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Type 2 Diabetes Mellitus (T2DM)NRG4-T2DMNCT07734558

Evaluation of Neuregulin-4 (NRG4) Levels in Obese and Non-Obese Patients With Type 2 Diabetes Mellitus

An observational study of Type 2 Diabetes Mellitus (T2DM) and Obesity Type 2 Diabetes Mellitus, run by GÜLDEN ANATACA at 1 site in Turkey (Türkiye).

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

This prospective observational study aims to evaluate serum Neuregulin-4 (NRG4) concentrations in obese and non-obese adults with Type 2 Diabetes Mellitus (T2DM) and to investigate their association with obesity status, insulin resistance, and different antidiabetic treatment regimens. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
How many people
125 participants
Where
1 siteTurkey (Türkiye)
Study dates
Jun 2026to 30 Dec 2026
How long will I take part?
1 Day
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: The study population will consist of obese and non-obese adult participants aged 18-65 years who are admitted to the outpatient clinic. The study will include newly diagnosed treatment-naive Type 2 Diabetes Mellitus patients, patients with at least 6 months of Type 2 DM diagnosis receiving different antidiabetic treatment combinations, and healthy control participants without diabetes mellitus.

Who may be able to join

  • Age 18-65 years
  • Newly diagnosed treatment-naïve T2DM
  • T2DM treated for at least 6 months
  • BMI >30 kg/m²
  • BMI <25 kg/m²
  • No pregnancy
Show all 10Show fewer
  • No breastfeeding
  • No active infection
  • No inflammatory disease
  • Written informed consent

Who cannot join

  • Age <18 years
  • Pregnancy
  • Breastfeeding
  • Active infection
  • Rheumatologic disease
  • Refusal to participate

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

GÜLDEN ANATACA contact

+905059284244

ganataca@yahoo.com

Turkey (Türkiye)1 site
  • Kanuni Sultan Süleyman Training and Research Hospital

    Istanbul

    gülden ANATACA, +905059284244, ganataca@yahoo.com

Other trials in Turkey (Türkiye)

About this study

Official title: Evaluation of the Relationship Between Serum Neuregulin-4 (NRG4) Levels, Obesity Status, and Antidiabetic Treatment Regimens in Patients With Type 2 Diabetes Mellitus: A Prospective Observational Study

This prospective observational study aims to evaluate serum Neuregulin-4 (NRG4) concentrations in obese and non-obese adults with Type 2 Diabetes Mellitus (T2DM) and to investigate their association with obesity status, insulin resistance, and different antidiabetic treatment regimens. Participants will be categorized into five predefined groups according to obesity status and treatment regimen, including SGLT2 inhibitor users, non-SGLT2 oral antidiabetic therapy users, SGLT2 combination therapy users, newly diagnosed treatment-naïve patients, and healthy controls. Clinical, anthropometric, and laboratory parameters including fasting plasma glucose, HbA1c, estimated glomerular filtration rate (eGFR), body mass index, waist circumference, waist-to-hip ratio, and serum NRG4 concentrations will be evaluated. The study aims to determine whether NRG4 may serve as a novel biomarker reflecting metabolic status and treatment response in patients with T2DM.

Read the detailed description

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, resulting in persistent hyperglycemia and an increased risk of both microvascular and macrovascular complications. Obesity is one of the strongest risk factors for the development and progression of T2DM and is associated with chronic low-grade inflammation, dysregulated adipokine secretion, and impaired glucose and lipid metabolism. Despite advances in antidiabetic therapies, identifying novel biomarkers that reflect metabolic status and treatment response remains an important research priority.

Neuregulin-4 (NRG4) is a recently identified adipokine predominantly secreted by brown adipose tissue. Experimental and clinical studies have demonstrated that NRG4 plays an important role in maintaining metabolic homeostasis by regulating glucose metabolism, improving insulin sensitivity, suppressing hepatic lipogenesis, and reducing systemic inflammation. Reduced circulating NRG4 concentrations have been associated with obesity, insulin resistance, non-alcoholic fatty liver disease, metabolic syndrome, and Type 2 Diabetes Mellitus. Lower serum NRG4 levels may therefore represent a potential biomarker of metabolic dysfunction and disease severity.

