Ecnoglutide
Ecnoglutide (XW003); modified GLP-1(7-37) peptide with Ala8Val substitution and gamma-Glu-2xAEEA-linked C18 diacid fatty acid at Lys30
A novel cAMP-biased GLP-1 receptor agonist developed by Sciwind Biosciences, approved by China's NMPA for adult type 2 diabetes (January 2026) and chronic weight management (March 2026), with Phase 3 trials showing up to 13.2% body weight loss at 40 weeks (PMID 40555243) and HbA1c reductions of up to 2.43% in T2DM (PMID 41501026).
Last updated: 2026-03-10
Safety Summary
Across Phase 2 and Phase 3 injectable studies, most adverse events were transient mild-to-moderate gastrointestinal events. In Phase 2 (n=145), ecnoglutide-treated participants had diarrhea in 14.7%, nausea in 11.9%, constipation in 7.3%, decreased appetite in 6.4%, lipase increase in 5.5%, and hypoglycemia in 5.5% (mild, non-dose-dependent, mainly due to skipped meals), with no treatment-related grade 3 or higher adverse events and no treatment-related serious adverse events (PMID 39333121). In EECOH-1 (Phase 3, n=211), TEAEs occurred in 78.3% (0.6 mg) and 77.5% (1.2 mg) vs. 63.4% placebo; no severe hypoglycemia, pancreatitis, or gallbladder-related disorders were reported (PMID 41501026). In EECOH-2 (Phase 3, n=621), discontinuation due to adverse events was 3% (ecnoglutide 0.6 mg), 4% (1.2 mg), and 3% (dulaglutide) over 52 weeks (PMID 40854315). In the SLIMMER obesity trial (Phase 3, n=664), TEAEs occurred in 93% of ecnoglutide-treated participants vs. 84% placebo; 10 ecnoglutide-treated participants discontinued due to adverse events; most common AEs were mild-to-moderate gastrointestinal events (PMID 40555243). In Phase 1, adverse events included decreased appetite, nausea, and headache (PMID 37364710). No signal of pancreatitis, severe hypoglycemia, or thyroid C-cell pathology has emerged across the clinical program.
Known Side Effects
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Who Should NOT Use This
GLP-1 receptor agonists carry a class-wide concern for thyroid C-cell tumor risk observed in rodents. Standard contraindication for all approved GLP-1 agonists (PMID 38343381). These histories were among key exclusions in ecnoglutide Phase 2 trials (PMID 39333121).
Class-wide GLP-1 agonist contraindication due to MTC risk (PMID 38343381). Excluded from ecnoglutide clinical trials (PMID 39333121).
GLP-1 class concern. Pancreatitis was an exclusion criterion in Phase 2 (PMID 39333121). No pancreatitis cases were reported in ecnoglutide trials (PMID 41501026), but caution applies per class.
GLP-1 agonists slow gastric emptying and may worsen gastroparesis. Class effect applicable to ecnoglutide.
Increased hypoglycemia risk when combined. Dose adjustment may be needed. Risk is low as monotherapy due to glucose-dependent mechanism. Phase 2 mild hypoglycemia was associated with skipped meals, not dose-dependent (PMID 39333121).
Published trials enrolled non-pregnant, non-lactating adults and required contraception (PMID 39333121). Clinical safety during pregnancy or breastfeeding is not established. GLP-1 agonists are generally not recommended in pregnancy.
Talk to Your Doctor
Before considering Ecnoglutide, discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-17]
Evidence Assessment
Tier 2 -- Multiple completed Phase 3 RCTs with positive results. EECOH-1 (Phase 3, n=211, T2DM, PMID 41501026), EECOH-2 (Phase 3, n=621, T2DM vs. dulaglutide, PMID 40854315), and SLIMMER (Phase 3, n=664, obesity, PMID 40555243) all met primary endpoints. Approved by China's NMPA for both T2DM (January 2026) and chronic weight management (March 2026). NOT FDA-approved. Important gaps: evidence base is dominated by manufacturer-sponsored studies conducted exclusively in Chinese populations; no US FDA approval; no cardiovascular outcomes trial; limited postmarketing experience in the source set.
1Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog.NCT04389775PMID 37364710
Guo W et al. - Molecular Metabolism (2023) - Preclinical + Phase 1 clinical trial - In vitro assays; db/db mice; diet-induced-obese rats; Phase 1 SAD 0.03-1.0 mg, MAD 0.2-0.6 mg in healthy volunteers (exact human N not stated in abstract)
Ecnoglutide potently induced cAMP (EC50 = 0.018 nM) but not receptor internalization (EC50 > 10 microM), indicating cAMP-biased signaling (>500,000-fold bias). In rodent models, ecnoglutide showed greater blood glucose reduction and body weight loss vs. semaglutide. Phase 1: safe and well tolerated, half-life 124-138 hours at steady state. Adverse events: decreased appetite, nausea, headache.
