Diabetes and kidney disease: emphasis on treatment with SGLT-2 inhibitors and GLP-1 receptor agonists

• Published in: Metabolism, clinical and experimental Vol. 120; p. 154799
• Main Authors: Prattichizzo, Francesco, de Candia, Paola, Ceriello, Antonio
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.07.2021
• Subjects: Blood pressure; Diabetes complications; Diabetes mellitus; Diabetes treatment algorithm; Epigenetics; GLP-1; Glucose control; Low-grade inflammation; miRNAs; Nephropathy; Oxidative stress; SGLT-2; Low-grade inflammation; Oxidative stress; Nephropathy; GLP-1; Diabetes complications; miRNAs; Diabetes mellitus; Diabetes treatment algorithm; Epigenetics; Blood pressure; Glucose control; SGLT-2
• ISSN: 0026-0495; 1532-8600; 1532-8600
• DOI: 10.1016/j.metabol.2021.154799

Kidney disease is a frequent microvascular complication of both type 1 and type 2 diabetes. Historic trials have demonstrated that a tight glycaemic control is the most powerful approach to decrease the chances of developing diabetic nephropathy. However, having an HbA1c < 7% does not completely suppress the risk of kidney disease. The observed residual risk is likely ascribable to two phenomena: 1- the presence of risk factors and alterations additive to and independent of glycaemia, and 2- the activation of long-lasting imbalances by periods of exposure to uncontrolled glycemia, a phenomenon referred to as metabolic memory or legacy effect. Long-lasting oxidative stress, epigenetic alterations, cellular senescence, and the resulting chronic low-grade inflammation are all candidate mechanisms explaining the development of nephropathy despite proper control of risk factors. Recently, two classes of drugs, i.e. glucagon-like peptide (GLP) 1 receptor agonists (RA) and sodium-glucose transporter 2 inhibitors (SGLT-i) have changed this scenario. Indeed, cardiovascular outcome and other trials have clearly shown a renoprotective effect for these drugs, well-beyond their glucose-lowering properties. In this review, we summarize: 1- selected key trials and mechanisms underlying the development of diabetic kidney disease and 2- the results relative to renal endpoints in clinical trials of GLP-1 RA and SGLT-2i. Then, we briefly discuss some of the hypotheses posited to explain the marked renoprotective properties of these two classes, evidencing the still existing gaps in knowledge and proposing future directions to further implement the use of these powerful, disease-modifying drugs. •Tight glycaemic control and proper blood pressure management reduce the incidence and progression of diabetic kidney disease.•Long-lasting oxidative stress, epigenetic alterations, cellular senescence, and the resulting chronic low-grade inflammation are held to underlie the development of diabetic nephropathy.•GLP-1 receptor agonists showed favourable renal outcomes in patients with type 2 diabetes and cardiovascular diseases.•SGLT-2 inhibitors reduced the progression of nephropathy and the incidence of cardiovascular outcomes in a range of patients, irrespective of diabetes status, renal impairment, and the presence/absence of heart failure.•The mechanisms underpinning the benefit of GLP-1 receptor agonists and SGLT-2 inhibitors on the cardiorenal axis are subject of investigation, but are likely pleiotropic.