The Role of CYP8B1 Polymorphisms in Modulating the Biochemical Pathways Affected by SGLT2 Inhibitors in T2DM and Obesity

NCT07120828 | Completed Phase 4

• 2 other identifiers: EPU-CYP8B1-SGLT2-T2DM-2025-01No: 2348524, February 21, 2025
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

Brief Summary

This study explores the long-term effects of dapagliflozin and empagliflozin on CYP8B1 gene expression and a range of metabolic, oxidative, and inflammatory biomarkers in obese patients with Type 2 Diabetes Mellitus (T2DM). Over a 6-month period, participants are assigned to three treatment arms: metformin (control), dapagliflozin, and empagliflozin. The study aims to determine how these medications influence bile acid metabolism, oxidative stress, leptin, GLP-1, IL-10, and IFN-γ, providing insight into the broader metabolic benefits of SGLT2 inhibitors

Conditions

Type 2 Diabetes; Obese Diabetics; Obese Patients (BMI ≥ 30 kg/m²)

Keywords

CYP8B1; Obese diabetics; oxidative stress

Outcome Measures

Primary Outcomes (4)

• Change in Body Weight (kg) from Baseline to 6 Months

  Body weight will be measured using a calibrated digital scale at baseline and at 6 months. The change in weight will be calculated by subtracting baseline weight from 6-month weight.

  Baseline and 6 months

• Change in Serum Total Cholesterol (mg/dL) from Baseline to 6 Months

  Serum total cholesterol will be measured using standard enzymatic methods at baseline and after 6 months. The change will be calculated by subtracting baseline values from follow-up values.

  Baseline to 6 Months

• Change in Malondialdehyde (MDA) Levels (µmol/L) from Baseline to 6 Months

  Serum MDA will be measured using the TBARS assay to assess lipid peroxidation and oxidative stress.

  Baseline to 6 Months

• CYP8B1 Gene Expression Changes

  Measure CYP8B1 mRNA expression using real-time PCR to evaluate the relationship between gene expression and treatment response.

  Baseline to 6 Months

Secondary Outcomes (14)

• Change in Adiponectin Levels

  Baseline to 6 Months

• Change in HbA1c

  Baseline to 6 Months

• Change in Fasting Blood Glucose

  Baseline to 6 Months

• Change in C-Peptide Levels

  Baseline to 6 Months

• Change in Blood Ketone Body Levels

  Baseline to 6 Months

Study Arms (3)

Empagliflozin Group

EXPERIMENTAL

Participants in this group will receive empagliflozin 10 mg orally once daily for a duration of 6 months. The intervention aims to evaluate the effect of empagliflozin on weight reduction, metabolic parameters, and biochemical outcomes in newly diagnosed obese T2DM patients, with a focus on the influence of CYP8B1 polymorphisms on treatment response.

Drug: Empagliflozin (oral)

Dapagliflozin Group

EXPERIMENTAL

Participants in this group will receive dapagliflozin 10 mg orally once daily for a duration of 6 months. This arm is designed to assess the clinical and biochemical effects of dapagliflozin, particularly regarding changes in adipokines, lipid profile, insulin sensitivity, and the impact of CYP8B1 genetic variations.

Drug: Dapagliflozin (DAPA)

Control Group

ACTIVE COMPARATOR

Participants in this group will receive standard care, including dietary and lifestyle modifications and metformin therapy if clinically indicated, according to ADA guidelines. This arm will serve as a comparator to evaluate the relative efficacy of SGLT2 inhibitors and the role of CYP8B1 polymorphisms in treatment outcomes.

Drug: Metfomin

Interventions

Empagliflozin (oral) DRUG

Empagliflozin 10 mg oral tablet administered once daily for 6 months.

Empagliflozin Group

Metfomin DRUG

metformin 500-1000 mg/day administered as part of standard care, based on clinical indication.

Control Group

Dapagliflozin (DAPA) DRUG

Dapagliflozin 10 mg oral tablet administered once daily for 6 months

Dapagliflozin Group

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed with Type 2 Diabetes Mellitus (within the past 6 months).
• Body Mass Index (BMI) ≥ 30 kg/m² (classified as obese).
• No prior treatment with SGLT2 inhibitors or other antidiabetic medications.
• Willing and able to provide written informed consent.
• Able to comply with study visits, procedures, and sample collection.

You may not qualify if:

• History or diagnosis of Type 1 diabetes mellitus or secondary forms of diabetes.
• Estimated Glomerular Filtration Rate (eGFR) \< 45 mL/min/1.73 m² (moderate to severe renal impairment).
• Active liver disease or significant hepatic dysfunction.
• Current pregnancy or breastfeeding.
• Known hypersensitivity or contraindication to SGLT2 inhibitors.
• hypertension
• Any other condition that, in the opinion of the investigator, may interfere with the patient's ability to complete the study or pose additional risk.

Sponsors & Collaborators

• Erbil Polytechnic University: lead
• Kurdistan Higher Council of Medical Specialties: collaborator

Study Sites (1)

Epu

Erbil, Kurdistan, 44001, Iraq

Location

Related Publications (8)

• Scheen AJ. Sodium-glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2020 Oct;16(10):556-577. doi: 10.1038/s41574-020-0392-2. Epub 2020 Aug 27.

  PMID: 32855502 RESULT

• Malone JI, Hansen BC. Does obesity cause type 2 diabetes mellitus (T2DM)? Or is it the opposite? Pediatr Diabetes. 2019 Feb;20(1):5-9. doi: 10.1111/pedi.12787. Epub 2018 Nov 5.

  PMID: 30311716 RESULT

• Klen J, Dolzan V. Treatment Response to SGLT2 Inhibitors: From Clinical Characteristics to Genetic Variations. Int J Mol Sci. 2021 Sep 10;22(18):9800. doi: 10.3390/ijms22189800.

  PMID: 34575958 RESULT

• Hegyi P, Maleth J, Walters JR, Hofmann AF, Keely SJ. Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease. Physiol Rev. 2018 Oct 1;98(4):1983-2023. doi: 10.1152/physrev.00054.2017.

  PMID: 30067158 RESULT

• Fioretto P, Zambon A, Rossato M, Busetto L, Vettor R. SGLT2 Inhibitors and the Diabetic Kidney. Diabetes Care. 2016 Aug;39 Suppl 2:S165-71. doi: 10.2337/dcS15-3006.

  PMID: 27440829 RESULT

• Chiang JYL, Ferrell JM. Bile Acids as Metabolic Regulators and Nutrient Sensors. Annu Rev Nutr. 2019 Aug 21;39:175-200. doi: 10.1146/annurev-nutr-082018-124344. Epub 2019 Apr 24.

  PMID: 31018107 RESULT

• Chiang JY. Bile acid metabolism and signaling. Compr Physiol. 2013 Jul;3(3):1191-212. doi: 10.1002/cphy.c120023.

  PMID: 23897684 RESULT

• Sarafidis PA, Tsapas A. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2016 Mar 17;374(11):1092. doi: 10.1056/NEJMc1600827. No abstract available.

  PMID: 26981941 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin; dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD Student (under supervision of Prof. goran othman )

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: August 13, 2025
• Study Start: July 15, 2025
• Primary Completion: August 30, 2025
• Study Completion: March 15, 2026
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)