Abstract
BackgroundBecause type 2 diabetes mellitus is associated strongly with an increased risk of cardiovascular diseases, the number of patients with diabetes with chronic heart failure is increasing steadily. However, clinical evidence of therapeutic strategies in such patients is still lacking. A recent randomized, placebo-controlled trial in patients with type 2 diabetes with high cardiovascular risk demonstrated that the SGLT2 inhibitor, empagliflozin, reduced the incidence of hospitalization for heart failure. Because SGLT2 inhibitors cause a reduction in body weight and blood pressure in addition to improving glycemic control, they have the potential to exert beneficial effects on the clinical pathophysiology of heart failure. The aim of the ongoing CANDLE trial is to test the safety and non-inferiority of canagliflozin, another SGLT2 inhibitor, compared with glimepiride, a sulfonylurea agent, in patients with type 2 diabetes mellitus and chronic heart failure.MethodsA total of 250 patients with type 2 diabetes who are drug-naïve or taking any anti-diabetic agents and suffering from chronic heart failure with a New York Heart Association classification I to III will be randomized centrally into either canagliflozin or glimepiride groups (1: 1) using the dynamic allocation method stratified by age (<65, ≥65 year), HbA1c level (<6.5, ≥6.5 %), and left ventricular ejection fraction (<40, ≥40 %). After randomization, all the participants will be given the add-on study drug for 24 weeks in addition to their background therapy. The primary endpoint is the percentage change from baseline in NT-proBNP after 24 weeks of treatment. The key secondary endpoints after 24 weeks of treatment are the change from baseline in glycemic control, blood pressure, body weight, lipid profile, quality of life score related to heart failure, and cardiac and renal function.DiscussionThe CANDLE trial is the first to assess the safety and non-inferiority of canagliflozin in comparison with glimepiride in patients with type 2 diabetes with chronic heart failure. This trial has the potential to evaluate the clinical safety and efficacy of canagliflozin on heart failure.Trial registration Unique trial Number, UMIN000017669Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0381-x) contains supplementary material, which is available to authorized users.
Highlights
Because type 2 diabetes mellitus is associated strongly with an increased risk of cardiovascular dis‐ eases, the number of patients with diabetes with chronic heart failure is increasing steadily
type 2 diabetes mellitus (T2DM) patients with severe chronic heart failure (CHF) with a New York Heart Association (NYHA) functional classification of III and IV were excluded from these trials, because the use of Sodium glucose co-transporter 2 (SGLT2) inhibitors is not clinically recommended in these patients
The CANDLE trial is an ongoing, multicenter, prospective, randomized, investigator-initiated clinical trial that has the aim of testing the safety and non-inferiority of canagliflozin in T2DM patients with CHF
Summary
Because type 2 diabetes mellitus is associated strongly with an increased risk of cardiovascular dis‐ eases, the number of patients with diabetes with chronic heart failure is increasing steadily. Co-morbidities associated with type 2 diabetes mellitus (T2DM) are increasing steadily in patients with chronic heart failure (CHF). Their prevalence was reported to be 30 % in the JCARE-CARD trial and 23 % in the CHART-2 trial [1, 2]. Complications of T2DM aggravate clinical outcomes, such as higher mortality, morbidity, and re-hospitalization rate for worsening heart failure in patients with CHF. This indicates that T2DM is a relatively strong risk factor for CHF [3, 4]. The Japan Diabetes Society has not described specific treatment options for diabetes in patients with CHF, lowering HbA1c levels to
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
