NCT07558863

Brief Summary

This study aims to investigate whether a class of diabetes medications called GLP-1 receptor agonists (GLP-1RA), specifically semaglutide or polyethylene glycol loxenatide, can improve heart-related nerve damage in people with type 2 diabetes. This heart-related nerve damage is known as diabetic cardiac autonomic neuropathy (DCAN), which can cause problems such as fast resting heart rate, low blood pressure upon standing, and in severe cases, heart attack or sudden death. In this study, 60 adults with type 2 diabetes (ages 18-80) will be randomly divided into two groups. One group will receive standard diabetes care only, while the other group will receive standard care plus a once-weekly injection of either semaglutide or polyethylene glycol loxenatide for 6 months. Participants will undergo tests before and after the treatment period, including blood tests and non-invasive heart function tests (24-hour heart rate variability monitoring and cardiac autonomic reflex tests). The main goal is to see whether GLP-1RA treatment improves heart rate variability, a key sign of heart nerve function. The study also looks at changes in body weight, blood sugar control, and insulin resistance. This research may help determine whether GLP-1RA medications can protect against or improve diabetic heart nerve damage, beyond their known benefits for blood sugar control.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for phase_4 type-2-diabetes

Timeline
28mo left

Started Apr 2026

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress4%
Apr 2026Aug 2028

Study Start

First participant enrolled

April 1, 2026

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

April 14, 2026

Completed
16 days until next milestone

First Posted

Study publicly available on registry

April 30, 2026

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 30, 2028

Expected
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 30, 2028

Last Updated

April 30, 2026

Status Verified

April 1, 2026

Enrollment Period

2 years

First QC Date

April 14, 2026

Last Update Submit

April 27, 2026

Conditions

Type 2 DiabetesDiabetes With Diabetic Autonomic Neuropathy (Diagnosis)

Keywords

T2DMDCANHRVCART

Outcome Measures

Primary Outcomes (1)

  • heart rate variability（HRV）

    All participants were given ambulatory electrocardiogram.The time domain analysis and frequency domain analysis of heart rate variability are included in the holter ECG report.

    baseline and 12 weeks later]

Secondary Outcomes (5)

  • E/I difference

    basline and 12 weeks later

  • 30/15 ratio

    basline and 12 weeks later

  • Valsalva action

    basline and 12 weeks later

  • the difference between lying and Orthostatic blood pressure

    basline and 12 weeks later

  • grip strength tests

    basline and 12 weeks later

Study Arms (2)

Control Group

NO INTERVENTION

Participants receive standard diabetes care (routine glucose-lowering treatment) without GLP-1 receptor agonist (GLP-1RA) intervention.

GLP-1 Receptor Agonist (GLP-1RA) Group

EXPERIMENTAL

Participants receive standard diabetes care plus a once-weekly subcutaneous injection of a GLP-1 receptor agonist (either semaglutide or polyethylene glycol loxenatide) for 6 months. Semaglutide is administered at 0.5 mg once weekly; polyethylene glycol loxenatide is administered at 0.2 mg once weekly. Both are used within approved labeling for type 2 diabetes.

Drug: GLP-1 Receptor Agonists

Interventions

GLP-1 Receptor AgonistsDRUG

GLP-1 receptor agonists are administered as a once-weekly subcutaneous injection for 6 months. Two specific GLP-1RAs are used in this study: semaglutide at 0.5 mg once weekly, or polyethylene glycol loxenatide at 0.2 mg once weekly. Both are approved for the treatment of type 2 diabetes and are used within their approved dosing guidelines.

GLP-1 Receptor Agonist (GLP-1RA) Group

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients aged 18-70 years
  • Patients with type 2 diabetes mellitus (T2DM) who meet the diagnostic guidelines
  • Patient has signed the relevant informed consent form
  • Being overweight or obese (BMI ≥ 24 kg/m²)

You may not qualify if:

  • Age \< 18 years
  • Pregnant or lactating women
  • Acute or chronic pancreatitis
  • Recent acute complications of diabetes (e.g., diabetic ketoacidosis, hyperosmolar hyperglycemic state)
  • Arrhythmia or taking medications that affect heart rate (e.g., beta-blockers, non-dihydropyridine calcium channel blockers, antiarrhythmic drugs)
  • Thyroid disease
  • Severe organ dysfunction (e.g., heart, liver, kidney failure)
  • Denial of informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

the First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

Related Publications (15)

  • Takaku S, Tsukamoto M, Niimi N, Yako H, Sango K. Exendin-4 Promotes Schwann Cell Survival/Migration and Myelination In Vitro. Int J Mol Sci. 2021 Mar 15;22(6):2971. doi: 10.3390/ijms22062971.

    PMID: 33804063RESULT

  • Mehta K, Behl T, Kumar A, Uddin MS, Zengin G, Arora S. Deciphering the Neuroprotective Role of Glucagon-like Peptide-1 Agonists in Diabetic Neuropathy: Current Perspective and Future Directions. Curr Protein Pept Sci. 2021;22(1):4-18. doi: 10.2174/1389203721999201208195901.

