Interventions
Ecnoglutide 1.2 mg, Ecnoglutide 1.8 mg, Ecnoglutide 2.4 mg, Placebo
Primary Endpoints
Percentage change in body weight at week 40; Proportion achieving ≥5% body weight reduction at week 40
Study Period
2023-04 → 2024-11
NCT05680155 ↗
COMPLETEDPhase IIIn=211

A Phase 3 Study of Ecnoglutide in Patients With Type 2 Diabetes (EECOH-1)

EECOH-1 was a Phase 3, multicentre, randomised, double-blind, placebo-controlled trial in 211 adults with type 2 diabetes inadequately controlled on diet/exercise or a single oral hypoglycaemic agent. Participants were randomised to once-weekly ecnoglutide 0.6 mg or 1.2 mg or placebo for 24 weeks at 32 Chinese centres. Results published in Nature Communications (January 2026, DOI 10.1038/s41467-025-68165-7): HbA1c changed by −1.96% (0.6 mg), −2.43% (1.2 mg), and −0.87% (placebo) at week 24. The cAMP-biased mechanism of ecnoglutide demonstrated efficacy consistent with approved GLP-1 receptor agonists.

Study Interventions
Ecnoglutide 0.6 mg, Ecnoglutide 1.2 mg, Placebo
Primary Endpoints
Change in HbA1c from baseline at week 24
Study Period
2022-12 → 2024-06
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Ecnoglutide is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 40555243) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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