The association between SGLT2 inhibitors and new-onset acute coronary syndrome in the elderly: a population-based longitudinal cohort study

Abstract

Background Several observational cohorts and meta-analytical studies on humans have shown that users of sodium-glucose cotransporter-2 inhibitors (SGLT2is) have a lower risk for new-onset acute coronary syndrome (ACS) than nonusers. However, some studies, including randomized clinical trials, reported the opposite results. This study aimed to investigate the impacts of a SGLT2i on new-onset ACS in a population. Methods We conducted a retrospective population-based cohort study involving 56,356 subjects who received SGLT2i therapy and 112,712 patients who did not receive SGLT2i therapy between May 1, 2016 and December 31, 2019. The outcome was the risk of new-onset ACS. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals for associations between SGLT2i use and ACS risk. Results A total of 670 and 1408 ACS events occurred in SGLT2i users and nonusers, respectively, during a follow-up of 3.7 years. SGLT2i use was associated with a nonsignificantly lower risk of ACS (adjusted HR 0.95, 95%confidence intervals (CI 0.87–1.04, P = 0.3218). We confirmed the robustness of these results through a propensity score 1:1 matching analysis. The results of the subgroup analysis of the subtype of the SGLT2i treatments were consistent with the main findings. An increased risk for the incidence of ACS in male and older (> 70 years) patients were also found. Conclusions In this population-based cohort study, we found that SGLT2i use is associated with a nonsignificantly decreased risk of ACS. No difference in the SGLT2i subtype was observed in subgroup analyses. However, the results of this study indicated an increased risk for the incidence of ACS in male and older (> 70 years) patients.

The Reasons for the Low Uptake of New Antidiabetic Drugs with Cardiovascular Effects—A Family Doctor Perspective

“…ref. [78] SGLT2-in use was associated with a non-significantly decreased risk of ACS. No difference in the SGLT2-in subtype was observed in subgroup analyses.…”

“…Although the common conclusion of the studies performed so far is that SGLT2-in and GLP-1ra improve CV outcomes in older (≥65) and frail patients, concerns remain when narrowly defined patient subgroups are used for the analysis such as older men and those older than 70 years [ 78 ]. In addition, frailty may change the harm–benefit balance of these drugs.…”

Compare SGLT2I versus non-SGLT2I users in type-2 diabetic mellitus patients on GLP-1 receptor agonist: A population-based and machine learning causal inference analysis

“…To reduce the risks of cardiovascular diseases, current clinical guidelines highlight the importance of a multifactorial approach in diabetic management, including the use of anti-diabetic agents [2,3]. The current literature suggests that novel anti-diabetic medications such as sodium-glucose cotransporter-2 inhibitors (SGLT2I) and glucagon-like peptide receptor agonists (GLP1a) demonstrate promising protective effects against various major adverse cardiovascular events (MACE) and mortality [4][5][6]. Some studies suggested that the cardiovascular benefit of SGLT2I and GLP1a is enhanced when used in conjunction [7].…”