Although previous studies have investigated the association between serum NRG4 concentrations and obesity or T2DM separately, limited evidence is available regarding the relationship between NRG4 levels, obesity status, and different antidiabetic treatment regimens within the same patient population. In particular, the potential influence of sodium-glucose cotransporter-2 (SGLT2) inhibitors and other commonly used antidiabetic therapies on circulating NRG4 concentrations has not been adequately investigated.

This single-center, prospective observational study aims to evaluate serum NRG4 concentrations in obese and non-obese adults with Type 2 Diabetes Mellitus and to investigate their relationship with different antidiabetic treatment regimens. Participants will be consecutively recruited from the outpatient clinic and classified into five predefined groups according to diabetes status and current treatment regimen: (1) patients receiving SGLT2 inhibitor monotherapy; (2) patients receiving oral antidiabetic therapy without SGLT2 inhibitors; (3) patients receiving combination therapy including SGLT2 inhibitors; (4) newly diagnosed treatment-naïve patients with T2DM; and (5) healthy individuals without diabetes who will serve as the control group.

Clinical and demographic characteristics including age, sex, body mass index (BMI), waist circumference, waist-to-hip ratio, smoking status, and current antidiabetic medications will be recorded. Routine biochemical parameters, including fasting plasma glucose, glycated hemoglobin (HbA1c), and estimated glomerular filtration rate (eGFR), will be obtained from routine clinical evaluations. In addition, one peripheral venous blood sample will be collected from each participant for serum NRG4 measurement. Blood samples will be centrifuged, serum aliquots will be stored at -80°C, and serum NRG4 concentrations will be measured using a validated enzyme-linked immunosorbent assay (ELISA).

The primary outcome of the study is the comparison of serum NRG4 concentrations among the predefined study groups. Secondary analyses will evaluate the associations between serum NRG4 concentrations and obesity-related anthropometric measurements, glycemic control, renal function, and different antidiabetic treatment modalities.

The findings of this study are expected to improve the understanding of the role of NRG4 in the pathophysiology of obesity and Type 2 Diabetes Mellitus and may provide evidence supporting the clinical utility of NRG4 as a novel biomarker for metabolic status and treatment response. The results may also contribute to the identification of future therapeutic targets for patients with obesity and T2DM.

Keywords
Neuregulin-4, NRG4, Type 2 Diabetes Mellitus, Obesity, Adipokine
Medical subject headings
Diabetes Mellitus, Type 2, Insulin Resistance, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT07734558
Study groupRoleWhat they receive
SGLT2 GroupType 2 Diabetes Mellitus patients receiving only SGLT2 inhibitor treatment will be included in this group. Serum NRG4 levels and metabolic parameters will be evaluated.
Non-SGLT2 OAD GroupType 2 Diabetes Mellitus patients receiving metformin with or without insulin therapy, but not receiving SGLT2 inhibitors, will be included in this group.
SGLT2 Combination GroupType 2 Diabetes Mellitus patients receiving metformin with or without insulin together with SGLT2 inhibitor therapy will be included in this group.
Newly Diagnosed DM GroupNewly diagnosed treatment-naive Type 2 Diabetes Mellitus patients who have not received any antidiabetic therapy will be included in this group.
Healthy Control GroupAge-matched participants without Diabetes Mellitus diagnosis will be included as healthy controls for comparison of serum NRG4 levels and metabolic parameters.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Serum Neuregulin-4 (NRG4) Levels in Obese and Non-Obese Type 2 Diabetic Patients

    The primary outcome of this study is the evaluation and comparison of serum Neuregulin-4 (NRG4) levels among obese and non-obese patients with Type 2 Diabetes Mellitus receiving different antidiabetic treatment modalities, as well as healthy control subjects.

    Measured: Baseline (Day 0)

Secondary outcomes (4)
  1. Glycated Hemoglobin (HbA1c)

    HbA1c (%) will be measured to evaluate long-term glycemic control and compared among all study groups.

