Effect of Long-term Incretin-Based Therapies on Ischemic Heart Diseases in Patients with Type 2 Diabetes Mellitus: A Network Meta-analysis

Abstract

Patients with type 2 diabetes mellitus (T2DM) experience many cardiovascular complications. Several studies have demonstrated the cardioprotective effects of incretin-based therapies; however, there are few studies on the effects of long-term incretin-based therapies on cardiovascular events. Therefore, the present study conducted a systematic review and network meta-analysis to evaluate the effects of long-term incretin-based therapies on ischaemic diseases. We searched PubMed, CENTRAL, and Clinicaltrial.gov to retrieve randomised control trials reported until December 2016 and enrolled only RCTs with more than a 1-year follow-up. The network meta-analysis was performed using R Software with a GeMTC package. A total of 40 trials were included. Dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 agonists were associated with a lower risk of myocardial infarction (MI) than were sulfonylureas (odds ratio [95% credible interval] 0.41 [0.24–0.71] and 0.48 [0.27–0.91], respectively). These results suggested that patients with T2DM receiving long-term incretin-based therapies have a lower risk of MI than do those receiving sulfonylurea-based therapy. These findings highlight the risks of cardiovascular events in patients who receive long-term incretin-based therapies, and may provide evidence for the selection of antidiabetic therapy in the future.

Blood Sugar Regulation for Cardiovascular Health Promotion and Disease Prevention

“…Meta-analyses found that GLP-1 RA 1) reduced body weight, systolic BP, triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) better than insulin (57), 2) were associated with a lower risk of myocardial infarction after long-term treatment in comparison to sulfonylurea-based therapy (18), 3) reduced the risk of all-cause and CV mortality in comparison to placebo (58,59), 4) reduced the risk of severe hypoglycemia (58), and 5) did not increase the risk of heart failure, stroke, and microvascular complications including diabetic retinopathy (DR) and nephropathy (DN) (59). However, one GLP-1 RA, exenatide, was found to increase the risk of arrhythmias in T2DM patients (55).…”

“…Established mechanisms in cardiovascular health promotion entail developing strategies for screening and preventive interventions tackling the mechanisms of disease development (16). Although trials of intensive glucose reduction via medication in the past decades showed no significant macrovascular benefits (17), recent studies of glucose lowering using glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown sizable reductions in hard CVD endpoints compared to established glucose lowering strategies (18,19). This highlights the importance of the mechanisms tackled by these drugs in preventing CVD in DM patients.…”

Neutrophils Release Metalloproteinases during Adhesion in the Presence of Insulin, but Cathepsin G in the Presence of Glucagon

“…Metformin has a glucose-lowering effect, inhibiting hepatic gluconeogenesis and counteracting the action of glucagon [ 19 ]. GLP-1 receptor agonists, DPP-4 inhibitors, and metformin have beneficial effects on cardiovascular complications in patients with type 2 diabetes, as well as in patients with reperfusion after ischemia [ 20 – 22 ]. Prevention of vascular adhesion of monocytes contributes to the cardiovascular protective effect of GLP-1 analogs [ 23 , 24 ].…”

The role of dipeptidylpeptidase-4 inhibitors in management of cardiovascular disease in diabetes; focus on linagliptin

“…Most of the large trials investigating the CV safety profile of DPP-4 inhibitors (SAVOR-TIMI, TECOS, EXAMINE, and CARMELINA) were designed to compare the DPP-4 inhibitor to placebo; however the ongoing CAROLINA trial was designed to compare the CV effects of linagliptin to glimeperide as active comparator and will soon (second half of 2018) provide valuable information regarding the impact of DPP-4 inhibition in diabetic CV outcomes [ 27 , 31 , 32 ]. Lastly, a very recent systematic review and network meta-analysis, designed to evaluate the effects of long-term CV safety of DPP-4 inhibitors (and GLP-1 agonists), showed lower risk of MI compared to SU-based therapies when these drugs are administered for more than 1 year [ 33 ].…”

“…These salutary effects were not accompanied by improved cardiac function. Despite these mixed results in preclinical settings, it has been reported that DPP-4 inhibitors improve DD or long term survival in T2DM patients after acute myocardial infarction [ 28 , 33 , 81 ]. Moreover, this improvement occurred in both sexes showing CV protection regardless of sex [ 28 ].…”