Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline. Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function. The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89–1.08) in the canagliflozin group and 1.07 (95% CI 0.97–1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82–1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e′) showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e′ < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66–1.04). In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.

中文翻译：

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卡格列净对 2 型糖尿病合并慢性心力衰竭患者左心室舒张功能分层 NT-proBNP 的影响：CANDLE 试验的子分析

确定心力衰竭 (HF) 治疗的有效亚型是优化该疾病治疗的重要课题。我们假设 SGLT2 抑制剂 (SGLT2i) 对 N 端脑利钠肽前体 (NT-proBNP) 水平的有益作用可能取决于基线舒张功能。为了阐明 SGLT2i 在 2 型糖尿病 (T2DM) 和慢性 HF 中的作用，我们调查了作为 CANDLE 试验的事后子研究，从基线到 24 周，卡格列净对 NT-proBNP 水平的影响，在基线时按左心室 (LV) 舒张功能分层的数据。CANDLE 试验中的患者 (n = 233) 被随机分配到附加卡格列净 (n = 113) 或格列美脲治疗组 (n = 120)。主要终点是比较两组从基线到 24 周 NT-pro BNP 水平的变化，根据基线心室舒张功能分层。卡格列净组 NT-proBNP 水平从基线到 24 周的几何平均值变化为 0.98（95% CI 0.89-1.08），格列美脲组为 1.07（95% CI 0.97-1.18）。卡格列净/格列美脲的变化比为 0.93（95% CI 0.82–1.05）。反应者分析用于调查 NT-proBNP 水平改善的反应。尽管对间隔环速度 (SEP-e') 的亚组分析显示治疗效果没有明显的异质性，但 SEP-e' < 4 的亚组。