Ecnoglutide

A once-weekly cAMP-biased GLP-1 receptor agonist peptide from Sciwind Biosciences, approved in China in 2026 for type 2 diabetes and chronic weight management, with a United States phase 2 program for an oral tablet and no FDA approval.

Also referenced as: XW003, XW-003

Also appears in: Metabolic

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What is Ecnoglutide?

Ecnoglutide (development code XW003) is a synthetic analog of human glucagon-like peptide-1 (GLP-1) developed by Hangzhou Sciwind Biosciences. It carries an alanine-to-valine substitution at position 8, which protects the peptide from the enzyme DPP-4, and a C18 fatty diacid attached through a γ-glutamate and double AEEA linker, which binds albumin and extends the half-life at steady state to 124 to 138 hours, long enough for once-weekly subcutaneous injection (Guo et al., Molecular Metabolism, 2023;75:101762). Its distinguishing feature is signaling bias: it drives cAMP production at the GLP-1 receptor without measurable receptor internalization, a property the developer argues preserves receptor availability and may improve the balance of efficacy and tolerability.

Its first approvals anywhere came in China, where the National Medical Products Administration cleared it in January 2026 for glycemic control in adults with type 2 diabetes and in March 2026 for long-term weight management (Shirley, Drugs, 2026;86(9):1563–1570). It has drawn interest outside China because its phase 3 weight loss sits in the range reported for other once-weekly GLP-1 agonists and because an oral tablet of the same peptide is being tested in the United States. It appears in some research-peptide catalogs under its nonproprietary name or development code.

How it works

• Full GLP-1 receptor agonism with a cAMP bias. In cell assays ecnoglutide stimulated cAMP with an EC50 of 0.018 nM, while the concentration needed for GLP-1 receptor internalization exceeded 10 μM, which the authors read as a signaling bias (Guo et al., Molecular Metabolism, 2023;75:101762). Reduced internalization and β-arrestin recruitment are hypothesized to limit receptor desensitization during chronic dosing, although the clinical contribution of the bias has not been isolated from the effects of dose and exposure.
• Albumin binding for weekly exposure. The C18 diacid side chain binds serum albumin, slowing clearance and producing a steady-state half-life of about five to six days in humans (Guo et al., Molecular Metabolism, 2023). In diet-induced obese rats and db/db mice the compound lowered glucose, promoted insulin secretion and produced a more pronounced reduction in body weight than semaglutide.
• Downstream incretin pharmacology. Like other GLP-1 receptor agonists, ecnoglutide increases glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying and reduces appetite through hypothalamic and hindbrain circuits, the actions that produce both HbA1c lowering and weight loss in this class (Drucker, Cell Metabolism, 2018;27(4):740–756).

Research status

Phase 1 (NCT04389775). A first-in-human study in 64 healthy adults in Australia, run from March 2020 to September 2021, tested single doses of 0.03 to 1.0 mg and six weeks of weekly dosing at 0.2 to 0.6 mg. The most common adverse events were decreased appetite, nausea and headache (Guo et al., Molecular Metabolism, 2023).

Phase 2 in obesity (NCT05111912). An open-label, randomized, dose-finding trial in 206 adults with obesity in Australia compared weekly ecnoglutide with daily liraglutide 3.0 mg, and completed in December 2022. No results have been posted to ClinicalTrials.gov and the trial has not been published in a peer-reviewed journal, so the only weight-loss figures in circulation come from sponsor conference materials.

Phase 2 in type 2 diabetes (CTR20211014). In a 20-week, placebo-controlled trial in 145 Chinese adults with type 2 diabetes, once-weekly doses of 0.4, 0.8 and 1.2 mg lowered HbA1c by 1.81, 1.90 and 2.39 percentage points versus 0.55 for placebo (p<0.0001), 71.9% of the 1.2 mg group reached HbA1c of 6.5% or lower versus 9.1% on placebo, and 33.3% lost at least 5% of body weight versus 3.0% on placebo (Zhu et al., Nature Communications, 2024;15(1):8408).

SLIMMER, phase 3 in overweight or obesity (NCT05813795). A randomized, double-blind, placebo-controlled trial at 36 centers in China enrolled 664 adults with overweight or obesity and without diabetes, randomized 3:3:3:1:1:1 to weekly ecnoglutide 1.2, 1.8 or 2.4 mg or volume-matched placebo. At week 40 the least-squares mean body weight change was −9.1%, −10.9% and −13.2% versus 0.1% for placebo, and 77%, 84% and 87% of treated participants lost at least 5% of body weight versus 16% on placebo (all p<0.0001). Treatment-emergent adverse events occurred in 93% of each ecnoglutide group and 84% of the placebo group, mostly mild-to-moderate gastrointestinal events, and ten ecnoglutide-treated participants discontinued because of adverse events (Ji et al., Lancet Diabetes & Endocrinology, 2025;13(9):777–789).

EECOH-1, phase 3 monotherapy in type 2 diabetes (NCT05680155). A double-blind, placebo-controlled trial at 32 Chinese centers randomized 211 adults inadequately controlled on diet and exercise alone or with a single oral agent to weekly ecnoglutide 0.6 mg, 1.2 mg or volume-matched placebo for 24 weeks. HbA1c fell by 1.96 and 2.43 percentage points versus 0.87 on placebo (differences −1.09, p=0.0003, and −1.56, p<0.0001) (Zhu et al., Nature Communications, 2026;17(1):1420).

