Journal Article

Renal hemodynamic effects differ between antidiabetic combination strategies: randomized controlled clinical trial comparing empagliflozin/linagliptin with metformin/insulin glargine

Bosch, Agnes, Schiffer, Mario, Kolwelter, Julie, Jung, Susanne, Bramlage, Peter, Ott, Christian, Kannenkeril, Dennis, Schmieder, Roland E., Korn, Manuel, Striepe, Kristina

2021

Overview

Background Type 2 diabetes causes cardio-renal complications and is treated with different combination therapies. The renal hemodynamics profile of such combination therapies has not been evaluated in detail. Methods Patients (N = 97) with type 2 diabetes were randomized to receive either empagliflozin and linagliptin (E+L group) or metformin and insulin glargine (M+I group) for 3 months. Renal hemodynamics were assessed with para-aminohippuric acid and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR). Intraglomerular hemodynamics were calculated according the Gomez´ model. Results Treatment with E+L reduced GFR (p = 0.003), but RPF remained unchanged (p = 0.536). In contrast, M+I not only reduced GFR (p = 0.001), but also resulted in a significant reduction of RPF (p < 0.001). Renal vascular resistance (RVR) decreased with E+L treatment (p = 0.001) but increased with M+I treatment (p = 0.001). The changes in RPF and RVR were different between the two groups (both p adjust  < 0.001). Analysis of intraglomerular hemodynamics revealed that E+L did not change resistance of afferent arteriole (R A ) (p = 0.116), but diminished resistance of efferent arterioles (R E ) (p = 0.001). In M+I group R A was increased (p = 0.006) and R E remained unchanged (p = 0.538). The effects on R A (p adjust  < 0.05) and on R E (p adjust  < 0.05) differed between the groups. Conclusions In patients with type 2 diabetes and preserved renal function treatment with M+I resulted in reduction of renal perfusion and increase in vascular resistance, in contrast to treatment with E+I that preserved renal perfusion and reduced vascular resistance. Moreover, different underlying effects on the resistance vessels have been estimated according to the Gomez model, with M+I increasing R A and E+L predominantly decreasing R E , which is in contrast to the proposed sodium-glucose cotransporter 2 inhibitor effects. Trial registration : The study was registered at www.clinicaltrials.gov (NCT02752113) on April 26, 2016

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Aged / Angiology / Antidiabetics / Arterioles / Benzhydryl Compounds - adverse effects / Benzhydryl Compounds - therapeutic use / Body mass index / Cardiology / Creatinine / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - diagnosis / Diabetes Mellitus, Type 2 - drug therapy / Diabetic Nephropathies - diagnosis / Diabetic Nephropathies - etiology / Diabetic Nephropathies - physiopathology / Diabetic Nephropathies - prevention & control / Dipeptidyl-Peptidase IV Inhibitors - adverse effects / Dipeptidyl-Peptidase IV Inhibitors - therapeutic use / Drug Therapy, Combination / Fasting / Female / Germany / Glomerular filtration rate / Glomerular Filtration Rate - drug effects / Glucose / Glucosides - adverse effects / Glucosides - therapeutic use / Heart failure / Hemodynamics / Hemodynamics - drug effects / Humans / Hypoglycemic Agents - adverse effects / Hypoglycemic Agents - therapeutic use / Insulin / Insulin Glargine - adverse effects / Insulin Glargine - therapeutic use / Intraglomerular / Inulin / Linagliptin - adverse effects / Linagliptin - therapeutic use / Male / Medicine / Medicine & Public Health / Metformin / Metformin - adverse effects / Metformin - therapeutic use / Middle Aged / Na+/glucose cotransporter / Original Investigation / Patients / Perfusion / Plasma / Prospective Studies / Renal / Renal function / Renal Plasma Flow - drug effects / Sensory neurons / Sodium-Glucose Transporter 2 Inhibitors - adverse effects / Sodium-Glucose Transporter 2 Inhibitors - therapeutic use / Time Factors / Treatment Outcome / Type 2 diabetes