    Measured: Baseline (Day 0)

  2. Fasting Plasma Glucose

    Fasting plasma glucose (mg/dL) will be measured and compared among the study groups.

    Measured: Baseline (Day 0)

  3. Estimated Glomerular Filtration Rate (eGFR)

    Estimated glomerular filtration rate (mL/min/1.73 m²) will be evaluated to assess renal function and compared among the study groups.

    Measured: Baseline (Day 0)

  4. Body Mass Index (BMI)

    Body mass index (kg/m²) will be calculated using body weight and height and compared between obese and non-obese participants.

    Measured: Baseline (Day 0)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2026
  2. Study startJun 2026 (estimated)
  3. Primary completion30 Aug 2026 (estimated)
  4. Study completion30 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
125 participants (estimated)
Target duration
1 Day
IDs, dates and publications
ClinicalTrials.gov ID
NCT07734558
Sponsor's protocol ID
KAEK/2026.04.1 l8
Acronym
NRG4-T2DM
Status last verified
Jul 2026
First submitted
16 Jul 2026
Last updated
29 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: ndividual participant data (IPD) will not be shared in order to protect participant confidentiality and privacy. The study will report only aggregated and anonymized data in scientific publications and presentations.

Publications

  • Tutunchi H, Mobasseri M, Aghamohammadzadeh N, Hooshyar J, Naeini F, Najafipour F. Serum neuregulin 4 (NRG-4) level and non-alcoholic fatty liver disease (NAFLD): A case-control study. Int J Clin Pract. 2021 Oct;75(10):e14555. doi: 10.1111/ijcp.14555. Epub 2021 Jun 29.

    PubMed 34159710
  • Cai C, Lin M, Xu Y, Li X, Yang S, Zhang H. Association of circulating neuregulin 4 with metabolic syndrome in obese adults: a cross-sectional study. BMC Med. 2016 Oct 24;14(1):165. doi: 10.1186/s12916-016-0703-6.

    PubMed 27772531
  • Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, Chen Z, Cozacov Z, Zhou D, Okunade AL, Su X, Li S, Bluher M, Lin JD. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med. 2014 Dec;20(12):1436-1443. doi: 10.1038/nm.3713. Epub 2014 Nov 17.

    PubMed 25401691
  • Yan P, Xu Y, Wan Q, Feng J, Li H, Yang J, Zhong H, Zhang Z. Plasma Neuregulin 4 Levels Are Associated with Metabolic Syndrome in Patients Newly Diagnosed with Type 2 Diabetes Mellitus. Dis Markers. 2018 Mar 12;2018:6974191. doi: 10.1155/2018/6974191. eCollection 2018.

    PubMed 29721105
  • Kurek Eken M, Sahin Ersoy G, Yayla Abide C, Sanverdi I, Devranoglu B, Kutlu T, Cevik O. Association between circulating neuregulin 4 levels and metabolic, aterogenic, and AMH profile of polycystic ovary syndrome. J Obstet Gynaecol. 2019 Oct;39(7):975-980. doi: 10.1080/01443615.2019.1581754. Epub 2019 May 7.

    PubMed 31064233
  • Villarroya F, Cereijo R, Villarroya J, Giralt M. Brown adipose tissue as a secretory organ. Nat Rev Endocrinol. 2017 Jan;13(1):26-35. doi: 10.1038/nrendo.2016.136. Epub 2016 Sep 12.

    PubMed 27616452
  • Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders. Front Endocrinol (Lausanne). 2016 Apr 13;7:30. doi: 10.3389/fendo.2016.00030. eCollection 2016.

    PubMed 27148161

Questions about this trial

What is this clinical trial studying?

An observational study of Type 2 Diabetes Mellitus (T2DM) and Obesity Type 2 Diabetes Mellitus, run by GÜLDEN ANATACA at 1 site in Turkey (Türkiye).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact GÜLDEN ANATACA (+905059284244, ganataca@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Serum Neuregulin-4 (NRG4) Levels in Obese and Non-Obese Type 2 Diabetic Patients (time frame: Baseline (Day 0)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07734558, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2026.

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