SGLT-2 Inhibition, Metabolomics and Cardiovascular/Kidney Disease

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

Status and phase: Completed; Phase 4

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo Oral Tablet; Drug: Dapagliflozin 10 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT03919656

FIM-DAPA-2018-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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60 participants in 2 patient groups, including a placebo group

Dapagliflozin

Experimental group

Description:

Dapagliflozin 10 mg daily (orally)

Treatment:

Drug: Dapagliflozin 10 mg

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo Oral Tablet