Vol 30, No 1 (2023)
Research Letter
Published online: 2023-01-30

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Sodium-glucose cotransporter 2 inhibitors in obese patients with heart failure

Shingo Kato12, Nobuyuki Horita3, Daisuke Utsunomiya2
Pubmed: 36790045
Cardiol J 2023;30(1):153-154.

Abstract

Not available

clinicAL CARDIOLOGY

research letter

Cardiology Journal

2023, Vol. 30, No. 1, 153–154

DOI: 10.5603/CJ.a2023.0004

Copyright © 2023 Via Medica

ISSN 1897–5593

eISSN 1898–018X

Sodium-glucose cotransporter 2 inhibitors in obese patients with heart failure

Shingo Kato12Nobuyuki Horita3Daisuke Utsunomiya2
1Department of Cardiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan
2Department of Diagnostic Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
3Chemotherapy Center, Yokohama City University Hospital, Yokohama, Japan

Address for correspondence: Shingo Kato, MD, PhD, Department of Diagnostic Radiology, Yokohama City University
Graduate School of Medicine, Yokohama, Japan, tel: +81 45 701 9581, fax: +81 45 786 4770,
e-mail:
sk513@yokohama-cu.ac.jp

Received: 4.07.2022 Accepted: 18.11.2022 Early publication date: 30.01.2023

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.

While obesity increases the risk of heart failure (HF), the prognosis of obese HF patients is better than that of non-obese HF patients. This phenomenon is called the “obesity paradox” [1]. This may explain why pharmacotherapy of various HF conditions may differ in obese than to non-obese HF patients. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to improve the prognosis of HF patients regardless of left ventricular contractility; SGLT-2 inhibitors are pivotal agents that have created a new paradigm shift in the pharmacological treatment of HF. Four large randomized controlled trials (RCTs) have been conducted to date, and in a sub-analysis of body mass index (BMI), there is a slight difference in the prognostic improvement effect of SGLT-2 [2–5]. It is hypothesized herein, that there might be a difference in the efficacy of SGLT-2 according to high and low BMI. To test this hypothesis, a meta-analysis of four large RCTs was performed. Four large RCTs (> 1000 patients) were analyzed with data from sub-analyses stratified by BMI (< 30 kg/m2 or > 30 kg/m2) [2–5]. Obesity was defined as BMI ≥ 30 kg/m2. A total of 20.717 HF patients were analyzed, including 8.318 (40%) obese patients; 2 RCT used empagliflozin [2, 4], and other 2 RCT used dapagliflozin [3, 5]. Hazard ratio (HR) for primary end-point (cardiovascular death or hospitalization for HF) was pooled using the random-model generic inverse variance method after logarithm conversion (RevMan ver 5.4. Cochrane Collaboration, London, UK). Figure 1 demonstrates the results of a pooled meta-analysis. Treatment with SGLT-2 inhibitors resulted in a significant reduction in the primary end-point both in HF patients without obesity (HR: 0.78, 95% confidence interval [CI]: 0.70–0.88, p < 0.001, I2 = 32%, p for heterogeneity = 0.22), and HF patients with obesity (HR: 0.78, 95% CI: 0.73–0.83, p < 0.001, I2 = 4%, p for heterogeneity = 0.41). The effect of the SGLT-2 inhibitor was similar between HF patients with obesity and those without (p = 0.42) (Fig. 1).

Figure 1. The hazard ratio of composite cardiac events stratified by the presence or absence of obesity; CI — confidence interval; SE — standard error; SGLTi — sodium-glucose co-transporter-inhibitor.

The precise pathophysiology of the “obesity paradox” remains unclear. Possible mechanisms are the cardioprotective effect of various cytokines and neuroendocrine profiles, increased muscle mass and strength, higher blood pressure leading to more cardiac medications, and other factors [1]. Although the mechanism is not well-understood, epidemiological studies demonstrated that survival rates were better in obese HF patients than in low--weight HF patients. Therefore, confirmation of the effect of SGLT-2 inhibitor both for obese and non- -obese HF patients might be clinically meaningful. In addition, two large-scale RCTs were included using empagliflozin in the meta-analysis and demonstrated that the effect did not vary according to BMI, similar to dapagliflozin. The present data will contribute to considering the indication of SGLT-2 inhibitor for HF patients with obesity.

However, it must be recognized that there are several caveats in the interpretation of the results of this meta-analysis. The integration of data from two different SGLT-2 inhibitors, i.e., to conclude that there is a class effect of SGLT-2 inhibitors in obese patients, further meta-analysis using different SGLT-2 inhibitors or comparing dapagliflozin and empagliflozin trials would be needed to conclude that there is a class effect of SGLT-2 inhibitors in obese patients. The results of the current study only mention the potential of SGLT-2 as a whole to improve the prognosis of HF patients regardless of BMI value. Understanding these limitations, we should continue to monitor new evidence on SGLT-2 inhibitors.

Conflict of interest: None declared

References

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