SGLT-2 inhibitors and GLP-1 receptor agonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease. A consensus statement by the EURECA-m and the DIABESITY working groups of the ERA-EDTA

Abstract

Chronic kidney disease (CKD) in patients with diabetes mellitus (DM) is a major problem of public health. Currently, many of these patients experience progression of cardiovascular and renal disease, even when receiving optimal treatment. In previous years, several new drug classes for the treatment of type 2 DM have emerged, including inhibitors of renal sodium–glucose co-transporter-2 (SGLT-2) and glucagon-like peptide-1 (GLP-1) receptor agonists. Apart from reducing glycaemia, these classes were reported to have other beneficial effects for the cardiovascular and renal systems, such as weight loss and blood pressure reduction. Most importantly, in contrast to all previous studies with anti-diabetic agents, a series of recent randomized, placebo-controlled outcome trials showed that SGLT-2 inhibitors and GLP-1 receptor agonists are able to reduce cardiovascular events and all-cause mortality, as well as progression of renal disease, in patients with type 2 DM. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of SGLT-2 inhibitors and GLP-1 analogues, analyses the potential mechanisms involved in these actions and discusses their place in the treatment of patients with CKD and DM.

GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

“…By contrast, SGLT2i and some GLP-1RA were associated with improved cardiorenal outcomes. SGLT2i reduced cardiorenal risk in patients at high cardiovascular risk and in patients with DKD, as recently reported [44,45]. Cardiovascular and renal benefit is present despite only a modest reduction in weight and regardless of glycemic control.…”

Chronodisruption: A Poorly Recognized Feature of CKD

“…On the other, the longer life expectancy of the population and the increasing prevalence of risk factors for CKD such as obesity, diabetes and hypertension, together with the underdeveloped therapeutic armamentarium, are driving up the prevalence and impact of CKD. There is hope in the recent characterization of a dramatic nephroprotective impact of sodium-glucose transport protein 2 (SGLT2) inhibitors when added on top of renin angiotensin system (RAS) blockade for diabetic kidney disease and potentially other kidney diseases [4][5][6]. However, data from the hypertension field have clearly demonstrated that the availability of effective drugs is not enough, especially in polymedicated populations, where guidelines now emphasize measures to facilitate compliance [7].…”

Series: Implications of the recent CVOTs in type 2 diabetes

“…Furthermore, they will evaluate whether this renal protection also occurs independently of the presence of diabetes and thus of the glucose status. If yes, this will of course open new perspectives for the use of SGLT2s in patients with CKD and the interest for this pharmacological class might be increasingly shifted from endocrinologists to nephrologists [23,43], in a similar way as the expected shift to cardiologists as already mentioned [21].…”

“…The positive results on cardiovascular and renal outcomes profoundly influence the most recent consensus statement by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) [20]. In the meantime, other societies of cardiology [6,21,22] and nephrology [23] also published new algorithms for the management of patients with T2DM at high risk of cardiovascular (including HF) and renal complications.…”