Limitations: Phase 1 healthy volunteer data only. Small sample size. Preclinical semaglutide comparisons may not translate to clinical setting. Exact human N not given in abstract. Manufacturer-funded study (Sciwind Biosciences).
2Efficacy and safety of GLP-1 analog ecnoglutide in adults with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial.PMID 39333121
Zhu D et al. - Nature Communications (2024) - Phase 2 RCT - 145 adults with T2DM
Dose-dependent HbA1c reductions: -1.81% (0.4 mg), -1.90% (0.8 mg), -2.39% (1.2 mg) vs. -0.55% placebo (P < 0.0001). 71.9% of 1.2 mg group achieved HbA1c <= 6.5% vs. 9.1% placebo. 33.3% of 1.2 mg group achieved >= 5% body weight loss vs. 3.0% placebo. Specific AE rates: diarrhea 14.7%, nausea 11.9%, constipation 7.3%. Generally safe and well tolerated.
Limitations: 20-week treatment period. Relatively small sample. All participants Chinese. Manufacturer-funded (Sciwind Biosciences). China Drug Trials Registry CTR20211014.
3Efficacy and safety of cAMP signalling-biased GLP-1 analogue ecnoglutide monotherapy versus placebo in patients with type 2 diabetes (EECOH-1): a multi-centre, randomised, double-blind, placebo-controlled, phase 3 trial.NCT05680155PMID 41501026
Zhu D et al. - Nature Communications (2026) - Phase 3 RCT - 211 participants from 32 centres in China
At 24 weeks, HbA1c reductions: -1.96% (0.6 mg, 95% CI -2.18 to -1.73) and -2.43% (1.2 mg, 95% CI -2.65 to -2.20) vs. -0.87% placebo. Treatment difference vs. placebo: -1.09% (0.6 mg, p=0.0003) and -1.56% (1.2 mg, p<0.0001). Body weight changes: -3.04 kg (0.6 mg) and -3.21 kg (1.2 mg) vs. -1.45 kg placebo. HbA1c separation evident by week 4.
Limitations: 24-week treatment period. Chinese population only. Monotherapy -- no active GLP-1 agonist comparator. Randomization 2:2:1:1 -- smaller placebo groups. No cardiovascular or renal outcomes data. Manufacturer-funded (Sciwind Biosciences).
4Efficacy and safety of cAMP-biased GLP-1 receptor agonist ecnoglutide versus dulaglutide in patients with type 2 diabetes and elevated glucose concentrations on metformin monotherapy (EECOH-2): a 52-week, multicentre, open-label, non-inferiority, randomised, phase 3 trial.NCT05680129PMID 40854315
He Y et al. - The Lancet Diabetes & Endocrinology (2025) - Phase 3 RCT (active-controlled, non-inferiority) - 621 participants from 52 hospitals in China
At week 32, HbA1c reductions: -1.91% (ecnoglutide 0.6 mg), -1.89% (1.2 mg) vs. -1.65% (dulaglutide 1.5 mg). Both ecnoglutide doses non-inferior to dulaglutide. 1.2 mg statistically superior (treatment difference -0.24%, p=0.). though authors judged the difference not clinically relevant. Reductions sustained to week 52. Discontinuation due to AEs: 3% (ecnoglutide 0.6 mg), 4% (1.2 mg), 3% (dulaglutide).
Limitations: Open-label design (no blinding for ecnoglutide vs. dulaglutide). Chinese population only. Superiority of 1.2 mg was statistically significant but not considered clinically relevant by authors. No semaglutide comparator. Manufacturer-funded (Sciwind Biosciences).
5Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.NCT05813795PMID 40555243
Ji L et al. - The Lancet Diabetes & Endocrinology (2025) - Phase 3 RCT (SLIMMER trial) - 664 participants from 36 centres in China
At week 40, body weight change: -9.1% (1.2 mg), -10.9% (1.8 mg), -13.2% (2.4 mg) vs. +0.1% placebo (all p<0.0001). Proportion with >= 5% weight loss: 77%, 84%, 87% vs. 16%. At 48 weeks, higher doses continued weight loss without plateau (up to 15.4% at 2.4 mg, with 92.8% achieving clinically meaningful weight loss). Improved waist circumference, BP, lipids, HbA1c, fasting glucose, insulin, uric acid, liver fat, and CRP. TEAEs: 93% vs 84% placebo; 10 discontinuations due to AEs. Most common AEs: mild-to-moderate GI events.
Limitations: Chinese population only (BMI thresholds differ from Western criteria). No active comparator (only placebo). 48-week duration -- longer-term data needed. No cardiovascular outcome data. Manufacturer-funded (Sciwind Biosciences).
6Ecnoglutide, a biased GLP-1 receptor agonist as a potential new player for type 2 diabetes management?PMID 40854316
Scheen AJ - The Lancet Diabetes & Endocrinology (2025) - Editorial/Commentary - N/A
Expert commentary discussing ecnoglutide's cAMP signaling bias as a novel pharmacological approach. Raises key question: does biased agonism confer clinically meaningful advantage? Notes need for head-to-head comparison with pharmacokinetically matched balanced GLP-1 analog.
