Journal of Clinical and Translational Endocrinology Case Reports (Jun 2024)

Hyperglycemic DKA in a patient with type 2 diabetes mellitus on monotherapy with SGLT-2 inhibitor

  • Luis A. Medina Mora,
  • Samihah Ahmed,
  • Angelica M. Sanchez Ruiz,
  • Leonid Poretsky

Journal volume & issue
Vol. 32
p. 100166

Abstract

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Background/objective: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are known to increase the risk of euglycemic diabetic ketoacidosis (DKA). Hyperglycemic DKA (hDKA), however, is not a common side effect of SGLT-2 inhibitor monotherapy. Case report: We present a case of hyperglycemic DKA in a middle-aged Caucasian male with a history of type 2 diabetes on monotherapy with an SGLT-2 inhibitor, no history of insulin deficiency or evidence of autoimmune diabetes and no precipitating factors for DKA at presentation. The patient was discharged from the hospital on insulin therapy after resolution of DKA and was transitioned to an oral anti-hyperglycemic regimen which did not include SGLT-2 inhibitors. Close outpatient follow up subsequently revealed declining C-peptide levels and increasing hemoglobin A1C levels without any episodes of DKA. Discussion: The mechanisms by which SGLT-2 inhibitors cause hDKA are not fully understood and likely involve hyperglucagonemia. Inhibition of SGLT-2 by dapagliflozin has been shown to paradoxically trigger glucagon secretion at higher glucose concentrations possibly due to direct effects on KATP channel activation and membrane depolarization in pancreatic α-cells. Conclusion: We conclude that monotherapy with SGLT-2 inhibitors presents a risk of not just euglycemic, but also hyperglycemic diabetic ketoacidosis in patients with type 2 diabetes and declining endogenous insulin production.

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