Insulin Sensitivity in Type 2 Diabetes Improved With Dapagliflozin

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Dapagliflozin improved insulin sensitivity in type 2 diabetes.
Dapagliflozin improved insulin sensitivity in type 2 diabetes.

HealthDay News -- Dapagliflozin improves insulin sensitivity and increases lipid oxidation and plasma ketone concentration in patients with type 2 diabetes, according to a study published online Aug. 25 in Diabetes Care.

Giuseppe Daniele, from the University of Texas Health Science Center at San Antonio, and colleagues randomly assigned 18 individuals with type 2 diabetes to dapagliflozin or placebo in a 1:1 ratio. Subjects received an insulin clamp with tritiated glucose, indirect calorimetry, and muscle biopsies before and after 2 weeks.

The researchers found that fasting plasma glucose was reduced, and insulin-stimulated glucose disposal was increased by 36% (P<.01) with dapagliflozin. There was a decrease in glucose oxidation (P<.05), while nonoxidative glucose disposal increased (P=.03). Basal glucose oxidation decreased with dapagliflozin, and there was an increase in lipid oxidation and plasma ketone concentration (P<.01) in association with an increase in fasting plasma glucagon (P<.01). 

There was a reduction in the adenosine triphosphate synthesis rate with dapagliflozin, which correlated with an increase in the concentration of plasma ketones.

"Dapagliflozin improved insulin sensitivity and caused a shift from glucose to lipid oxidation, which, together with an increase in glucagon-to-insulin ratio, provide the metabolic basis for increased ketone production," the researchers wrote.

Disclosures: One author disclosed financial ties to pharmaceutical companies, including AstraZeneca, which manufactures dapagliflozin.

Reference

  1. Daniele G, Xiong J, Solis-Herrera C, et al. Dapagliflozin enhances fat oxidation and ketone production in patients with type 2 diabetes. Diabetes Care. 2016. doi:10.2337/dc15-2688.
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