Safety and Effectiveness of SGLT-2 Inhibitors in Patients With Heart Failure and Diabetes

Men and women with diabetes have a 2-5-fold increased risk of heart failure (HF). The prevalence and incidence of HF is increasing in diabetes and mortality rates remain alarmingly high. This highlights the need for novel therapies in diabetes that will reduce HF risk and /or delay disease progression.

Drug options are currently limited as some diabetic therapies such as thiazolidinediones are contra-indicated in HF. SGLT2 inhibitors, the newest class of anti-diabetic drugs, are an exciting new approach to diabetes management that may have additional beneficial effects in diabetes and HF. SGLT2 inhibitors may have beneficial effects on adverse left ventricular (LV) remodelling that occurs in patients with diabetes and heart failure by reducing the load on the heart through its diuretic and blood pressure lowering actions.

Exercise intolerance is a cardinal symptom of patients with HF and improving insulin sensitivity has been shown to improve exercise capacity. SGLT2 inhibition has been shown to improve insulin sensitivity and to reduce weight and therefore has the potential to improve exercise capacity in HF.

This study will assess the potential beneficial effects of the oral SGLT2 inhibitor, dapagliflozin, on LV remodelling and exercise capacity in patients with diabetes and HF. The findings of this study may help to establish the utility of SGLT2 inhibitors in diabetic patients with HF and provide important clinical data on the impact of SGLT2 inhibition on LV remodelling.

Inclusion criteria

• were previously diagnosed with Type 2 Diabetes
• are diagnosed with NYHA functional class I-III HF with prior echocardiographic evidence of Left Ventricular Systolic Dysfunction (LVSD) (At least mild LV systolic dysfunction on sonographer assessment or ejection fraction at 45% or less)
• on furosemide 80mg daily or less, or equivalent loop diuretic
• have stable HF symptoms for at least three months prior to consent
• on stable therapy for HF for at least three months prior to consent
• have not been hospitalised for HF for at least three months prior to consent

Exclusion criteria

• severe hepatic disease
• renal disease defined as Chronic Kidney Disease (CKD) class 3b or worse (i.e. estimated glomerular filtration rate (eGFR) / creatinine clearance CrCl <45ml/min)
• systolic BP <95mmHg at screening visit
• screening HbA1c <6.0%
• unable to walk to perform cardio pulmonary exercise testing or 6MWT
• malignancy (receiving active treatment) or other life threatening diseases
• pregnant or lactating women
• any contraindication to MRI (e.g. claustrophobia, metal implants, penetrative eye injury or exposure to metal fragments in eye requiring medical attention)
• patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days
• patients who are unable to give informed consent
• any other reason considered by a study physician to be inappropriate for inclusion.