In primary prevention, SGLT-2i reduce both the risk of hospitalization for HF and progression of DKD; in secondary prevention, SGLT-2i are effective on the three endpoints, DPP-4i are neutral, while GLP1-RA show mixed results.
The benefits with GLP-1 RAs are most likely derived through the reduction of atherosclerosis-related events while SGLT-2is seem mostly to reduce heart failure-related events.
Such CVOTs have demonstrated that the effects of the new antidiabetic drugs on the mutual interactions between T2DM and HF may develop across different phases:Results of such trials can be summarized as: (a) all different classes of novel glucose-lowering drugs have good cardiovascular safety profile; (b) with respect to HF, DPP4 inhibitors might tend to increase risk; (c) sodium-glucose co-transporter 2 inhibitors (SGTLi), significantly reduce it; (d) glucagon-like peptide 1 receptor agonists (GLP1) tend to be neutral.
In comparison, GLP-1 RA appear to preferentially reduce ischemic events (stroke or myocardial infarction) over hospitalization for heart failure, and demonstrated renoprotection in several of the CVOTs.
SGLT-2 inhibitors and GLP-1 RAs significantly reduced MACE (OR 0.88, 95% CI 0.82-0.95 and OR 0.87, 95% CI 0.82-0.93), hospitalisation for HF (OR 0.68, 95% CI 0.61-0.77 and OR 0.87, 95% CI 0.82-0.93), and renal composite outcome (OR 0.59, 95% CI 0.52-0.67 and OR 0.86, 95% CI 0.78-0.94) compared to placebo, but SGLT-2 inhibitors reduced hospitalisation for HF (OR 0.79, 95% CI 0.69-0.90) and renal composite outcome (OR 0.69, 95% CI 0.59-0.80) more than GLP-1 RAs.
Five completed CVOTs with the GLP-1 RAs lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), exenatide once weekly (EXSCEL) and albiglutide (HARMONY) also failed to reveal any significant effect on HF risk.
Glucagon-like peptide (GLP-1) is a naturally occurring incretin used as a promising therapeutic agent in the treatment of acute myocardial infarction, dilated cardiomyopathy, and advanced heart failure.
SGLT2i reduced hospitalization for heart failure by 31% (HR, 0.69; 95% CI, 0.61-0.79; P<0.001), whereas GLP1-RA did not have a significant effect (HR, 0.93; 95% CI, 0.83-1.04; P=0.20).
Current evidence suggests that SGLT-2 inhibitors are more effective than either GLP-1 agonists or DPP-4 inhibitors for reducing the risk of hospitalization for HF in type 2 diabetes mellitus.
Consequently, GLP-1 RA drugs in addition to conventional hypoglycemic therapy may reduce hospital admissions for heart failure worsening, by increasing CRTd responders rate.Trial registration NCT03282136.
GLP-1 RA actions not only translate on an improvement of well-known cardiovascular risk factors such as glycaemic control, dyslipidaemia, weight, or arterial hypertension but also might show benefits on endothelial function, coronary ischaemia, and heart failure.
Prior studies with DPP-IV inhibitors, thiazolidinediones (TZDs), and GLP-1 agonists have demonstrated either a neutral effect on HF or increased HF hospitalizations.
Disturbances in calcium cycling are characteristic of heart failure (HF); therefore, the aim of this study was to investigate the effect of exendin-4 (a GLP-1 mimetic) on the regulation of calcium handling and to identify the underlying mechanisms in an HF rat model after myocardial infarction (MI).
Findings from recently completed trials indicate that a GLP-1 RA-induced increase in HR, regardless of magnitude, does not present an increased cardiovascular risk for subjects with T2DM, although a pronounced increase in HR may be associated with adverse clinical outcomes in those with advanced heart failure.
After matching each GLP-1 analog user to a sulfonylurea user on the time-conditional propensity scores from prescription-based exposure sets, the hazard ratio of heart failure with GLP-1 use was 0.73 (95%CI: 0.57-0.93).
The GLP-1 agonist liraglutide was recently shown to reduce cardiovascular and all-cause mortality, yet hospitalization for HF was not significantly reduced.