Primary versus secondary cardiorenal prevention in type 2 diabetes: Which newer anti‐hyperglycaemic drug matters?

Abstract

We are observing a resurgence of major diabetic vascular complications after a period of dramatic decrease during the period 1990 to 2010. The classical division of cardiovascular prevention into primary (with an event) and secondary (without an event) is largely used to describe cardiovascular risk in type 2 diabetes (T2D); however, there is evidence that the cardiovascular risk in diabetes may range from highest in patients who experienced a previous cardiovascular event to mild in patients with the main risk factors at target. Herein, we present details of the 14 cardiovascular outcome trials (CVOTs) published to date, including the total population investigated, and their separation into primary (T2D + multiple risk factors) and secondary prevention (T2D + established cardiovascular disease [CVD]) populations as detailed within the trials. We also summarize evidence for the effects of dipeptidyl peptidase‐4 inhibitors (DPP‐4i), glucagon‐like peptide‐1 receptor agonists (GLP1‐RA) and sodium glucose co‐transporter‐2 inhibitors (SGLT‐2i) versus placebo on the risk of major cardiovascular events (MACE), heart failure (HF) and diabetic kidney disease (DKD). In primary prevention, SGLT‐2i reduce both the risk of hospitalization for HF and progression of DKD; in secondary prevention, SGLT‐2i are effective on the three endpoints, DPP‐4i are neutral, while GLP1‐RA show mixed results.

Preventing major adverse cardiovascular events by SGLT-2 inhibition in patients with type 2 diabetes: the role of kidney

“…Overall, these findings have allowed to identify CKD as a "coronary heart disease risk equivalent" as it was recognized for T2D. With the notable difference that T2D may no longer be a risk equivalent for coronary heart disease if all risk factors (glycemia, blood pressure, LDLcholesterol, body weight, smoking) are being controlled by treatment (drug and/or lifestyle) [13,14]; this may not the case for CKD as its current therapeutic armamentarium does not restore to normal albuminuria, eGFR, or both. CKD also acts as major predisposing risk factor also for stroke and peripheral artery disease [15,16].…”

Sodium–glucose transporter-2 inhibitors for prevention and treatment of cardiorenal complications of type 2 diabetes

“…The distinction between primary and secondary prevention risk categories in diabetes is no longer reported in European Society of Cardiology guidelines on diabetes, pre-diabetes, and CVD developed in collaboration with the European Association for the Study of Diabetes [63]. Accordingly, the CV risk in patients with T2D may range from the highest risk in patients who experienced a previous CV event, to a mild risk in patients with the main risk factors within target ranges, a very small category of about 5%-6% of patients [5,6,63,64]. The CVOTs used to distinguish T2D patients with established CVD (secondary prevention), that is, those having experienced a previous event or with evidence of more than 50% stenosis in an epicardial coronary artery, and patients without established CVD (primary prevention), i.e.…”

Nephroprotection by SGLT2 Inhibition: Back to the Future?

“…Overall, the results of the four large RCTs demonstrated, along with cardiovascular benefits [ 12 , 13 ], a major nephroprotective efficacy of SGLT2i, with a significant 30% reduction in albuminuria and a 30–40% lower risk of progression to ESKD. These beneficial effects were further enhanced by optimal RAS inhibition as background therapy in most patients.…”

“…This discrepancy is relevant because the current guidelines recommend GLP1-RA as a therapeutic alternative to SGLT2i for organ protection in DM2 [ 48 , 49 , 50 ]. Indeed, trials have demonstrated that therapy with GLP-1RA reduces the risk of the composite renal endpoint (albuminuria, doubling of serum creatinine or decline in eGFR, end-stage kidney disease or death from a renal cause) by about 5–10%; however, this result is exclusively dependent on the antialbuminuric effect [ 12 ]. It is, therefore, possible that GLP-1RA may be nephroprotective by means of antialbuminuric effects other than changes in intrarenal hemodynamics, namely the reduction in glycemia, body weight, BP, endothelial dysfunction and inflammation.…”