Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents

Cardiovascular Diabetology

Arihiro Kiyosue¹  Takahiro Okumura²  Yumiko Kanzaki³  Kazuki Shiina⁴  Hirofumi Tomiyama⁴  Shigeru Toyoda⁵  Yasushi Sakata⁶  Koichi Node⁷  Atsushi Tanaka⁷  Takumi Imai⁸  Masami Nishino⁹  Yasushi Matsuzawa^1,10  Katsuya Onishi^1,11 

[1] Department of Cardiology, Moriyama Memorial Hospital, Tokyo, Japan;Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan;Department of Cardiology, Osaka Medical and Pharmaceutical University, Takatsuki, Japan;Department of Cardiology, Tokyo Medical University, Tokyo, Japan;Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, Mibu, Japan;Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan;Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, 849-8501, Saga, Japan;Department of Medical Statistics, Graduate School of Medicine, Osaka City University, Osaka, Japan;Division of Cardiology, Osaka Rosai Hospital, Sakai, Japan;Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan;Onishi Heart Clinic, Tsu, Japan;

关键词: Type 2 diabetes;    Chronic heart failure;    Sodium–glucose cotransporter 2 inhibitor;    Metformin;    Dipeptidyl peptidase-4 inhibitor;   

DOI  :  10.1186/s12933-021-01369-5

来源: Springer

【 摘 要 】

BackgroundSodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of a deterioration in heart failure (HF) and mortality in patients with a broad range of cardiovascular risks. Recent guidelines recommend considering the use of SGLT2 inhibitors in patients with type 2 diabetes (T2D) and HF, irrespective of their glycemic control status and background use of other glucose-lowering agents including metformin. However, only a small number of studies have investigated whether the effects of SGLT2 inhibitor in these patients differ by the concomitant use of other glucose-lowering agents.MethodsThis was a post-hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. The primary aim of the analysis was to assess the effect of 24 weeks of treatment with canagliflozin, relative to glimepiride, on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with T2D and clinically stable chronic HF. In the present analysis, the effect of canagliflozin on NT-proBNP concentration was assessed in the patients according to their baseline use of other glucose-lowering agents.ResultsAlmost all patients in the CANDLE trial presented as clinically stable (New York Heart Association class I to II), with about 70% of participants having HF with a preserved ejection fraction phenotype (defined as a left ventricular ejection fraction ≥ 50%) at baseline. Of the 233 patients randomized to either canagliflozin (100 mg daily) or glimepiride (starting dose 0.5 mg daily), 85 (36.5%) had not been taking any glucose-lowering agents at baseline (naïve). Of the 148 patients who had been taking at least one glucose-lowering agent at baseline (non-naïve), 44 (29.7%) and 127 (85.8%) had received metformin or a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, respectively. The group ratio (canagliflozin vs. glimepiride) of proportional changes in the geometric means of NT-proBNP concentration was 0.95 (95% confidence interval [CI] 0.76 to 1.18, p = 0.618) for the naïve subgroup, 0.92 (95% CI 0.79 to1.07, p = 0.288) for the non-naïve subgroup, 0.90 (95% CI 0.68 to 1.20, p = 0.473) for the metformin-user subgroup, and 0.91 (95% CI 0.77 to 1.08, p = 0.271) for the DPP-4 inhibitor-user subgroup. No heterogeneity in the effect of canagliflozin, relative to glimepiride, on NT-proBNP concentration was observed in the non-naïve subgroups compared to that in the naïve subgroup.ConclusionThe impact of canagliflozin treatment on NT-proBNP concentration appears to be independent of the background use of diabetes therapy in the patient population examined.Trial registration University Medical Information Network Clinical Trial Registry, number 000017669. Registered on May 25, 2015

【 授权许可】

CC BY