The New Era for Reno-Cardiovascular Treatment in Type 2 Diabetes

Abstract

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease in the developed world. Until 2016, the only treatment that was clearly demonstrated to delay the DKD was the renin-angiotensin system blockade, either by angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. However, this strategy only partially covered the DKD progression. Thus, new strategies for reno-cardiovascular protection in type 2 diabetic patients are urgently needed. In the last few years, hypoglycaemic drugs, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, demonstrated a cardioprotective effect, mainly in terms of decreasing hospitalization for heart failure and cardiovascular death in type 2 diabetic patients. In addition, these drugs also demonstrated a clear renoprotective effect by delaying DKD progression and decreasing albuminuria. Another hypoglycaemic drug class, dipeptidyl peptidase 4 inhibitors, has been approved for its use in patients with advanced chronic kidney disease, avoiding, in part, the need for insulinization in this group of DKD patients. Studies in diabetic and non-diabetic experimental models suggest that these drugs may exert their reno-cardiovascular protective effect by glucose and non-glucose dependent mechanisms. This review focuses on newly demonstrated strategies that have shown reno-cardiovascular benefits in type 2 diabetes and that may change diabetes management algorithms.

Exploring Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors for Organ Protection in COVID-19

“…However, the dissociation of the curves for the outcomes that displayed the larger differences between groups in these trials (HHF and cardiovascular death) were observed during the first weeks suggesting that hemodynamic mechanisms, including mild natriuresis and reductions in blood pressure, may play a more prominent role [ 81 ]. Similarly, anti-inflammatory and antifibrotic effects and reversal of renal hypoxia of these agents could help towards a renoprotective action [ 94 , 95 , 96 ], but modulation of renal microcirculation is the most possible renoprotective mechanism [ 81 ]. Briefly, DM promotes renal injury through afferent arteriole vasodilation resulting in increased intraglomerular pressure and albuminuria.…”

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

“…On the basis of the well-known plethora of biological substrates of the enzyme DDP-4, its crucial enzymatic inhibition could lead to several bio-molecular effects, ranging from metabolic (improving glycaemic control, total cholesterol and triglyceride levels, and weight neutrality) to cardiovascular (reducing risk factors, ameliorating cardiac function and vascular repair) general improvements [1,9,10,62].…”

“…Cardiovascular disease (CVD) is the predominant cause of death in diabetic patients [1,2]. Hyperglycaemic status activates multiple maladaptive signalling pathways involving endothelial dysfunction, which leads to the emergence and rapid progression of the atherosclerotic disease with distinct characteristics.…”

“…The main therapy that attenuating DKD was the renin-angiotensin system blockade through angiotensin-converting enzyme inhibitors (ACEi) or Angiotensin II Receptor Blocker (ARB) treatments. Currently, it has been suggested as second-line therapy in T2DM patients the use of sodium-glucose transport protein 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) for their reno-cardiovascular safety profile [1]. Although they have shown a reassuring safety profile, unfortunately, the current guidelines do not fully allow us to identify the most appropriate drug according to a specific patient phenotype and attendant co-morbidities ( Table 1).…”

Impact of Glucose-Lowering Medications on Cardiometabolic Risk in Type 2 Diabetes

“…Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD); in the past, the only treatment that was able to attenuate DKD was a renin-angiotensin system blockade (ACEi or ARB) but for the partial effectiveness of these agents is needed to delay or prevent progression to ESRD. Recently reno-cardiovascular safety profile of SGLT2 inhibitors and GLP-1RAs in diabetic patients has been suggested as a second line treatment in type 2 diabetic patients when it is not contraindicated [1]. Although they have shown a reassuring safety profile, unfortunately, the current guidelines do not fully allow us to identify the most appropriate drug according to a specific patient phenotype and attendant co-morbidities.…”