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Sodium-glucose co-transporter-2 inhibitors in patients treated with immune checkpoint inhibitors

  • Moran Gvili Perelman,
  • Rafael Y. Brzezinski,
  • Barliz Waissengrin,
  • Yasmin Leshem,
  • Or Bainhoren,
  • Tammi Arbel Rubinstein,
  • Maxim Perelman,
  • Zach Rozenbaum,
  • Ofer Havakuk,
  • Yan Topilsky,
  • Shmuel Banai,
  • Ido Wolf,
  • Michal Laufer-Perl

摘要

Background

Immune checkpoint inhibitors (ICIs) have revolutionized the prognosis of cancer. Diabetes mellitus (DM) has been shown to have a negative effect on patients treated with ICIs. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective antidiabetic therapies associated with reduced all-cause mortality and cardiovascular (CV) outcomes.

Objective

To evaluate the prognostic value of SGLT2i on all-cause mortality and cardiotoxicity among patients treated with ICIs.

Methods

We performed a retrospective analysis of patients diagnosed with cancer and type 2 DM (DM2) and treated with ICIs at our center. Patients were divided into two groups according to baseline treatment with or without SGLT2i. The primary endpoint was all-cause mortality and the secondary endpoint was MACE, including myocarditis, acute coronary syndrome, heart failure, and arrhythmia.

Results

The cohort included 119 patients, with 24 (20%) patients assigned to the SGLT2i group. Both groups exhibited a comparable prevalence of cardiac risk factors, although the SGLT2i group displayed a higher incidence of ischemic heart disease. Over a median follow-up of 28 months, 61 (51%) patients died, with a significantly lower all-cause mortality rate in the SGLT2i group (21% vs. 59%, p = 0.002). While there were no significant differences in MACE, we observed zero cases of myocarditis and atrial fibrillation in the SGLT2i, compared to 2 and 6 cases in the non-SGLT2i group.

Conclusions

SGLT2i therapy was associated with a lower all-cause mortality rate in patients diagnosed with cancer and DM2 and treated with ICIs. Further studies are needed to understand the mechanism and evaluate its benefit on cardiotoxicity.

Graphical Abstract