The mediators that were identified support existing and novel hypothesized mechanisms for the prevention of heart failure with sodium glucose cotransporter 2 inhibitors.
The most impressive finding has been the substantial and consistent risk reduction in HF hospitalization seen across 4 trials of sodium glucose cotransporter 2 inhibitors.
Based on such evidence, the recent guidelines for the management of type 2 diabetes now suggest that SGLT-2 inhibitors should be preferred among oral agents in combination with metformin, in patients at increased cardiovascular risk, chronic kidney disease or heart failure.
Whilst the lack of benefits on MACE may seem in contrast with the results of previous SGLT-2 inhibitors cardiovascular outcome trials, DECLARE clearly delineates the real cardiovascular effects of SGLT-2 inhibitors, which mainly tackle heart failure.
In the Horizon membership, we confirmed that SGLT-2 inhibitors reduce HF hospitalizations, resulting in reduced medical spending and savings in total cost of care.
We particularly favour SGLT2 inhibitors in those where additional weight loss and blood pressure reductions are desired, and in patients with heart failure or cardiovascular disease.
Based on the available evidence, we conclude that SGLT-2 inhibitors represent an evidence-based therapeutic option for the primary prevention of heart failure hospitalization and secondary prevention of CVD in patients with T2DM, and should be considered early on in the treatment algorithm for patients with multiple risk factors, or those with established CVD.
A recent cardiovascular (CV) safety trial, the EMPA-REG OUTCOME trial, showed that empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, markedly reduced CV death and all-cause mortality and hospitalization for heart failure in patients with T2DM and established CV disease (CVD).
In recent trials, sodium-glucose co-transporter-2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have both shown a significant reduction in HF hospitalization in patients with established CV disease or at risk of CV disease.
There were no differences in the risk ratios between men and women, SGLT2 versus control (placebo), for vascular efficacy outcomes or death (all P for interaction ≥.12), with clear protection shown against major adverse cardiovascular events, heart failure, vascular death and total mortality.
The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes.
The SGLT2 inhibitor empagliflozin was shown to reduce HF admissions and cardiovascular mortality in patients with prior cardiovascular disease including HF.
The sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin has been shown to reduce major cardiovascular events in type 2 diabetic patients, with a pronounced decrease in hospitalization for heart failure (HF) especially in those with HF at baseline.
These effects may contribute to the protective effects of SGLT2 inhibitors on blood pressure and heart failure observed in diabetic patients with chronic kidney diseases.
This review explores the effects of pharmacologic SGLT2 inhibitors' use in cardiac function and discusses the potential role of this class of medication as a treatment for HF.
The first CV outcome study terminated with empagliflozin, a specific SGLT2 inhibitor, has shown a reduction in CV mortality and in heart failure hospitalization, suggesting a beneficial impact on cardiac function which remains to be demonstrated.
Amongst those with type 2 diabetes mellitus who did not have established cardiovascular disease but did present with multiple risk factors, SGLT2 inhibitors lowered the combined endpoint of cardiovascular death or hospitalization for heart failure but had little impact on the occurrence of major adverse cardiac events.
Furthermore, novel drugs that have received interest in HF include angiotensin receptor blocker-neprilysin inhibitor (ARNi) and sodium glucose cotransporter 2 (SGLT-2) inhibitors, whose favorable cardiovascular profile has been at least partly attributed to their effects on metabolism.