Dapagliflozin Significantly Impacts Urine Metabolome in Individuals With T2D

Dapagliflozin significantly impacts the urine metabolome of individuals with type 2 diabetes (T2D) independent of glucose-lowering, according to the results of a study published in The Journal of Clinical Endocrinology & Metabolism.

Though research has shown sodium glucose co-transporters-2 (SGLT-2) inhibitors improve mitochondrial function, these studies either used plasma metabolomics as a measurement or studied individuals with established diabetic nephropathy, resulting in a lack of urine metabolite data for individuals with normal renal functioning.

To evaluate the effect of the SGLT-2 inhibitor dapagliflozin of individuals with early-onset T2D and normal renal functioning, proton-nuclear magnetic resonance (¹H-NMR)-based urine metabolomic signature data from 133 patients were analyzed. 80 individuals with T2D on metformin monotherapy (≥2000mg/day) with hemoglobin A1C (HbA_1C) >7% were included. 50 of these individuals were treated with 10 mg of dapagliflozin daily for 3 months and 30 were treated with insulin degludec for 3 months for comparison. Dietary habits and existing medications were kept constant. 53 individuals without T2D served as healthy controls. Overnight fasting blood and urine samples were collected in the morning at baseline and at the end of the treatment period.

Individuals in the dapagliflozin group experienced significant increases in serum creatinine and serum phosphate levels from baseline (P =.005). Renal fractional excretion values increased proportionally. Dapagliflozin treatment significantly altered the quantities of 27 of the 70 metabolites measured in the ¹H-NMR spectrum of urine (P <.0005). Individuals in the insulin degludec group did not experience significant changes in plasma and urine metabolic parameters from baseline apart from a decrease in HbA_1C and blood glucose (P =.001).

Taken together, the results of this analysis demonstrated that patients with T2D exhibit altered serum and urine metabolic profiles after being treated with the SGLT-2 inhibitor dapagliflozin. According to the authors, most of the observed changes “can be considered beneficial and may contribute to the renoprotective properties of dapagliflozin.”

Limitations to the study include the existence of some slight differences between the dapagliflozin and insulin groups at baseline, which may make differences from baseline difficult to compare between groups.

Future research confirming the results of this study and with more similar groups at baseline are warranted.

Disclosure

The funding for this study was provided by AstraZeneca, the manufacturer of Farxiga, a dapagliflozin medication.

Reference

Bletsa E, Filippas-Dekouan S, Kostara C, et. al. Effect of dapagliflozin on urine metabolome in patients with type 2 diabetes. [published online February 6, 2021].  J Clin Endocrinol Metab. doi:10.1210/clinem/dgab086