SGLT-2 Inhibition and Cardiovascular Disease. Metabolomics Study of Potential Factors Involved in Cardio- and Nephroprotection
Overview
- Phase
- Phase 4
- Intervention
- Dapagliflozin 10 mg
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Metabolomics changes in blood
- Status
- Completed
- Last Updated
- 10 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •BMI 27-39.9 kg/m
- •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.
Arms & Interventions
Dapagliflozin
Dapagliflozin 10 mg daily (orally)
Intervention: Dapagliflozin 10 mg
Placebo
Matching placebo for dapagliflozin daily (orally). Does not contain active ingredient
Intervention: Placebo Oral Tablet
Outcomes
Primary Outcomes
Metabolomics changes in blood
Time Frame: From baseline to week 12
Targeted and quantitative analysis by ultra-high-resolution liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ/MS). Analysis of specific families of metabolites selected from hypotheses generated by previous exploratory studies: changes in acylcarnitines and other intermediates of mitochondrial β-oxidation and the urea cycle, branched-chain amino acids and biogenic amines
Metabolomics changes in urine
Time Frame: From baseline to week 12
Targeted and quantitative analysis by ultra-high-resolution liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ/MS). Analysis of specific families of metabolites selected from hypotheses generated by previous exploratory studies: changes in acylcarnitines and other intermediates of mitochondrial β-oxidation and the urea cycle, branched-chain amino acids and biogenic amines
Secondary Outcomes
- BMI (body mass index) changes(From baseline to to week 12)
- Changes in insulin resistance(From baseline to to week 12)
- Changes in Quality of Life: 36-Item Short Form Health Survey (SF-36) questionnaire(From baseline to to week 12)
- Changes in albuminuria(From baseline to to week 12)
- Changes in metabolic control(From baseline to to week 12)