Effects of Dipeptidyl Peptidase 4 Inhibitors and Sodium-Glucose Linked coTransporter-2 Inhibitors on cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis

Meta-Analysis of Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiovascular Outcomes and All-Cause Mortality Among Patients With Type 2 Diabetes Mellitus

“…Our findings from pairwise and network meta-analyses showed that SGLT2 inhibitors were not associated with any increased risk of all-cause mortality and CV outcomes, and only empagliflozin showed a CV protective benefit, which was consistent with two meta-analyses 24,25 . The potential effect of glucose-lowering agents on CV events might depend on how their differing modes of action modulate CV risk factors 26 .…”

“…The conflicting results might be caused by the fact that more non-serious CV events were recorded in EMPA-REG OUTCOME trial, but only rare serious or fatal CV events were reported in most of the phase II and III RCTs, yielding low sample size/power to detect a statistical difference in these small RCTs, even in the meta-analysis. Therefore it is not surprising that there was no significant difference between the other two SGLT2 inhibitors (dapagliflozin and canagliflozin) and placebos in terms of MACE and all-cause mortality, which was consistent with three pairwise meta-analyses 2,24,27 . Two meta-analyses showed that the combined SGLT-2 inhibitor group (mainly dapagliflozin and canagliflozin) was not significantly associated with an reduced risk for MACE compared with placebo or active treatments 2 27 , and one meta-analysis indicated that canagliflozin and dapagliflozin did not significantly affect mortality or CV outcomes 24 .…”

“…Therefore it is not surprising that there was no significant difference between the other two SGLT2 inhibitors (dapagliflozin and canagliflozin) and placebos in terms of MACE and all-cause mortality, which was consistent with three pairwise meta-analyses 2,24,27 . Two meta-analyses showed that the combined SGLT-2 inhibitor group (mainly dapagliflozin and canagliflozin) was not significantly associated with an reduced risk for MACE compared with placebo or active treatments 2 27 , and one meta-analysis indicated that canagliflozin and dapagliflozin did not significantly affect mortality or CV outcomes 24 . However, one meta-analysis found a lower risk of MACE from dapagliflozin than control 25 .…”

The year in cardiology 2017: heart failure

“…But in EMPA-REG (10% HF at baseline), empagliflozin reduced HF hospitalization by 35%, 60 and in CANVAS (14% HF at baseline), canagliflozin reduced HF hospitalization by 33%. 61 This has generated considerable interest in SGLT2 and also SGLT2/1 inhibition in HF 62,63 and several trial programs are underway 64 to address whether SGLT2/1 inhibitors in combination with diuretics can improve outcomes in prevalent HF, with HFrEF, HFmrEF, and/or HFpEF, and with and without diabetes. Recent real-world data suggest that AF is more common in HF than previously believed, at 53% in HFrEF, 60% in HFmrEF and 63% in HFpEF in one generalizable study.…”

A new era in the management of type 2 diabetes: Is cardioprotection at long last a reality?

“…The active form, GLP-1(7-36), which is rapidly degraded by the enzyme DPP-IV, binds GLP-1 receptor, which is expressed not only in pancreatic islet cells, but also in the kidney, lung, brain, gastrointestinal tract and heart. Research has manipulated the biology of the entero-insular axis producing both injectable GLP-1 agonists that are used as an exogenous source of GLP-1 and oral DPP-4 inhibitors that shield the endogenous peptide from degradation [3]. Findings from our laboratory demonstrated for the first time that the administration of either GLP-1 native peptide or the DPP-4 inhibitor protects against myocardial IRI in the isolated rat heart model through a mechanism not driven by the stimulation of insulin secretion, but by the activation of intracellular prosurvival kinases cascades [4].…”