Review on the use of Sodium-glucose transporter 2 inhibitors and Glucagon-like peptide 1 agonists in people with type 2 diabetes mellitus and cardiovascular disease

Abstract

Introduction: Introduction: Type 2 diabetes mellitus is an important and growing health problem worldwide. Objective: This study aims to evaluate the quality of the evidence available on sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonists in people with diabetes mellitus and atherosclerotic cardiovascular disease. Methods: This integrative review was performed using the following databases: MEDLINE via PubMed, Embase via Cochrane Library, Cochrane Library, LILACS via VHL. The research question was structured as follows: population – people with type 2 diabetes mellitus and established cardiovascular disease; intervention – usual treatment, except insulin + sodium-glucose cotransporter 2 inhibitors or usual treatment, except insulin + and glucagon-like peptide 1 agonists; control – usual treatment, except insulin + placebo; outcome – overall mortality, mortality from cardiovascular causes, morbidity, adverse effects. Results: Two studies on empagliflozin were selected. This drug associated with the usual treatment was superior to placebo associated with the usual treatment in the primary outcome (hazard ratio — HR 0.86; 95% confidence interval — 95%CI 0.74–0.99; p=0.04), in reducing heart failure hospitalization (HR 0.65; 95%CI 0.50–0.85; p=0.002), in cardiovascular mortality (HR 0.62; 95%CI 0.49–0.77), and in overall mortality (HR 0.68; 95%CI 0.57–0.82; p<0.001). The subgroup of people with diabetes who were not on insulin benefited from using empagliflozin concerning the primary outcome (HR 0.79; 95%CI 0.64–0.97; risk difference — RD 2.5; number needed to treat — NNT 40) and cardiovascular mortality (HR 0.61; 95%CI 0.44–0.85; RD 2; NNT 49). The analysis of the subgroups showed heterogeneity. Participants aged 65 years or older (p=0.01) and those with glycated hemoglobin lower than 8.5 benefited from empagliflozin in the primary outcome. A difference (p=0.05) related to cardiovascular mortality was found, with the use of empagliflozin reducing the risk only in the subgroup with body mass index <30. No significant difference was identified with respect to placebo for fatal and nonfatal stroke nor for the composite outcome of nonfatal disabling stroke and fatal stroke (HR 0.81; 95%CI 0.43–1.50; p=0.50). More people had strokes in the intervention group in which the initial glycated hemoglobin was ≥8.5%, favoring placebo (p=0.01). Conclusions: The data found suggest the benefit of the Brazilian public health system using this drug in people with cardiovascular diseases. However, the population groups were heterogeneous, which may help outline strategies for using these medications. Further studies are necessary to assess why isolated cerebrovascular outcomes showed no benefit.