Association between serum insulin levels and heart failure-related parameters in patients with type 2 diabetes and heart failure treated with canagliflozin: a post-hoc analysis of the randomized CANDLE trial

Background Insulin resistance and hyperinsulinemia in patients with type 2 diabetes (T2D) are adversely associated with the development and worsening of heart failure (HF). Herein, we sought to investigate the effect of canagliflozin on insulin concentrations and the associations of changes in insul...

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Published in:Cardiovascular diabetology 2022-08, Vol.21 (1), p.1-151, Article 151
Main Authors: Tanaka, Atsushi, Imai, Takumi, Shimabukuro, Michio, Taguchi, Isao, Sezai, Akira, Toyoda, Shigeru, Watada, Hirotaka, Ako, Junya, Node, Koichi
Format: Article
Language:English
Subjects:
Antidiabetics
Canagliflozin
Chronic heart failure
Congestive heart failure
Diabetes
Diabetes mellitus (non-insulin dependent)
Fasting
Glimepiride
Glucose
Heart failure
Hyperinsulinemia
Insulin
Insulin resistance
Laboratories
Metabolism
Patients
Plasma
Regression analysis
Type 2 diabetes
Ventricle
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Summary:Background Insulin resistance and hyperinsulinemia in patients with type 2 diabetes (T2D) are adversely associated with the development and worsening of heart failure (HF). Herein, we sought to investigate the effect of canagliflozin on insulin concentrations and the associations of changes in insulin concentrations with HF-related clinical parameters in patients with T2D and HF. Methods This was a post-hoc analysis of the investigator-initiated, multicenter, open-label, randomized, controlled CANDLE trial for patients with T2D and chronic HF (UMIN000017669). The endpoints were the effects of 24 weeks of canagliflozin treatment, relative to glimepiride treatment, on insulin concentrations and the relationship between changes in insulin concentrations and clinical parameters of interest, including New York Heart Association (NYHA) classification. The effects of canagliflozin on those parameters were also analyzed by baseline insulin level. Results Among the participants in the CANDLE trial, a total of 129 patients (canagliflozin, n = 64; glimepiride, n = 65) who were non-insulin users with available serum insulin data both at baseline and week 24 were included in this analysis. Overall, the mean age was 69.0 ± 9.4 years; 75% were male; the mean HbA1c was 6.8 ± 0.7%; and the mean left ventricular ejection fraction was 59.0 ± 14.1%, with parameters roughly balanced between treatment groups. Canagliflozin treatment significantly reduced insulin concentrations at week 24 (p 
ISSN:1475-2840
1475-2840
DOI:10.1186/s12933-022-01589-3