Journal
DIABETES OBESITY & METABOLISM
Volume 19, Issue 6, Pages 809-813Publisher
WILEY
DOI: 10.1111/dom.12881
Keywords
empagliflozin; fasting plasma glucose; free fatty acid; glucagon; insulin; ketone; SGLT2 inhibitor
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Funding
- Boehringer-Ingelheim
- South Texas Veterans Health Care System
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Aim: To examine metabolic factors that influence ketone production after sodium-glucose cotransport inhibitor (SGLT2) administration. Research design and methods: Fasting plasma glucose (FPG), insulin, glucagon, free fatty acid and ketone concentrations were measured in 15 type 2 diabetes mellitus (T2DM) and 16 nondiabetic subjects before and at day 1 and day 14 after treatment with empagliflozin. Results: Empagliflozin caused a 38 mg/dL reduction in FPG concentration in T2DM patients. However, it caused only a small but significant (7 mg/dL) reduction in the FPG concentration in impaired fasting glucose (IFG) subjects and did not affect FPG concentration in normal glucose tolerant (NGT) subjects. Empagliflozin caused a significant increase in mean plasma glucagon, free fatty acid (FFA) and ketone concentrations in T2DM subjects. However, empagliflozin did not cause a significant change in mean plasma insulin, glucagon or ketone concentrations in non-diabetic subjects. An index that integrates change in plasma glucose, insulin and FFA concentration at day 1 strongly correlates with plasma ketone concentration at day 1 (r = 0.85, P < .001) and day 14 (r = 0.63, r = 0.01) and predicts, with 86% sensitivity and 83% specificity, subjects at the top tertile for plasma ketone concentration after empagliflozin treatment. Conclusion: Results of the present study demonstrate that SGLT2 inhibition exerts different metabolic effects in non-diabetic individuals as compared to diabetic patients.
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