Impact of Glucose-Lowering Medications on Cardiovascular and Metabolic Risk in Type 2 Diabetes

Abstract

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Among the well-known pathophysiologic factors, crucial roles are played by endothelial dysfunction (caused by oxidative stress and inflammation hyperglycemia-linked), increased activity of nuclear factor kB, altered macrophage polarization, and reduced synthesis of resident endothelial progenitor cells. As consequence, a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque is arguable, finally leading to significantly increased cardiovascular mortality. Main managements are focused on both prevention and early diagnosis, by targeted treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (e.g., Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, and DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial (dys)functions, inflammatory markers, biomarkers of both oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of the main trials focused on the cardiovascular safety of these drugs from the CV standpoint.

Novel Therapeutical Approaches to Managing Atherosclerotic Risk

“…Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RAs) may favorably affect CV risk through direct actions on the myocardium and blood vessels [ 61 ], and it has been shown that liraglutide may exert significant effects at the early stage of atherosclerosis and slows its progression [ 62 ]. GLP-1 RAs are used in diabetic patients but liraglutide is also approved for the treatment of obesity; interestingly, liraglutide has been shown to improve lipid and lipoprotein profile, and sdLDL, in a rigorous randomized, placebo-controlled, cross-over, double-blind study on patients with obesity, regardless the presence of diabetes [ 63 ].…”

Glycated Albumin for Glycemic Control in T2DM Population: A Multi-Dimensional Evaluation

“… 28 This would strengthen the consideration that GA is a useful marker for the monitoring activities of diabetes, thus being able to determine the effectiveness of treatment before initiating or changing medication for individuals with diabetes. 12 , 47 Indeed, there may be no discernible reduction in the HbA1c level until several weeks after starting treatment, which may delay the determination of whether the specific therapeutic regimen is effective. 28 …”

Recent Updates and Advances in the Use of Glycated Albumin for the Diagnosis and Monitoring of Diabetes and Renal, Cerebro- and Cardio-Metabolic Diseases

“…The GA test provides information on the mean blood glucose concentration in the last 15–20 days before blood collection [ 4 , 6 , 8 , 11 , 19 , 24 ].…”

“…GA, a unique post-translational product of the glycosylation of albumin, has been shown to be a useful biomarker in: (i) clinical conditions in which the dosage of glycated hemoglobin (HbA1c) does not reflect glycemic compensation, such as chronic renal failure, gestational diabetes, dialysis complications, hemorrhages, recent transfusions, hemolytic anemia and hemoglobin variants [ 6 , 9 , 10 , 11 , 12 , 13 ]; (ii) patients with poorly controlled diabetes and with postprandial hyperglycemia in order to monitor short-term glycemic fluctuation [ 14 , 15 ]; (iii) diabetic patients for monitoring therapeutic response [ 16 , 17 , 18 , 19 ]; (iv) detecting prediabetes even in the presence of normoglycemia, which is a priority because the effectiveness of this lifestyle intervention is lost if diabetes has already developed [ 20 , 21 ]. It is well known that fructosamine represents all the circulating glycated proteins, therefore Glycated Albumin is biochemically recognized as a form of fructosamine [ 14 ].…”