GLP-1 Receptor Agonists for the Reduction of Atherosclerotic Cardiovascular Risk in Patients With Type 2 Diabetes

Abstract

Patients with type 2 diabetes are at high risk for development of cardiovascular disease, including myocardial infarction, stroke, heart failure, and cardiovascular death. Multiple large cardiovascular outcome trials with novel glucose-lowering agents, namely SGLT2i (SGLT2 inhibitors) and GLP-1 RA (GLP-1 receptor agonists), have demonstrated robust and significant reductions of major adverse cardiovascular events and additional cardiovascular outcomes, such as hospitalizations for heart failure. This evidence has changed the landscape for treatment of patients with type 2 diabetes. Both diabetes and cardiology guidelines and professional societies have responded to this paradigm shift by including strong recommendations to use SGLT2i and/or GLP-1 RA, with evidence-based benefits to reduce cardiovascular risk in high-risk individuals with type 2 diabetes, independent of the need for additional glucose control. GLP-1 RA were initially developed as glucose-lowering drugs because activation of the GLP-1 receptor by these agents leads to a reduction in blood glucose and an improvement in postprandial glucose metabolism. By stimulating GLP-1R in hypothalamic neurons, GLP-1 RA additionally induce satiety and lead to weight loss. Data from cardiovascular outcome trials demonstrated a robust and consistent reduction in atherothrombotic events, particularly in patients with established atherosclerotic cardiovascular disease. Despite the consistent evidence of atherosclerotic cardiovascular disease benefit from these trials, the number of patients receiving these drugs remains low. This overview summarizes the experimental and clinical evidence of cardiovascular risk reduction offered by GLP-1 RA, and provides practical information on how these drugs should be implemented in the treatment of type 2 diabetes in the cardiology community.

Adaptive infusion of a glucagon‐like peptide‐1/glucagon receptor co‐agonist G3215, in adults with overweight or obesity: Results from a phase 1 randomized clinical trial

“…As seen with other GLP‐1 receptor agonists, 36 G3215 led to a sustained reduction in systolic blood pressure during the infusion period. However, a sustained chronotropic effect of G3215 was not observed, in contrast to reports with semaglutide treatment 37,38 and the GLP‐1R/GCGR co‐agonist NN1177 19 .…”

Compare SGLT2I versus non-SGLT2I users in type-2 diabetic mellitus patients on GLP-1 receptor agonist: A population-based and machine learning causal inference analysis

“…Nevertheless, evidence suggests SGLT2I was not significantly associated with a lower risk of acute coronary artery syndrome compared to non-SGLT2I users amongst elderly T2DM patients [26] and patients with renal failure [27]. These differences could be explained by the baseline atherosclerotic profile and the cardiorenal status; in this study, GLP1a alone, with or without interacting with SGLT2I, might have already improved those factors [28, 29].…”

Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association

“…31,32 Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) not only improve insulin resistance and glycemia but also reduce weight and cause significant reductions in CVD mortality. 33 Reninangiotensin-aldosterone system (RAAS) inhibitors also have important cardiovascular and kidney benefits. [34][35][36] The availability of effective approaches to address excess adiposity and related insulin resistance provides the opportunity to address the root cause of a large component of CKM syndrome.…”