Determinants of the increase in ketone concentration during SGLT2 inhibition in NGT, IFG and T2DM patients

Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Curtis Triplitt, Ralph A. DeFronzo, Muhammad Abdul-Ghani

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


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 non-diabetic 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.

Original languageEnglish (US)
Pages (from-to)809-813
Number of pages5
JournalDiabetes, Obesity and Metabolism
Issue number6
StatePublished - Jun 2017


  • SGLT2 inhibitor
  • empagliflozin
  • fasting plasma glucose
  • free fatty acid
  • glucagon
  • insulin
  • ketone

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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