The Impact of Novel Anti-Diabetic Medications on CV Outcomes: A New Therapeutic Horizon for Diabetic and Non-Diabetic Cardiac Patients

Abstract

It is estimated that in the past two decades the number of patients diagnosed with diabetes mellites (DM) has doubled. Despite significant progress in the treatment of cardiovascular disease (CVD), including novel anti-platelet agents, effective lipid-lowering medications, and advanced revascularization techniques, patients with DM still are least twice as likely to die of cardiovascular causes compared with their non-diabetic counterparts, and current guidelines define patients with DM at the highest risk for atherosclerotic cardiovascular disease and major adverse cardiovascular events (MACE). Over the last few years, there has been a breakthrough in anti-diabetic therapeutics, as two novel anti-diabetic classes have demonstrated cardiovascular benefit with consistently reduced MACE, and for some agents, also improvement in heart failure status as well as reduced cardiovascular and all-cause mortality. These include the sodium-glucose cotransporter-2 inhibitors and the glucagon-like peptide-1 receptor agonists. The benefits of these medications are thought to be derived not only from their anti-diabetic effect but also from additional mechanisms. The purpose of this review is to provide the everyday clinician a detailed review of the various agents within each class with regard to their specific characteristics and the effects on MACE and cardiovascular outcomes.

Autophagy and mitophagy as potential therapeutic targets in diabetic heart condition: Harnessing the power of nanotheranostics

“…The emerging patterns in diabetes therapies and supervision have unveiled the imperative need for scrupulous research aimed at testing composites and their counterparts in clinical trials ( Table 2 ). The conventional intervention orthodoxy is challenged via clinical trials using novel anti-diabetic drug classes that show cardiovascular benefits despite very minor glucose lowering and point to the mechanism of action associated with a particular molecular pathway targeting autophagy as a key factor in outcomes [ 145 ].…”

Sodium-Glucose Co-Transporter 2 Inhibitors as a Powerful Cardioprotective and Renoprotective Tool: Overview of Clinical Trials and Mechanisms

“…To highlight, valid conclusions can be drawn from studies solely on the basis of primary outcomes (e.g., MACE here), while this should not be done on the basis of secondary outcomes (which are exclusively affirmative) due to insufficient statistical strength. In addition to the primary MACE outcomes, this paragraph will also present isolated secondary renal outcomes and outcomes for heart failure (HF) of some conducted CVOTs purely because they have hinted towards the renoprotective effects of SGLT2i and beneficial effects on chronic heart failure and thus set the need to conduct further targeted trials primarily designed to demonstrate the effectiveness of some representatives in these indications [11][12][13].…”

A Critical View over the Newest Antidiabetic Molecules in Light of Efficacy—A Systematic Review and Meta-Analysis

“…The novel antidiabetic non-insulin drugs are represented by dipeptidyl peptidase-4 inhibitor (DPP-4i), sodium glucose-2 transporter inhibitors (SGLT-2i), glucagon-like peptide one receptor agonists (GLP-1 Ra), and a dual glucose-dependent insulinotropic polypeptide-GLP-1 receptor agonist that is represented by tirzepatide. Their benefits are secondary to their pleiotropic effects, which exceed only an improvement in the glycemic control, reflected by an improved level of A1C hemoglobin or blood glucose, respectively, due to a reduction in the patient's body weight, improvement of the lipidic profile, blood pressure (BP) both systolic and diastolic, along with pleiotropic effects, such as a decreased marker of inflammation [28][29][30]. Because T2DM is included in the cardio-renal metabolic syndrome, it is also important to emphasize the benefits of the novel antidiabetic non-insulin drugs from the large cardiovascular outcome trials (CVOT); specifically, a reduction in the major adverse cardiovascular events (MACE), including acute MI, stroke, CV mortality, all-cause mortality, and CV safety [28][29][30].…”