Cardiovascular effects of anti-diabetes drugs

Abstract

Introduction Cardiovascular disease remains the major contributor to morbidity and mortality in diabetes. From the need to reduce cardiovascular risk in diabetes and to ensure that such risk is not exacerbated by drug treatments, governmental regulators and drug manufacturers have focused on clinical trials evaluating cardiovascular outcomes. Areas covered Findings from mechanistic and clinical trials of biguanides, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose transporter 2 (SGLT-2) inhibitors will be reviewed. These drug classes will be compared within the context of available cardiovascular outcomes data. Clinical implications of new study regulations will be examined. Expert opinion Recent cardiovascular studies provide a more comprehensive evaluation of specific anti-diabetes therapy in individuals with high cardiovascular risk. Long-term effects of anti-hyperglycemic agents in patients with lower cardiovascular risk are still speculative. Historical data supports continued use of metformin as a first-line agent. DPP-4 inhibitors and GLP-1 receptor agonists appear to have neutral effects on cardiovascular outcomes. The significantly decreased cardiovascular risk associated with empagliflozin SGLT-2 inhibitor therapy is impressive and may change how practitioners prescribe add-on therapy to metformin.

Phlorizin Exerts Direct Protective Effects on Palmitic Acid (PA)-Induced Endothelial Dysfunction by Activating the PI3K/AKT/eNOS Signaling Pathway and Increasing the Levels of Nitric Oxide (NO)

“…A growing number of studies have illustrated that SGLT2 inhibitors reduce the CV risk factors in T2DM and demonstrated that the function of attenuating cardiovascular dysfunction was not a significant contributor to the metabolic effects [ 11 , 24 , 25 ]. Ipragliflozin improved hyperglycemia, ameliorated the impaired p-AKT and p-eNOS, and prevented the development of endothelial dysfunction in STZ-induced diabetes mice, at least partially by attenuation of oxidative stress [ 26 ].…”

“…Many studies have convincingly shown that SGLT2 inhibitors not only lower the A1C levels in diabetic individuals with an overall improvement in cardiovascular function, but also induce the development of renal and peripheral insulin sensitivity and β cell function, which means that the presence of SGLT2 inhibitors is of functional significance [ 10 ]. More importantly, studies have shown a beneficial decline in several other CV risk factors, cardiovascular morbidity, and mortality, and even all-cause death by using of SGLT2 inhibitors [ 11 ].…”

Heart failure outcomes in patients with type 2 diabetes mellitus: findings from the cardiovascular outcome trials of antidiabetes agents

“…Although several studies have proposed the underlying mechanisms for the cardio-protective activity of various antidiabetes drug classes, there still exists few lacunae [4]. Improved CV outcomes with metformin were reported in patients with T2DM, which could be due to the improved endothelium-independent blood flow and enhancement of nitric oxide dependent or independent vasodilation [26]. The cardiac protective effects of the GLP-1 agonists is due to their renal protection, reduction in ischaemic injury, chronic inflammation and ectopic fat deposition [27,28].…”

A Roadmap on the Prevention of Cardiovascular Disease Among People Living With Diabetes

“…This is supported by 77% of survey respondents in the second survey round. Yet first-line treatment approaches have traditionally relied on the evidence of therapeutic strategies for the control of hyperglycemia [69], with little understanding on the effects of these treatments on cardiovascular risk [70].…”