PMID- 35941584
OWN - NLM
STAT- MEDLINE
DCOM- 20220810
LR  - 20220827
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 21
IP  - 1
DP  - 2022 Aug 8
TI  - 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.
PG  - 151
LID - 10.1186/s12933-022-01589-3 [doi]
LID - 151
AB  - 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 < 0.001), and the between-group difference (canagliflozin minus glimepiride) 
      in those changes was - 3.52 mU/L (95% confidence interval, - 4.85 to - 2.19; 
      p < 0.001). Decreases in insulin concentrations, irrespective of baseline insulin 
      level, were significantly associated with improvement in NYHA class in patients 
      treated with canagliflozin. CONCLUSION: Our findings suggest that canagliflozin 
      treatment in patients with T2D and HF ameliorated excess insulin overload, 
      contributing to the improvement of clinical HF status. TRIAL REGISTRATION: 
      University Medical Information Network Clinical Trial Registry, number 000017669, 
      Registered on May 25, 2015.
CI  - (c) 2022. The Author(s).
FAU - Tanaka, Atsushi
AU  - Tanaka A
AD  - Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 
      849-8501, Japan. tanakaa2@cc.saga-u.ac.jp.
FAU - Imai, Takumi
AU  - Imai T
AD  - Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan 
      University, Osaka, Japan.
FAU - Shimabukuro, Michio
AU  - Shimabukuro M
AD  - Department of Diabetes, Endocrinology, and Metabolism, Fukushima Medical 
      University, Fukushima, Japan.
FAU - Taguchi, Isao
AU  - Taguchi I
AD  - Department of Cardiology, Dokkyo Medical University Saitama Medical Center, 
      Koshigaya, Japan.
FAU - Sezai, Akira
AU  - Sezai A
AD  - Department of Cardiovascular Surgery, Nihon University School of Medicine, Tokyo, 
      Japan.
FAU - Toyoda, Shigeru
AU  - Toyoda S
AD  - Department of Cardiovascular Medicine, Dokkyo Medical University School of 
      Medicine, Mibu, Japan.
FAU - Watada, Hirotaka
AU  - Watada H
AD  - Department of Metabolism & Endocrinology, Juntendo University Graduate School of 
      Medicine, Tokyo, Japan.
FAU - Ako, Junya
AU  - Ako J
AD  - Department of Cardiovascular Medicine, Kitasato University School of Medicine, 
      Sagamihara, Japan.
FAU - Node, Koichi
AU  - Node K
AD  - Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 
      849-8501, Japan. node@cc.saga-u.ac.jp.
CN  - CANDLE trial investigators
LA  - eng
SI  - UMIN-CTR/UMIN000017669
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20220808
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0SAC974Z85 (Canagliflozin)
SB  - IM
MH  - Aged
MH  - Blood Glucose
MH  - Canagliflozin/adverse effects
MH  - *Diabetes Mellitus, Type 2/diagnosis/drug therapy
MH  - Female
MH  - *Heart Failure/chemically induced/diagnosis/drug therapy
MH  - Humans
MH  - Insulin/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Stroke Volume
MH  - Treatment Outcome
MH  - Ventricular Function, Left
PMC - PMC9358857
OTO - NOTNLM
OT  - Canagliflozin
OT  - Chronic heart failure
OT  - Glimepiride
OT  - Insulin
OT  - Type 2 diabetes
COIS- AT received honoraria from Boehringer Ingelheim and research funding from 
      GlaxoSmithKline and Takeda. TI received lecture fees from JCR Pharmaceuticals and 
      Kyowa Kirin and outsourcing fees from Organization for Clinical Medicine 
      Promotion. MS received honoraria from Mitsubishi Tanabe. ST received honoraria 
      from Ono, Bayer, Novartis, Otsuka, Daiichi Sankyo, and AstraZeneca and research 
      funding from Boston Scientific. HW has received honoraria for lectures from 
      Mitsubishi Tanabe, Sumitomo Dainippon, Sanwa Kagaku Kenkyusyo, Takeda, Sanofi, 
      Kowa, MSD, Nippon Boehringer Ingelheim, Eli Lilly, Novo Nordisk, AstraZeneca, 
      Ono, Astellas, Kyowa Kirin, Terumo, Taisho, Abbott Japan, and Kissei and research 
      grants from Mitsubishi Tanabe, Takeda, Nippon Boehringer Ingelheim, Kissei, Novo 
      Nordisk, Kyowa Kirin, Eli Lilly, Taisho, Astellas, Ono, Sanofi, MSD, Kowa, 
      LifeScan Japan, Teijin, Daiichi Sankyo, Sumitomo Dainippon, and Sanwa Kagaku 
      Kenkyusyo. JA received speaking honoraria from Mitsubishi Tanabe, Boehringer 
      Ingelheim, and Astra Zeneca. KN has received honoraria from Astellas, 
      AstraZeneca, Bayer, Boehringer Ingelheim Japan, Daiichi Sankyo, Eli Lilly Japan, 
      Kowa, Mitsubishi Tanabe, Mochida, MSD, Novartis, Ono, Otsuka, Takeda, and 
      Tsumura, research grants from Asahi Kasei, Astellas, Boehringer Ingelheim Japan, 
      Fuji, Mitsubishi Tanabe, Mochida, Novartis, and Teijin and scholarship from 
      Bayer, Daiichi Sankyo, Takeda, Teijin, and Japan Lifeline. All other authors 
      declare no competing interests.
EDAT- 2022/08/09 06:00
MHDA- 2022/08/11 06:00
PMCR- 2022/08/08
CRDT- 2022/08/08 23:46
PHST- 2022/03/26 00:00 [received]
PHST- 2022/08/01 00:00 [accepted]
PHST- 2022/08/08 23:46 [entrez]
PHST- 2022/08/09 06:00 [pubmed]
PHST- 2022/08/11 06:00 [medline]
PHST- 2022/08/08 00:00 [pmc-release]
AID - 10.1186/s12933-022-01589-3 [pii]
AID - 1589 [pii]
AID - 10.1186/s12933-022-01589-3 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2022 Aug 8;21(1):151. doi: 10.1186/s12933-022-01589-3.