Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists and cancer mortality. A real-world registry
Authors: Garcia Vega D , Cinza-Sanjurjo S , Tilves-Bellas C , Eiras S , Gonzalez-Juanatey J R 
Published: October 2024

Abstract

Background
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce cardiovascular events through different mechanisms, nevertheless, their association with cancer remains unclear.

Purpose
We aim to compare the combined treatment (SGLT2i and GLP1ra) with monotherapy regarding hospitalization or/and death for cancer in a general population and a subgroup of patients with cardiovascular disease (CVD).

Methods
Retrospective observational study of patients who were prescribed SGLT2i, GLP1ra, or both drugs. Multinomial propensity score was performed in all the population and in a subgroup of patients with CVD (atrial fibrillation [AF], heart failure [HF], coronary artery disease [CAD], peripheral arterial disease [PAD], or cerebrovascular accident [CVA]). The following variables were included to adjust the three groups: Sex, Age, Obesity, diabetes mellitus (DM), high blood pressure (HBP), dyslipidemia (DLP), CAD, HF, AF, and CVA. The three primary outcomes were (i) hospitalization for any cancer, (ii) death for any cancer, and (iii) the combined event in the included population and the subgroup of patients with CVD. The multivariate Cox regression analysis determined the hazard rate (HR) of age, sex, risk factors, and treatment for each outcome.

Results
We included 14709 patients (11366 with SGLT2i, 1016 with GLP1ra, and 2327 with both treatments) from the treatment initiation. The subgroup with CVD included 4957 (33.7%) patients (Fig 1). After 33 months of median follow-up, the incidence of cancer events was similar between patients with and without CVD (3.4% or 3.7%, respectively). Sex (male) and age were the main risk factors for the 3 outcomes in both groups. Combined treatment and its duration had a protector role for cancer mortality regarding monotherapy with SGLT2i or GLP1ra in all population (HR [95%CI]) 0.2216 [0.106-0.459]; p&lt;0.001 or 0.1928 [0.071-0.519]; p=0.001, respectively) (Fig 2a) and in the subgroup of patients with CVD (HR [95%CI]) 0.279 [0.078-0.994]; p&lt;0.049 or 0.129 [0.024-0.668]; p=0.014, respectively) (Fig 2b), but these results were not found for the outcome of hospitalization for cancer. The combined therapy concerning SGLT2i and duration of treatment showed a protective role against the combined event (HR [95%CI]) 0.709 [0.521-0.967]; p=0.029) and (HR [95%CI]) 0.991 [0.983-0.999]; p=0.032) in the general population but not in the group of CVD. A higher survival rate for any cancer mortality was observed in those patients with the combined therapy respect to monotherapy (SGLT2i or GLP1ra) in the general population (Fig 2c) and the subgroup of patients with CVD (Fig 2d).

Conclusions
Initiation of combined therapy vs. monotherapy was associated with a lower rate of cancer mortality in the general population and patients with CVD. Future clinical trials and mechanistic studies will clarify the possible role of these drugs on carcinogenesis.Figure 1Figure 2