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. 2024 Sep 22;6(6):863-875.
doi: 10.1016/j.jaccao.2024.08.001. eCollection 2024 Dec.

SGLT2i and Primary Prevention of Cancer Therapy-Related Cardiac Dysfunction in Patients With Diabetes

Ammar W Bhatti  1 , Rushin Patel  1 , Sourbha S Dani  1 , Sumanth Khadke  1 , Bhargav Makwana  1 , Candace Lessey  1 , Jui Shah  1 , Zaid Al-Husami  1 , Eric H Yang  2 , Paaladinesh Thavendiranathan  3 , Tomas G Neilan  4 , Diego Sadler  5 , Richard K Cheng  6 , Susan F Dent  7 , Jennifer Liu  8 , Teresa Lopez-Fernandez  9   10 , Joerg Herrmann  11 , Marielle Scherrer-Crosbie  12 , Daniel J Lenihan  13 , Salim S Hayek  14 , Bonnie Ky  15 , Anita Deswal  16 , Ana Barac  17 , Anju Nohria  18 , Sarju Ganatra  1
Affiliations

SGLT2i and Primary Prevention of Cancer Therapy-Related Cardiac Dysfunction in Patients With Diabetes

Ammar W Bhatti et al. JACC CardioOncol. .

Abstract

Background: Specific cancer treatments can lead to cancer therapy-related cardiac dysfunction (CTRCD). Sodium glucose cotransporter-2 inhibitors (SGLT2is) can potentially prevent these cardiotoxic effects.

Objectives: This study sought to determine whether SGLT2i use is associated with a lower incidence of CTRCD in patients with type 2 diabetes mellitus (T2DM) and cancer, exposed to potentially cardiotoxic antineoplastic agents, and without a prior documented history of cardiomyopathy or heart failure.

Methods: We conducted a retrospective analysis of patients aged ≥18 years within the TriNetX database with T2DM, cancer, exposure to cardiotoxic therapies, and no prior documented history of cardiomyopathy or heart failure. Patients were categorized by SGLT2i use. After propensity score matching, outcomes were compared over 12 months using Cox proportional HRs. Subgroup analyses focusing on different cancer therapy classes were performed.

Results: The study included 8,675 propensity-matched patients in each cohort (mean age = ∼65 years, 42% females, 71% White, ∼19% gastrointestinal malignancy, and ∼25% anthracyclines). Patients prescribed SGLT2is had a lower risk of developing CTRCD (HR: 0.76: 95% CI: 0.69-0.84). SGLT2is also reduced heart failure exacerbations (HR: 0.81; 95% CI: 0.72-0.90), all-cause mortality (HR: 0.67; 95% CI: 0.61-0.74), and all-cause hospitalizations/emergency department visits (HR: 0.93; 95% CI: 0.89-0.97). Subgroup analyses also demonstrated reduced CTRCD risk across various classes of cancer therapies in patients prescribed SGLT2is.

Conclusions: SGLT2i administration was associated with a significantly decreased risk of developing CTRCD in patients with T2DM and cancer.

Keywords: CTRCD; antineoplastic therapy; cardiomyopathy; primary prevention; sodium glucose co-transporter 2 inhibitors.

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Conflict of interest statement

Dr Yang has received research funding from CSL Behring (nonrelevant), Boehringer Ingelheim and Eli and Lilly, Amgen (nonrelevant), and Bristol Meyers Squibb (nonrelevant); and has received consulting fees from Xencor (nonrelevant). Dr Deswal has received consulting fees from Bayer. Dr Herrmann has received consulting fees from Pfizer, Astellas, and AstraZeneca; and has received grant funding from the National Institutes of Health (RO1 CA233610) and the Miami Heart Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Forest Plot for Subgroup Analysis Forest plot showing HRs and their corresponding 95% CIs for a subgroup analysis of the class of antineoplastic therapy and the risk of developing cancer therapy–related cardiac dysfunction while on sodium glucose co-transporter 2 inhibitor (SGLT2i). Ab = antibody; SGLT2 = sodium glucose co-transporter 2; TKI = tyrosine kinase inhibitor.
Figure 2
Figure 2
Kaplan-Meier Curve for Heart Failure Exacerbation A graph depicting the Kaplan-Meier curve for heart failure exacerbations for patients on sodium glucose co-transporter 2 inhibitor (SGLT2i) vs no SGLT2i.
Figure 3
Figure 3
Kaplan-Meier Curve for CTRCD A graph depicting the Kaplan-Meier curve for cancer therapy–related cardiac dysfunction–free survival for patients on sodium glucose co-transporter 2 inhibitor (SGLT2i) vs no SGLT2i.
Central Illustration
Central Illustration
Sodium Glucose Co-Transporter 2 Inhibitors in the Prevention of Cancer Therapy–Related Cardiac Dysfunction This figure presents the results of a propensity score–matched analysis involving adults with cancer and type 2 diabetes mellitus who did not have a previous history of cardiomyopathy or heart failure. It examines their exposure to potentially cardiotoxic antineoplastic therapies and the incidence of cancer therapy–related cardiac dysfunction (CTRCD) based on whether or not patients were taking sodium glucose co-transporter 2 inhibitor (SGLT2i). Ab = antibody; SGLT2 = sodium glucose co-transporter 2; TKI = tyrosine kinase inhibitor.
Figure 4
Figure 4
Kaplan-Meier Curve for All-Cause Mortality A graph depicting the Kaplan-Meier curve for all-cause mortality for patients on sodium glucose co-transporter 2 inhibitor (SGLT2i) vs no SGLT2i.
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