BACKGROUND Dipeptidyl peptidase-4 (DPP-4) inhibitors are a generally safe and well tolerated antidiabetic drug class with proven efficacy in type 2 diabetes mellitus (T2DM). Recently, a series of large, randomized controlled trials (RCTs) addressing cardiovascular outcomes with DPP-4 inhibitors have been published. AIM To pool data from the aforementioned trials concerning the impact of DPP-4 inhibitors on surrogate cardiovascular efficacy outcomes and on major cardiac arrhythmias. METHODS We searched PubMed and grey literature sources for all published RCTs assessing cardiovascular outcomes with DPP-4 inhibitors compared to placebo until October 2020. We extracted data concerning the following “hard” efficacy outcomes: fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization and cardiovascular death. We also extracted data regarding the risk for major cardiac arrhythmias, such as atrial fibrillation, atrial flutter, ventricular fibrillation and ventricular tachycardia. RESULTS We pooled data from 6 trials in a total of 52520 patients with T2DM assigned either to DPP-4 inhibitor or placebo. DPP-4 inhibitors compared to placebo led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction [risk ratio (RR) = 1.02, 95%CI: 0.94-1.11, I 2 = 0%], hospitalization for heart failure (RR = 1.09, 95%CI: 0.92-1.29, I 2 = 65%) and cardiovascular death (RR = 1.02, 95%CI: 0.93-1.11, I 2 = 0%). DPP-4 inhibitors resulted in a non-significant decrease in the risk for fatal and non-fatal stroke (RR = 0.96, 95%CI: 0.85-1.08, I 2 = 0%) and coronary revascularization (RR = 0.99, 95%CI: 0.90-1.09, I 2 = 0%), Finally, DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina (RR = 1.00, 95%CI: 0.85-1.18, I 2 = 0%). As far as cardiac arrhythmias are concerned, DPP-4 inhibitors did not significantly affect the risk for atrial fibrillation (RR = 0.95, 95%CI: 0.78-1.17, I 2 = 0%), while they were associated with a significant increase in the risk for atrial flutter, equal to 52% (RR = 1.52, 95%CI: 1.03-2.24, I 2 = 0%). DPP-4 inhibitors did not have a significant impact on the risk for any of the rest assessed cardiac arrhythmias. CONCLUSION DPP-4 inhibitors do not seem to confer any significant cardiovascular benefit for patients with T2DM, while they do not seem to be associated with a significant risk for any major cardiac arrhythmias, except for atrial flutter. Therefore, th...

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Objective: Patients with type 2 diabetes mellitus (T2DM) experience a significantly increased risk for atrial fibrillation (AF) compared to unaffected subjects. The latter confers to increased risk for heart failure, all-cause and cardiovascular mortality. Notably, even patients with sufficient glycemic control feature an increased risk for AF. Thus, it seems to be of interest whether antidiabetic treatment can affect the risk for AF among patients with T2DM. Design and method: We searched PubMed from its inception to 2 October 2020. We sought to determine the risk of AF with the use of newer antidiabetics, namely dipeptidyl-peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, extracting corresponding data from the published cardiovascular and renal outcome trials. We assessed the risk for AF with each drug class separately. Results: We pooled data from 4 trials with DPP-4 inhibitors versus placebo or active comparator in a total of 34,884 patients, from 7 trials with GLP-1RAs versus placebo in a total of 55,943 patients and from 7 trials with SGLT-2 inhibitors versus placebo in a total of 55,966 patients. Risk of bias is considered as low across all selected studies. DPP-4 inhibitor treatment resulted in a non-significant decrease in the risk for AF, equal to 7% (RR = 0.93, 95% CI; 0.75 to 1.16, I2 = 1%). Similarly, GLP-1RA treatment produced a non-significant decrease in the risk for AF, equal to 12% (RR = 0.88, 95% CI; 0.76 to 1.03, I2 = 29%). Notably, SGLT-2 inhibitor treatment significantly decreased the risk for AF 19% (RR = 0.81, 95% CI; 0.69 to 0.95, I2 = 0%). Conclusions: Collectively, newer antidiabetics do not confer an increased risk for AF among patients with T2DM, while, SGLT-2 inhibitors seem to be protective, providing an additional cardiovascular benefit, besides the well-established ones.

Objective Hypertension augments overall cardiovascular risk in patients with type 2 diabetes mellitus (T2DM); however, control rates remain suboptimal. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have revolutionized the field of T2DM therapeutic management due to their multiple pleiotropic effects. Therefore, we sought to determine the effect of this class on ambulatory blood pressure monitoring (ABPM), pooling data from relevant randomized controlled trials (RCTs). Methods We searched major electronic databases, namely PubMed and Cochrane Library, along with gray literature sources, for RCTs assessing the effect of various GLP-1RAs on ambulatory BP in patients with T2DM. Results We pooled data from seven RCTs in total. GLP-1RA treatment compared to placebo or active control resulted in a nonsignificant decrease in 24-h SBP (mean difference = −1.57 mm Hg; 95% CI,−4.12 to 0.98; I 2 = 63%) and in 24-h DBP (mean difference = 1.28 mmHg; 95% CI,−0.31 to 2.87; I 2 = 49%). No subgroup differences between the various GLP-1RAs were detected. Conclusion GLP-1RAs treatment does not influence either systolic or diastolic ambulatory BP in patients with T2DM.

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