Abstract: FR-PO650

The Effects of Dapagliflozin on Urinary Metabolites in Patients with Type 2 Diabetes

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Pena, Michelle, University Medical Center Groningen, Groningen, Netherlands
  • Mulder, Skander, University Medical Center Groningen, Groningen, Netherlands
  • Darshi, Manjula, University of California San Diego, La Jolla, California, United States
  • Van espen, Benjamin Fj, University of California San Diego, La Jolla, California, United States
  • Kim, Jiwan John, University of California San Diego, La Jolla, California, United States
  • Sharma, Kumar, University of California San Diego, La Jolla, California, United States
  • Lambers Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
Background

The cardiovascular and possibly kidney protective effects of SGLT2 inhibition are hypothesized in part due to improved mitochondrial function in the heart and kidney. To test this, we assessed the effects of dapagliflozin, an SGLT2 inhibitor, on a pre-specified panel of 13 urinary metabolites known to reflect mitochondrial function in patients with diabetes and elevated albuminuria.

Methods

Urine samples were used from a double-blind, randomized, placebo controlled crossover trial in 28 patients with type 2 diabetes, albumin/creatinine ratio >100 mg/g, and on a stable dose of an Angiotensin Converting Enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). Dapagliflozin and placebo treatment periods each lasted for 6 weeks. Urinary metabolites were quantified by gas-chromatography mass spectrometry, corrected for urinary creatinine, and combined into a single-valued index.

Results

Twelve of the 13 metabolites were detectable. At baseline, higher values of the metabolite index positively correlated with eGFR (pearson's r = 0.36, p = 0.05). Preliminary findings showed that after 6 weeks of dapagliflozin treatment, eight of the 12 metabolites were significantly increased from baseline. The metabolite index increased by 17% (95%CI: -3 – 49, p = 0.14) with placebo compared to 60% (26 – 102, p <0.001) with dapaglifozin. Accordingly, the placebo-adjusted effect was 45% (2 – 76, p = 0.03). Changes in the metabolite index during dapagliflozin treatment did not correlate with changes in HbA1c (r = 0.21, p = 0.28), eGFR (r = -0.16, p = 0.42), or albuminuria (r = 0.18, p = 0.37).

Conclusion

Dapagliflozin significantly increased a panel of mitochondrial metabolites previously associated with progressive diabetic kidney disease. These data suggest that SGLT2 inhibitors may improve mitochondrial function leading to kidney protection. Future studies of longer treatment duration and clinical outcomes are needed to confirm the clinical impact of these findings.