EECOH-2, phase 3 versus dulaglutide (NCT05680129). A 52-week, open-label, active-controlled non-inferiority trial at 52 Chinese hospitals randomized 623 adults with type 2 diabetes and elevated glucose on metformin monotherapy to ecnoglutide 0.6 mg, ecnoglutide 1.2 mg or dulaglutide 1.5 mg weekly. At week 32 HbA1c fell by 1.91, 1.89 and 1.65 percentage points; both doses met the 0.4-point non-inferiority margin and the 1.2 mg dose was statistically superior (difference −0.24, 95% CI −0.38 to −0.11, p=0.0002), a difference the authors judged not clinically relevant, and reductions were sustained to week 52. Discontinuations for adverse events were 3%, 4% and 3% (He et al., Lancet Diabetes & Endocrinology, 2025;13(10):863–873). An accompanying commentary weighed the drug’s place among existing GLP-1 agonists (Scheen, Lancet Diabetes & Endocrinology, 2025;13(10):818–820).

SLIMMER-UP-SWITCH, phase 2 versus semaglutide (NCT07073417). An open-label treatment-switching trial in China enrolled 163 adults with obesity and compares ecnoglutide with semaglutide. It began July 28, 2025, is active and no longer recruiting, and its primary completion is estimated for February 2027. No results have been posted, and the interim comparison that has circulated from a June 2026 conference presentation is sponsor-reported and unpublished.

Chinese approvals. The National Medical Products Administration approved ecnoglutide injection in January 2026 for glycemic control in adults with type 2 diabetes and in March 2026 for long-term weight management, in combination with diet control and increased physical activity, in adults with obesity or with overweight and at least one weight-related comorbidity (Shirley, Drugs, 2026). Further Chinese phase 3 trials opened in 2026 in adults with obesity and obstructive sleep apnea, both without and with positive airway pressure therapy (NCT07387094, recruiting from February 9, 2026; NCT07434050, recruiting from March 2, 2026), and in adults with obesity and knee osteoarthritis (NCT07734311, recruiting from August 3, 2026). A phase 3 trial in Chinese adolescents with obesity (SLIMMER-YOUNG, NCT07836270) is registered and not yet recruiting, following a completed 48-participant adolescent pharmacokinetic study (NCT07143227).

Oral tablet and the United States program. Sciwind’s oral formulation of the same peptide (XW004), which pairs the peptide with an absorption enhancer, completed a phase 1 study in Australia (NCT05184322) and entered a phase 1b/2a study in Chinese adults with overweight or obesity on November 18, 2025 (NCT07243171). Verdiva Bio develops the weekly oral tablet as VRB-101 under license from Sciwind. Verdiva’s EVOLVE-2 (NCT07281937), a randomized, double-blind, placebo-controlled phase 2b trial in 206 adults with obesity or overweight and weight-related comorbidities, ran at 22 United States sites under FDA investigational-drug regulation from November 25, 2025 to July 23, 2026; no results had been released as of November 2026. A second United States phase 2 study of VRB-101 as a maintenance therapy (NCT07553299) was stopped in September 2026 after enrolling eight participants, the sponsor citing a business decision rather than safety findings. No phase 3 trial of either the injection or the tablet is registered outside China, and neither is approved in the United States or Europe.

Common dosage forms

• Subcutaneous injection. The presentation approved in China for adults with type 2 diabetes and for chronic weight management, dispensed on prescription. The device format of the marketed product has not been described in English-language regulatory or company sources.
• Investigational oral tablet. XW004 / VRB-101, supplied only to clinical-trial sites in China, Australia and the United States.
• No approved or compounded product exists in the United States. Ecnoglutide is not an FDA-approved active ingredient, so it cannot be legally compounded in the United States; the only non-trial presentation outside China is lyophilized powder in research vials labeled for laboratory use.

Key considerations

• Regulatory status. The Investigational status reflects an active, FDA-regulated United States development program for the oral tablet, whose phase 2b trial completed in July 2026, alongside Chinese marketing approvals for type 2 diabetes (January 2026) and chronic weight management (March 2026) and no approval in the United States or Europe as of November 2026.
• Evidence gaps. The peer-reviewed phase 3 evidence comes entirely from trials in Chinese adults, each funded and run by the developer, with the longest placebo-controlled weight-loss data at 40 weeks. There is no cardiovascular outcomes trial, no published head-to-head comparison with semaglutide or tirzepatide, no peer-reviewed data for the oral tablet and no published data from outside China. Whether the cAMP bias translates into any clinical advantage over conventional GLP-1 agonists is unproven.
• Safety signals. Adverse events track the GLP-1 class: nausea, vomiting, diarrhea and decreased appetite, mostly during dose escalation, with treatment-emergent events in 93% of ecnoglutide-treated participants in SLIMMER and adverse-event discontinuations of 2% to 4% across the phase 3 trials. The trials were too small and short to characterize pancreatitis, gallbladder disease, retinopathy progression, thyroid C-cell effects, lean-mass loss or weight regain after stopping, and none of these risks has been shown to differ from approved agents.
• Naming. Ecnoglutide, XW003 and XW-003 refer to the injectable peptide; XW004 and VRB-101 are codes for the oral tablet of the same molecule, not a different compound. The compound is marketed in China under a Chinese-language brand name, no brand name has been announced in English-language sources, and no United States pharmacopeial or FDA reference standard exists. Semaglutide and liraglutide share its fatty-acid acylation strategy but not its biased-signaling profile.