Limitations: Commentary, not primary research. No abstract available.
7A Promising Path Forward in Obesity Pharmacotherapy: Ecnoglutide and the Evolution of GLP-1R Agonist Design
Zhou L et al. - BIO Integration (2025) - Editorial/Commentary - N/A
Reviews ecnoglutide SLIMMER results in context of GLP-1 agonist evolution. Notes 48-week weight loss of 9.9%, 13.3%, and 15.4% (1.2, 1.8, 2.4 mg). Discusses structural basis of biased agonism. Raises question whether biased agonism is clinically superior to balanced agonism.
Limitations: Commentary, not primary research.
8A Study to Compare XW003 Injection and Semaglutide Injection in Chinese Adults With Obesity (SLIMMER-UP-SWITCH)NCT07073417
Sciwind Biosciences - ClinicalTrials.gov (2025) - Phase 2 RCT (head-to-head vs semaglutide) - Recruiting
Active trial comparing ecnoglutide injection vs. semaglutide injection in Chinese adults with obesity. First head-to-head comparison with semaglutide.
Limitations: Not yet completed. Results not available.
9A Study of Weekly Oral Ecnoglutide (VRB-101) in Participants Who Have Obesity or Overweight With Weight-Related ComorbiditiesNCT07281937
Verdiva Bio / Sciwind Biosciences - ClinicalTrials.gov (2025) - Phase 2 RCT (oral formulation) - Recruiting
Phase 2 trial evaluating oral ecnoglutide (VRB-101) once weekly in overweight/obesity. Represents oral formulation advancement for global markets.
Limitations: Not yet completed. Oral formulation pharmacokinetics and bioavailability not yet publicly reported.
10A Phase Ib/IIa Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral Ecnoglutide Tablets in Chinese Participants With Overweight or ObesityNCT07243171
Sciwind Biosciences - ClinicalTrials.gov (2025) - Phase 1b/2a - Recruiting
Early-phase evaluation of oral ecnoglutide tablet formulation safety, tolerability, PK, and PD in overweight/obese Chinese participants.
Limitations: Not yet completed. Early-stage oral formulation data.
11XW004 To Evaluate the Safety, Tolerability, PK, and PD of Oral Ecnoglutide Tablet in Healthy AdultsNCT05184322
Sciwind Biosciences - ClinicalTrials.gov (2022) - Phase 1 - Completed
First-in-human study of oral ecnoglutide tablet formulation. Completed but results not published.
Limitations: Results not publicly disclosed.
12A Drug-Drug Interaction Study Between XW003 and Metformin, Warfarin, Rosuvastatin or DigoxinNCT06335134
Sciwind Biosciences - ClinicalTrials.gov (2024) - Phase 1 (DDI study) - Completed
Drug-drug interaction study evaluating ecnoglutide interactions with metformin, warfarin, rosuvastatin, and digoxin. Completed but results not published.
Limitations: Results not publicly disclosed.
13Ecnoglutide in Adolescents With ObesityNCT07143227
Sciwind Biosciences - ClinicalTrials.gov (2025) - Phase 3 (adolescent obesity) - Recruiting
Expanding ecnoglutide clinical program to adolescent obesity population.
Limitations: Not yet completed.
14Ecnoglutide in Obesity With Obstructive Sleep ApneaNCT07387094
Sciwind Biosciences - ClinicalTrials.gov (2025) - Phase 3 (obesity + OSA) - Recruiting
Evaluating ecnoglutide in adults with obesity and obstructive sleep apnea.
Limitations: Not yet completed.
15Ecnoglutide in Obesity With Obstructive Sleep Apnea (2)NCT07434050
Sciwind Biosciences - ClinicalTrials.gov (2025) - Phase 3 (obesity + OSA) - Recruiting
Second trial evaluating ecnoglutide in obesity with obstructive sleep apnea.
Limitations: Not yet completed.
16Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review.PMID 38343381
Espinosa De Ycaza AE et al. - Thyroid (2024) - Narrative review - N/A
Biological plausibility for GLP-1 RA and medullary thyroid cancer in rodents, less clear for non-MTC in humans. No conclusive evidence of elevated thyroid cancer risk from clinical trial and observational data.
Limitations: Review, not primary research. Does not specifically evaluate ecnoglutide. GLP-1 class-level evidence.
17Emerging pharmacotherapies for obesity: A systematic review.PMID 39952695
Kokkorakis M et al. - Pharmacological Reviews (2025) - Systematic review - 53 Phase 2/3 trials, 36 drugs
Identified ecnoglutide as one of 14 drugs with ongoing Phase 3 trials. Classified among GLP-1 RAs alongside orforglipron and TG103.
Limitations: Broad systematic review, not ecnoglutide-specific. Searched 2012-2024, does not include 2025-2026 Phase 3 publications.