Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are an important asset in the armamentarium for the treatment of type 2 diabetes mellitus (type 2 DM). Incretin failure is a critical etiopathogenetic feature of type 2 DM, which, if reversed, results in improved glycaemic control. GLP-1 RAs are injectable peptides that resemble the structure and function of endogenous incretin GLP-1, but as they are not deactivated by the dipeptidyl peptidase-4 (DPP-4), their half-life is prolonged compared with native GLP-1. Based on their ability to activate GLP-1 receptor, GLP-1 RAs are classified as short-acting (exenatide twice-daily and lixisenatide once-daily), and long-acting (liraglutide once-daily and the once-weekly formulations of exenatide extended-release, dulaglutide, and albiglutide). Semaglutide, another long-acting, once-weekly GLP-1 RA, was recently approved by the FDA and EMA. Although all of these agents potently reduce haemoglobin A1C (HbA1c), there are unique features and fundamental differences among them related to fasting and postprandial hyperglycaemia reduction, weight loss potency, cardiovascular protection efficacy, and adverse events profile. It is imperative that current evidence be integrated and applied in the context of an individualised patient-centred approach. This should include not only glucose management but also targeting as many as possible of the pathophysiologic mechanisms responsible for type 2 DM development and progression.

Aims  Sudden cardiac death (SCD) and ventricular arrhythmias (VAs) are important causes of mortality in patients with type 2 diabetes mellitus (T2DM), heart failure (HF), or chronic kidney disease (CKD). We evaluated the effect of sodium–glucose cotransporter-2 (SGLT2) inhibitors on SCD and VAs in these patients. Methods and results  We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that enrolled patients with T2DM and/or HF and/or CKD comparing SGLT2i and placebo or active control. PubMed and ClinicalTrials.gov were systematically searched until November 2020. A total of 19 RCTs with 55 ,590 participants were included. Sudden cardiac death events were reported in 9 RCTs (48 patients receiving SGLT2i and 57 placebo subjects). There was no significant association between SGLT2i therapy and SCD [risk ratio (RR) 0.74, 95% confidence interval (CI) 0.50–1.08; P = 0.12]. Ventricular arrhythmias were reported in 17 RCTs (126 patients receiving SGLT2i and 134 controls). SGLT2i therapy was not associated with a lower risk of VAs (RR 0.84, 95% CI 0.66–1.06; P = 0.14). Besides the subgroup of low-dosage SGLT2i therapy that demonstrated decreased VAs compared to control (RR 0.45, 95% CI 0.25–0.82; P = 0.009), or to placebo (RR 0.46, 95% CI 0.25–0.85; P = 0.01), further subgroup analysis did not demonstrate any significant differences. Conclusion  SGLT2i therapy was not associated with an overall lower risk of SCD or VAs in patients with T2DM and/or HF and/or CKD. However, further research is needed since the number of SCD and VA events were relatively few leading to wide confidence intervals, and the point estimates suggested potential benefits.

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Atrial fibrillation (AF) and atrial flutter (AFL) are associated with adverse outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We investigated the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the incidence of AF and/or AFL in HFrEF patients. PubMed and ClinicalTrials.gov were systematically searched until March 2022 for randomized controlled trials (RCTs) that enrolled patients with HFrEF. A total of six RCTs with 9467 patients were included (N = 4731 in the SGLT2i arms; N = 4736 in the placebo arms). Compared to placebo, SGLT2i treatment was associated with a significant reduction in the risk of AF [relative risk (RR) 0.62, 95% confidence interval CI 0.44–0.86; P = 0.005] and AF/AFL (RR 0.64, 95% CI 0.47–0.87; P = 0.004). Subgroup analysis showed that empagliflozin use resulted in a significant reduction in the risk of AF (RR 0.55, 95% CI 0.34–0.89; P = 0.01) and AF/AFL (RR 0.50, 95% CI 0.32–0.77; P = 0.002). By contrast, dapagliflozin use was not associated with a significant reduction in the risk of AF (RR 0.69, 95% CI 0.43–1.11; P = 0.12) or AF/AFL (RR 0.82, 95% CI 0.53–1.27; P = 0.38). Additionally, a “shorter” duration (< 1.5 years) of treatment with SGLT2i remained associated with a reduction in the risk of AF (< 1.5 years; RR 0.58, 95% CI 0.36–0.91; P = 0.02) and AF/AFL (< 1.5 years; RR 0.52, 95% CI 0.34–0.80; P = 0.003). In conclusion, SGLT2i therapy was associated with a significant reduction in the risk of AF and AF/AFL in patients with HFrEF. These results reinforce the value of using SGLT2i in this setting.

Patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) may demonstrate distal microvascular embolization of thrombotic materials. We retrospectively examined 20 cases displaying extensive thrombus in the infarct-related artery (IRA), treated either with a two-step procedure, with interim tirofiban infusion, or immediate stent implantation. Distal embolization tended to be more common in the latter strategy, but, overall, the outcome was comparable. Thus, a two-staged procedure may be considered in selected cases of primary PCI associated with high thrombus burden.

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