Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of glucose-lowering agent for type 2 diabetes (T2D) that are commonly used in clinical practice. With the recent disclosure of data from the CARMELINA cardiovascular outcomes trial (CVOT), which investigated linagliptin, CV and renal outcomes data are now available for four agents in the DPP-4 inhibitor class that are approved in most markets. To consider how the CARMELINA study may be interpreted, and the relevance for our clinical practice, we convened as an expert group of diabetes specialists from the Central and Eastern Europe region to discuss the new disclosures. Our discussions revealed a general confidence in safety across the class that is further supported by CARMELINA. However, we also concluded that there are important differences in the available evidence level between agents in the setting of heart failure and data on renal outcomes. Here, we noted the clinical relevance to our practice of the study population in CARMELINA, which is unique among CVOTs in including a majority of patients with chronic kidney disease (CKD). Given the risk for future development of renal impairment that is associated with T2D even in patients without current overt CKD, we believe that the CARMELINA study provides important new insights that are clinically relevant for a broad range of patients. Finally, we discuss how these insights can be integrated into the approach to the pharmacotherapeutic management of hyperglycaemia that is recommended in newly updated guidelines.

1st Medical Department Hanusch Krankenhaus Vienna Austria

2nd Department of Medicine and Nephrological Center Faculty of Medicine University of Pécs Hungary

3rd Department of Internal Medicine 1st Faculty of Medicine Charles University Prague Prague Czech Republic

Clinic for Endocrinology Diabetes and Metabolic Diseases CCS Faculty of Medicine University of Belgrade Belgrade Serbia

Department of Diabetes Nutrition and Metabolic Diseases Carol Davila University of Medicine and Pharmacy Bucharest Romania

Department of Endocrinology and Diabetology University Hospital Center Rijeka Faculty of Medicine University of Rijeka Rijeka Croatia

Department of Endocrinology Medical University of Sofia Bulgaria

Division of Nephrology Department of Medicine Würzburg University Clinic Würzburg Germany

Endocrinology Clinic Clalit Health Services Jerusalem Israel

Endocrinology Research Centre Moscow Russia

Medical University of Silesia Katowice Poland

Medical University of Vienna Vienna Austria

National Medical Academy for Postgraduate Education Kiev Ukraine

Sheba Medical Center and Tel Aviv University Tel Aviv Israel

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Worldwide inertia to the use of cardiorenal protective glucose-lowering drugs (SGLT2i and GLP-1 RA) in high-risk patients with type 2 diabetes