Table 2 Summary of the drugs that are used to manage IR and their role in AF patients
Class or agent | Brief effect on AF patients | Mechanism of action in AF patients |
|---|---|---|
Metformin | The significant reduction in the risk of recurrent atrial arrhythmias was independently linked to the treatment with metformin after catheter ablation (CA) for AF in patients with diabetes mellitus patients. Whether this effect is due to pleiotropic effects or glycemic control on electro anatomical mechanisms of atrial fibrillation remains to be determined [85] In diabetic patients without and with myocardial infarction, the decreased incidence of AF was linked due to metformin and also prevent the structural and electrical remodeling of the left atrium [39] The lower risk of hospitalization for atrial fibrillation is linked to the use of metformin in patients with type 2 diabetes mellitus [49] | Exerts an insulin-sensitizing effect [42] Might have anticancer, anti-inflammatory and antimicrobial and antiaging effects [43,44,45,46] The expression of insulin receptors was increased [51] Tyrosine kinase was activated, Increases ketone body metabolism, Fatty acid oxidation is promoted, Lipid accumulation was reduced, In cardiomyocytes—the expression of glucose transporter is induced, all happened due to the activation of 5’- adenosine monophosphate-activated protein kinase [40, 41] The facilitated more efficient energy use with reduction of metabolic stress [40, 41] Signaling pathways of transforming growth factor-beta one were inhibited, reducing the metabolic stress and IR, Inflammation also inhibited and alleviated cardiac fibrosis [54] Improving the dysfunction of epicardial adipose tissue [52] |
Thiazolidinediones (TZDs) | Pooled analysis of the various studies had revealed that approximately 30% risk of developing AF patients were lowered with the treatment of TZDs as compared to control [odds ratio (OR): 0.73, 95% confidence interval (CI): 0.62 to 0.87, p = 0.0003] [62] Reduced risk of developing AF was linked with the use of thiazolidinedione to treat diabetes as compared with other antidiabetic drugs as second-line treatment [61] The use of biguanides or thiazolidinediones may be associated with a low risk of new-onset atrial fibrillation (NAF) as compared with non-user (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.71–0.95 and OR 0.72, 95% CI 0.63–0.83, respectively) [48] The authors did not find a significant reduction of AF incidence with the use of thiazolidinediones [86] | Activation of peroxisome proliferator-activation receptor by the insulin sensitizers, Improves insulin action, Decrease insulin resistance [55] Decrease the elevated free fatty acid levels present in insulin-resistant patients, improves glycemic control, improves many of the abnormalities which are part of the insulin resistance syndrome [55] Insulin sensitizer that also has anti-inflammatory effects [61] |
Sodium-glucose cotransporter-2 (SGLT2) inhibitors | The individual who received an SGLT2 inhibitor had 0.9% of the incidence of AF as compared to 1.1% in those who received a placebo Pooled results showed a significantly lower incidence of AF in individuals with and without diabetes (relative risk 0.79, 95% confidence interval 0.67,0.93) [87] Sodium-glucose transporter 2 inhibitors (SGLT2i) use is associated with 19.33% lower serious adverse events (SAEs) of AF/atrial flutter (AFL) compared with the placebo [88] AF was reported disproportionally less frequently among patients using SGLT2i than among patients using other glucose-lowering medications [89] SGLT2i therapy was associated with a significant reduction in the risk of incident atrial arrhythmias (odds ratio 0.81; 95% confidence interval 0.69–0.95; p = .008) and sudden cardiac death (SCD) in patients with T2DM as compared to control [90] | To reduce the risk of major adverse CVDs and hospitalization for heart failure [67] |
Glucagon-like peptide 1 (GLP-1) receptor Agonist’s | GLP1-RA did not increase the risk of AF [65] The incidence of NAF was not associated with GLP-1 [72] | Used for glucose-lowering [69] Reduction of inflammation, lipid concentration and systolic blood pressure, a significant reduction in body weight [70] Lower risk of major adverse cardiovascular events [67] |
Dipeptidyl peptidase-4 (DPP-4) Inhibitor’s | The second line of diabetes therapy uses DPP-4 inhibitors that are linked to a lower risk of AF as compared to the use of other antidiabetic drugs [76] Other studies demonstrate that both dipeptidyl peptidase 4 inhibitor and metformin decrease the risk of AF with diabetes [76, 77] DDP-4 inhibitors could have an antiarrhythmic effect in the prevention and management of AF [62] | Cardioprotective effects [74] Inactivates some cytokines, chemokines, neuropeptides that are involved in inflammation, vascular function, and immunity [74] Could shorten the duration of AF [79] |
Sulfonylurea’s | Authors revealed that the increased risk of new-onset AF was not related to Sulfonylurea [48] | ATP-sensitive potassium (KATP) channel is the main principle target that played role in controlling the beta-cell membrane potential [80] |