Glycaemic Control in Diabetes

Handbook of experimental pharmacology, vol. 270, pp. 47–71

Abstract

Reduction of glucose is the hallmark of diabetes therapy proven to reduce micro- and macro-vascular risk in patients with type 1 diabetes. However glucose-lowering efficacy trials in type 2 diabetes didn't show major cardiovascular benefit. Then, a paradigm change in the treatment of patients with type 2 diabetes has emerged due to the introduction of new blood glucose-lowering agents. Cardiovascular endpoint studies have proven HbA1c-independent cardioprotective effects for GLP-1 receptor agonists and SGLT-2 inhibitors. Furthermore, SGLT-2 inhibitors reduce the risk for heart failure and chronic kidney disease. Mechanisms for these blood glucose independent drug target-related effects are still an enigma. Recent research has shown that GLP-1 receptor agonists might have anti-inflammatory and plaque stabilising effects whereas SGLT-2 inhibitors primarily reduce pre- and after-load of the heart and increase work load efficiency of the heart. In addition, reduction of intraglomerular pressure, improved energy supply chains and water regulation appear to be major mechanisms for renoprotection by SGLT-2 inhibitors. These studies and observations have led to recent changes in clinical recommendations and treatment guidelines for type 2 diabetes. In patients with high or very high cardio-renal risk, SGLT-2 inhibitors or GLP-1 receptor agonists have a preferred recommendation independent of baseline HbA1c levels due to cardioprotection. In patients with chronic heart failure, chronic kidney disease or at respective risks SGLT-2 inhibitors are the preferred choice. Therefore, the treatment paradigm of glucose control in diabetes has changed towards using diabetes drugs with evidence-based organ protection improving clinical prognosis.

Authors 5

1. Dirk Müller‐Wieland corresponding Aachen Department of Medicine I

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine I, University Hospital RWTH Aachen, Aachen, Germany. dirmueller@ukaachen.de

   Department of Medicine I, University Hospital RWTH Aachen, Aachen, Germany

2. Julia Brandts Aachen Department of Medicine I

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine I, University Hospital RWTH Aachen, Aachen, Germany

3. Marlo Verket Aachen Department of Medicine I

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine I, University Hospital RWTH Aachen, Aachen, Germany

4. Nikolaus Marx Aachen Department of Medicine I

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine I, University Hospital RWTH Aachen, Aachen, Germany

5. Katharina S. Schütt Aachen Department of Medicine I

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine I, University Hospital RWTH Aachen, Aachen, Germany