Ketoacidosis Due to Empagliflozin, a Paradigm Shift: Case Report and Review of Literature

Author(s): Carlos Hernandez-Quiles*, Nieves Ramirez-Duque, Domingo Acosta-Delgado .

Journal Name: Current Diabetes Reviews

Volume 15 , Issue 4 , 2019

Become EABM
Become Reviewer

Abstract:

Introduction: Sodium-glucose cotransporter 2(SGLT2)-inhibitors are new antihyperglycemic agents that have shown a reduction in cardiovascular events in type 2 diabetes mellitus. Recent warnings have been developed about an increased risk of euglycemic and moderate hyperglycemic diabetic ketoacidosis with the use of SGLT2 inhibitors, but its real incidence is not available yet.

Case Report: We present a case of DKA with moderate hyperglycemia in a patient treated with metformin and empagliflozin.

Conclusion: DKA in patients treated with SGLT2 inhibitors can be presented as euglycemic and moderated hyperglycemia. This special presentation poses a physician’s challenge.

Keywords: Sodium glucose cotransporter 2, SGLT2 inhibitors, empagliflozin, diabetes mellitus, euglycemia , diabetic ketoacidosis.

[1]
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373(22): 2117-28.
[2]
U.S. Food and Drug Administration. Drug safety communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm (Accessed on: December 4, 2015).
[3]
Rawla P, Vellipuram AR, Bandaru SS, Pradeep Raj J. Euglycemic diabetic ketoacidosis: A diagnostic and therapeutic dilemma. Endocrinol Diabetes Metab Case Rep 2017; 2017: 17-0081.
[4]
Modi A, Agrawal A, Morgan F. Euglycemic diabetic ketoacidosis: A review. Curr Diabetes Rev 2017; 13(3): 315-21.
[5]
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377(7): 644-57.
[6]
Levine MJ. Empagliflozin for Type 2 Diabetes Mellitus: An Overview of Phase 3 Clinical Trials. Curr Diabetes Rev 2017; 13(4): 405-23.
[7]
Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016; 375(4): 323-34.
[8]
AstraZeneca. Multicenter trial to evaluate the effect of Dapagliflozin on the incidence of cardiovascular events (DECLARETIMI58). Jan 2017; Available from: ttps://clinicaltrials.gov/ct2/show/NCT01730534?term=dapagliflozin+outcome&rank=6
[9]
Bilezikian JP, Watts NB, Usiskin K, et al. Evaluation of bone mineral density and bone biomarkers in patients with type 2 diabetes treated with canagliflozin. J Clin Endocrinol Metab 2016; 101(1): 44-51.
[10]
Watts NB, Bilezikian JP, Usiskin K, et al. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2016; 101(1): 157-66.
[11]
Henry RR, Thakkar P, Tong C, Polidori D, Alba M. Efficacy and safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to insulin in patients with type 1 diabetes. Diabetes Care 2015; 38(12): 2258-65.
[12]
Erondu N, Desai M, Ways K, Meininger G. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care 2015; 38(9): 1680-6.
[13]
Blau JE, Tella SH, Taylor SI, Rother KI. Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data. Diabetes Metab Res Rev 2017; 33(8)
[14]
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377(7): 644-57.
[15]
Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig 2016; 7(2): 135-8.
[16]
European Medicines Agency. uropean database of suspected adverse drug reaction report. Available online: http://www.ema.europa.eu/ema/index.jsp%3Fcurl=pages/medicines/landing/epar_search.jsp%26mid=WC0b01ac058001d124
[17]
American Diabetes Association. Standards of Medical Care in Diabetes—2017. Diabetes Care Volume 40, Supplement 1, January . 2017.
[18]
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359(15): 1577-89.
[19]
U.S. Food and Drug Administration (FDA). Glucophage (metformin hydrochloride tablets) 2008.
[20]
Eppenga WL, Lalmohamed A, Geerts AF, et al. Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: A population-based cohort study. Diabetes Care 2014; 37(8): 2218-24.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 15
ISSUE: 4
Year: 2019
Page: [259 - 262]
Pages: 4
DOI: 10.2174/1573399814666180726114044
Price: $58

Article Metrics

PDF: 52
HTML: 3
EPUB: 2
PRC: 1