    PMID: 33292149RESULT

  • Lee HS, Han J, Lee SH, Park JA, Kim KW. Meteorin promotes the formation of GFAP-positive glia via activation of the Jak-STAT3 pathway. J Cell Sci. 2010 Jun 1;123(Pt 11):1959-68. doi: 10.1242/jcs.063784. Epub 2010 May 11.

    PMID: 20460434RESULT

  • Jorgensen JR, Thompson L, Fjord-Larsen L, Krabbe C, Torp M, Kalkkinen N, Hansen C, Wahlberg L. Characterization of Meteorin--an evolutionary conserved neurotrophic factor. J Mol Neurosci. 2009 Sep;39(1-2):104-16. doi: 10.1007/s12031-009-9189-4. Epub 2009 Mar 4.

    PMID: 19259827RESULT

  • Kikel-Coury NL, Brandt JP, Correia IA, O'Dea MR, DeSantis DF, Sterling F, Vaughan K, Ozcebe G, Zorlutuna P, Smith CJ. Identification of astroglia-like cardiac nexus glia that are critical regulators of cardiac development and function. PLoS Biol. 2021 Nov 18;19(11):e3001444. doi: 10.1371/journal.pbio.3001444. eCollection 2021 Nov.

    PMID: 34793438RESULT

  • Aksu T, Gupta D, Pauza DH. Anatomy and Physiology of Intrinsic Cardiac Autonomic Nervous System: Da Vinci Anatomy Card #2. JACC Case Rep. 2021 Apr 21;3(4):625-629. doi: 10.1016/j.jaccas.2021.02.018. eCollection 2021 Apr.

    PMID: 34317590RESULT

  • Kapa S, DeSimone CV, Asirvatham SJ. Innervation of the heart: An invisible grid within a black box. Trends Cardiovasc Med. 2016 Apr;26(3):245-57. doi: 10.1016/j.tcm.2015.07.001. Epub 2015 Jul 9.

    PMID: 26254961RESULT

  • Wink J, van Delft R, Notenboom RGE, Wouters PF, DeRuiter MC, Plevier JWM, Jongbloed MRM. Human adult cardiac autonomic innervation: Controversies in anatomical knowledge and relevance for cardiac neuromodulation. Auton Neurosci. 2020 Sep;227:102674. doi: 10.1016/j.autneu.2020.102674. Epub 2020 May 16.

    PMID: 32497872RESULT

  • Dimitropoulos G, Tahrani AA, Stevens MJ. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes. 2014 Feb 15;5(1):17-39. doi: 10.4239/wjd.v5.i1.17.

    PMID: 24567799RESULT

  • Williams SM, Eleftheriadou A, Alam U, Cuthbertson DJ, Wilding JPH. Cardiac Autonomic Neuropathy in Obesity, the Metabolic Syndrome and Prediabetes: A Narrative Review. Diabetes Ther. 2019 Dec;10(6):1995-2021. doi: 10.1007/s13300-019-00693-0. Epub 2019 Sep 24.

    PMID: 31552598RESULT

  • Kaze AD, Yuyun MF, Fonarow GC, Echouffo-Tcheugui JB. Cardiac autonomic dysfunction and risk of incident stroke among adults with type 2 diabetes. Eur Stroke J. 2023 Mar;8(1):275-282. doi: 10.1177/23969873221127108. Epub 2022 Nov 1.

    PMID: 37021204RESULT

  • Goh JK, Koh L. Evaluating treatment options for cardiovascular autonomic neuropathy in patients with diabetes mellitus: a systematic review. Diabetol Int. 2023 Apr 25;14(3):224-242. doi: 10.1007/s13340-023-00629-x. eCollection 2023 Jul.

    PMID: 37397902RESULT

  • Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003 May;26(5):1553-79. doi: 10.2337/diacare.26.5.1553.

    PMID: 12716821RESULT

  • Balcioglu AS, Muderrisoglu H. Diabetes and cardiac autonomic neuropathy: Clinical manifestations, cardiovascular consequences, diagnosis and treatment. World J Diabetes. 2015 Feb 15;6(1):80-91. doi: 10.4239/wjd.v6.i1.80.

    PMID: 25685280RESULT

  • Maser RE, Lenhard MJ. Cardiovascular autonomic neuropathy due to diabetes mellitus: clinical manifestations, consequences, and treatment. J Clin Endocrinol Metab. 2005 Oct;90(10):5896-903. doi: 10.1210/jc.2005-0754. Epub 2005 Jul 12.

    PMID: 16014401RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Disease

Interventions

Glucagon-Like Peptide-1 Receptor Agonists

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hypoglycemic AgentsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and Uses

Central Study Contacts

jianbo Li

CONTACT

13115008178ljbzjlx18@aliyun.com

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 14, 2026

First Posted

April 30, 2026

Study Start

April 1, 2026

Primary Completion (Estimated)

March 30, 2028

Study Completion (Estimated)

August 30, 2028

Last Updated

April 30, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)