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

Ott C, Jung S, Korn M, Kannenkeril D, Bosch A, Kolwelter J, Striepe K, Bramlage P, Schiffer M, Schmieder R (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 20

Article Number: 178

Journal Issue: 1

DOI: 10.1186/s12933-021-01358-8

Abstract

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 padjust < 0.001). Analysis of intraglomerular hemodynamics revealed that E+L did not change resistance of afferent arteriole (RA) (p = 0.116), but diminished resistance of efferent arterioles (RE) (p = 0.001). In M+I group RA was increased (p = 0.006) and RE remained unchanged (p = 0.538). The effects on RA (padjust < 0.05) and on RE (padjust < 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 RA and E+L predominantly decreasing RE, 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

Authors with CRIS profile

Involved external institutions

Institut für Pharmakologie und präventive Medizin (IPPMed GmbH) Germany (DE)

How to cite

APA:

Ott, C., Jung, S., Korn, M., Kannenkeril, D., Bosch, A., Kolwelter, J.,... Schmieder, R. (2021). Renal hemodynamic effects differ between antidiabetic combination strategies: randomized controlled clinical trial comparing empagliflozin/linagliptin with metformin/insulin glargine. Cardiovascular Diabetology, 20(1). https://doi.org/10.1186/s12933-021-01358-8

MLA:

Ott, Christian, et al. "Renal hemodynamic effects differ between antidiabetic combination strategies: randomized controlled clinical trial comparing empagliflozin/linagliptin with metformin/insulin glargine." Cardiovascular Diabetology 20.1 (2021).

BibTeX: Download