SGLT2i Increase Endogenous Glucose Production: That’s Good News!

In this issue of Diabetes Care, Alatrach et al. (1) present an investigation into the effects of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on endogenous glucose production (EGP) in patients with type 2 diabetes during an 8-h fast and after an oral glucose load. The study included 48 patients divided into four groups: dapagliflozin (DAPA), exenatide (EXE), DAPA/EXE, and placebo (PCB). The first protocol evaluated EGP response to therapy after an 8-h tracer infusion. Results showed that EGP decreased with PCB and EXE and remained unchanged with DAPA and DAPA/EXE. In protocol 2, patients were restudied with a state-of-the-art 5-h double-tracer oral glucose tolerance test. EGP decreased with PCB and EXE, while with DAPA and DAPA/EXE the decrease in EGP was attenuated. The authors accurately measured insulin and glucagon concentrations, the two main regulators of EGP. However, neither hormonal changes nor their ratio completely justified the blunted suppression of EGP by DAPA, prompting the authors to suggest that additional factors must be involved.

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