Effects of dapagliflozin on urinary metabolites in people with type 2 diabetes

Abstract

Aim: To assess the effects of the sodium-glucose co-transporter-2 (SGLT2) inhibitor dapagliflozin on a pre-specified panel of 13 urinary metabolites linked to mitochondrial metabolism in people with type 2 diabetes and elevated urine albumin levels. Materials and methods: Urine and plasma samples were used from a double-blind, randomized, placebo-controlled crossover trial in 31 people with type 2 diabetes, with an albumin:creatinine ratio >100 mg/g, and who were on a stable dose of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Dapagliflozin or placebo treatment periods each lasted 6 weeks, with a 6-week washout period in between. Urinary and plasma metabolites were quantified by gas-chromatography mass spectrometry, corrected for creatinine level, and then combined into a single-valued urinary metabolite index. Fractional excretion of the metabolites was calculated. Results: All 13 urinary metabolites were detectable. After 6 weeks of dapagliflozin therapy, nine of the 13 metabolites were significantly increased from baseline. The urinary metabolite index increased by 42% (95% confidence interval [CI] 8.5 to 85.6; P =.01) with placebo versus 121% (95% CI 69 to 189; P