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Empagliflozin Enhances Hepatic Glucose Production and Reduces Total-Body Norepinephrine Turnover Rate: A Randomized Trial

Abdelgani S, Khattab A, Adams JM, Al-Mulla F, Abu-Farha M, Baskoy G, Abubaker J, Merovci A et al.

Diabetes, 2025

Abstract

Article highlights: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) cause an increase in hepatic glucose production (HGP). We previously showed that SGLT2i cause a rapid (within 4 h) increase in the total-body norepinephrine (NE) turnover rate, which could explain the increase in HGP. Because the increase in HGP caused by SGLT2i is long-lasting, we examined the long-term effect of SGLT2i on the NE turnover rate. Empagliflozin caused a decrease in total-body NE turnover at 1 day and at 12 weeks after starting therapy, despite an increase in glucose production, and the magnitude of decrease in NE turnover inversely correlated with the increase in HGP caused by empagliflozin.

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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.

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