The main aim of this study is to identify the underlying mechanisms of Sodium-glucose co-transporter-2 (SGLT2) inhibitors which are associated to better outcomes in patients with Diabetes mellitus type 2 and Heart Failure with preserved Ejection Fraction.

Double design study including a clinical trial and a nested case-control study.

A) Experimental study (clinical trial): Phase IV, prospective, randomized, double-blind placebo-controlled with 12 months follow-up. Inclusion criteria are: 1) diagnosis of DM2, 2) HF with preserved EF with a hospital admission in the previous 6 months with demonstration of diastolic dysfunction. 3) Stable clinical situation at inclusion. 4) Clinical indication of cardiac catheterization.

Patients will be randomized 1:1 to received Dapagliflozin 10 mg/day or placebo. The main objective is to compare the impact of the drug on LV diastolic properties at the peak of effort and in levels of plasma deposit and cross-linking biomarkers of type I collagen between the two treatment groups at baseline and after 12 months.

52 patients will be recruited.

B) Descriptive study: Nested case-control study, considering patients from the experimental study as cases and 10 additional patients with HF with preserved EF but no type 2 DM as controls. The main aim will be compare the histological, molecular, biochemical and biomechanical features of the HFpEF patients with and without DM2.

Inclusion Criteria:

• Diagnosis of DM2 based on the established criteria: HbA1c ≥ 6.5% (48 mmol / mol) and fasting plasma glucose ≥ 7.0 mmol / L (≥126 mg / dL) or 2-h after overload ≥ 11.1 mmol / L ( ≥ 200 mg / dL).
• LVEF ≥ 50%.
• Diagnosis of ICFEP according to clinical criteria, with a hospital admission in the previous 6 months with demonstration of diastolic dysfunction according to the echocardiographic criteria.
• Stable clinical situation (> 1 month after hospitalization due to IC decompensation).
• Clinical indication of cardiac catheterization.
• Signature of informed consent.

Exclusion Criteria:

• Previous treatment with iSGLT2.
• Significant coronary disease.
• Aortic or mitral valve disease ≥ moderate (grades 3 or 4/4 for valve regurgitations)
• Contraindications for dapagliflozin treatment according to the data sheet (hereditary galactose intolerance, Lapp lactase insufficiency or glucose-galactose malabsorption, moderate-severe renal failure -CrCl <60 ml / min or eGFR <60 ml / min / 1 , 73 m2-, severe hepatic insufficiency).

The inclusion/exclusion criteria for Descriptive Study will be the same as previously described without the diagnosis of DM2.