SGLT-2 Inhibition, Metabolomics and Cardiovascular/Kidney Disease

NCT ID: NCT03919656

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-12
• Study Completion Date: 2024-05-23

Brief Summary

This study evaluates the metabolomics changes associated with dapagliflozin treatment in patients with type 2 diabetes mellitus (T2DM). The participants in the study will be randomized to receive 10 mg dapagliflozin or placebo once daily for 12 weeks.

Detailed Description

In this study, we hypothesize that metabolomics changes that occur in patients with T2DM after initiating SGLT2i (sodium-glucose cotransporter 2 inhibitors) treatment may be responsible for the beneficial cardiovascular and kidney effects observed in clinical trials with SGLT2i. Also, we propose that the study of the specific metabolome associated with the treatment with SGLT2i could help identify the possible metabolites and molecules that reduce CVD (cardiovascular disease) and renal disease in patients with T2DM.

The participants in the study will be randomized to receive 10 mg dapagliflozin or placebo once daily of for 12 weeks. Besides, all participants will be advised to engage in 150 min or more of moderate-to vigorous intensity physical activity per week, spread over at least 3 days/week, with no more than 2 consecutive days without activity and to engage in 2-3 sessions/week of resistance exercise on nonconsecutive days. Moreover, these patients will be advised to follow a lifestyle program that achieve a 500-750 kcal/day energy deficit or provide≈1,200-1,500 kcal/day for women and 1,500-1,800 kcal/day for men, adjusted for the individual's baseline body weight.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Dapagliflozin

Dapagliflozin 10 mg daily (orally)

Group Type: EXPERIMENTAL

Dapagliflozin 10 mg

Intervention Type: DRUG

Dapagliflozin 10 mg daily in a green, plain, diamond shaped, film coated tablet (orally)

Placebo

Matching placebo for dapagliflozin daily (orally). Does not contain active ingredient

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Green, plain, diamond shaped, film coated tablet (orally). Does not contain active ingredient

Interventions

Dapagliflozin 10 mg

Dapagliflozin 10 mg daily in a green, plain, diamond shaped, film coated tablet (orally)

Intervention Type: DRUG

Placebo Oral Tablet

Green, plain, diamond shaped, film coated tablet (orally). Does not contain active ingredient

Intervention Type: DRUG

Other Intervention Names

Farxiga 10 mg

Eligibility Criteria

Inclusion Criteria

• Age 18-75.
• BMI 27-39.9 kg/m2.
• T2DM on treatment with metformin and inadequate metabolic control (defined as HbA1c≥6.5 -7%).

Exclusion Criteria

• Pregnancy (all women of child-bearing age, unless on treatment with contraceptive methods, will undergo a pregnancy test)
• Breastfeeding
• Intolerance/allergy to dapagliflozin.
• Treatment with antidiabetic drug other than metformin.
• Impaired kidney function: Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 (calculated using the CKD-EPI formula).
• Patients with established cardiovascular disease.
• Previous or current history of cancer of any kind.
• Uncontrolled hypertension (systolic blood pressure≥160 mmHg or diastolic blood pressure≥110 mmHg, despite adequate antihypertensive treatment).
• History of liver tumour or acute or chronic liver disease with impaired liver function: total bilirubin levels> 2.0 mg / dl or GOT/GPT levels three times higher than normal upper limit.
• Known HIV infection or active HBV or HCV infection.
• Other serious underlying diseases, which could affect the patient's ability to participate in the study.
• Reduced life expectancy (<12 months) due to advanced or terminal concomitant diseases.

In addition, female patients of child-bearing age will be advised to use contraceptive methods during the study period, given the contraindication of dapagliflozin and metformin during pregnancy as per normal clinical practice.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jose Carlos Fernandez-Garcia, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Virgen de la Victoria Hospital

Locations

Virgen de la Victoria University Hospital. Endocrinology Department

Málaga, Spain, Spain

Countries

Spain

Other Identifiers

FIM-DAPA-2018-01

Identifier Type: -

Identifier Source: org_study_id