Kidney Week

Abstract: SA-OR083

Combination Therapy of Empagliflozin and Linagliptin vs. Metformin and Insulin Glargine on Intra- and Renal Hemodynamics in Type 2 Diabetes

Session Information

• Moving the Needle for Treatment of Diabetic Kidney Disease
  November 09, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
  Abstract Time: 05:30 PM - 05:42 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Ott, Christian, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany

Christian Ott, MD

• Kannenkeril, Dennis, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany

Dennis Kannenkeril,

• Jung, Susanne, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany

Susanne Jung,

• Schmieder, Roland E., Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany

Roland E. Schmieder,

Background

Combination of insulin with oral antidiabetic drugs is a valid option, but oral combination therapy emerged as an alternative treatment in type 2 diabetes (T2DM). However, the intra-, and renal hemodynamic profile of such combinations therapies has not been evaluated so far.

Methods

In this study 101 patients with T2DM were randomized to receive either empagliflozin 10mg and linagliptin 5mg (E+L group) orally or metformin and insulin glargine (M+I group, with dose adjustments according to glucose levels), for 3 months. Renal hemodynamics were assessed with the “gold-standard”, namely constant-infusion input-clearance technique with para-aminohippuric acid and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR). Intrarenal hemodynamics were calculated according the model established by Gomez.

Results

Due to the multiple dose adjustment of insulin glargine, reduction in HbA1c was greater in M+I than in E+L group (p=0.001), hence all analyses between M+I and E+L were HbA1c-adjusted to evaluate the glucose independent effects between the 2 therapies. In E+L group, body weight (p<0.001), body mass index (p<0.001) and both ambulatory 24-h systolic and diastolic BP (p=0.004/0.036) were reduced compared to M+I group.
Treatment with E+L reduced GFR (127±13 vs. 120±14 ml/min, p=0.003), but RPF remained unchanged (623±114 vs. 615±115 ml/min, p=0.536). In contrast, treatment with M+I not only reduced GFR (127±15 vs. 120±13 ml/min, p=0.001), but also resulted in a significant reduction of RPF (653±150 vs. 600±121 ml/min, p<0.001) that was different between the 2 groups (p<0.001). Analysis of intrarenal hemodynamics revealed that E+L did not significantly impact on resistance of afferent arteriole (R_A) (p=0.116), but diminished resistance of efferent arteriole (R_E) (p=0.001), whereas in M+I group R_A was reduced (p=0.006) and R_E remained unchanged (p=0.538). Thus, the effects on R_A (p<0.001) and on R_E (p<0.001) were significantly different between the 2 groups.

Conclusion

As expected combination therapy with E+L reduced GFR, whereas M+I resulted in both reduction of GFR and RPF. Analysis of intrarenal hemodynamics identified different underlying hemodynamic mechanism, with E+L (surprisingly) mainly decreasing R_E and M+I affecting R_A.

Funding

• Commercial Support – Boehringer Ingelheim