Abstract
Type 2 diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Atrial fibrillation (AF) and stroke are both forms of CVD that have major consequences in terms of disabilities and death among patients with diabetes; however, they are less present in the preoccupations of scientific researchers as a primary endpoint of clinical trials. Several publications have found DM to be associated with a higher risk for both AF and stroke; some of the main drugs used for glycemic control have been found to carry either increased, or decreased risks for AF or for stroke in DM patients. Given the risk for thromboembolic cerebrovascular events seen in AF patients, the question arises as to whether stroke and AF occurring with modified incidences in diabetic individuals under therapy with various classes of antihyperglycemic medications are interrelated and should be considered as a whole. At present, the medical literature lacks studies specifically designed to investigate a cause–effect relationship between the incidences of AF and stroke driven by different antidiabetic agents. In default of such proof, we reviewed the existing evidence correlating the major classes of glucose-controlling drugs with their associated risks for AF and stroke; however, supplementary proof is needed to explore a hypothetically causal relationship between these two, both of which display peculiar features in the setting of specific drug therapies for glycemic control.
Highlights
Cardiovascular disease (CVD) is the main cause of morbidity and mortality in type 2 diabetes patients
A subsequent meta-analysis of 27,705 diabetic patients from 17 trials found SUs to be associated with a higher relative risk for stroke than other antihyperglycemic drugs administered for glycemic control [20]
In a cohort study on 90,880 patients with type 2 diabetes previously treated with metformin as a first-line antihyperglycemic drug, the add-on of Dipeptidyl peptidase-4 (DPP-4) inhibitors as a second-line therapy was found to be associated with a lower risk of Atrial fibrillation (AF) development than the use of other drugs as the second antidiabetic medication [38]
Summary
Cardiovascular disease (CVD) is the main cause of morbidity and mortality in type 2 diabetes patients. In a turning point in diabetes-related clinical research, several older or newer drugs used to control glycemic values in diabetic patients were recently shown—mostly in observational studies, post-hoc analyses of the major trials, or various meta-analyses—to display different levels of risk for either AF or stroke [7,8]. Such evidence exists for all classes of antidiabetic drugs included in the major international guidelines [3,7,8]. The following sections summarize the data related to the risk of AF and stroke for each class of antihyperglycemic agents
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