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

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 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.

SUBMITTER: Ott C

PROVIDER: S-EPMC8418746 | biostudies-literature |

REPOSITORIES: biostudies-literature

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