Euglycemic Diabetic Ketoacidosis in a Patient With Type 2 Diabetes After Treatment With Empagliflozin

Roach, Paris; Skierczynski, Paul

doi:10.2337/dc15-1797

Cited by 37 publications

(29 citation statements)

References 2 publications

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“…In 2016, a case of euDKA was reported in a patient with advanced insulin-dependent T2DM who discontinued insulin therapy completely after starting empagliflozin. 6 A case of euDKA reported in Japan was precipitated by a low carbohydrate diet in a patient whose diabetes regimen had recently been changed from glimepiride, metformin, and linagliptin to ipraglaflozin alone. 7 A case of recurrent euDKA along with acute elevation of creatinine (from 0.6 to 1.19) was reported in a patient with a solitary kidney who underwent elective abdominoplasty.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Ketosis in a Patient With Euglycemic Diabetic Ketoacidosis Secondary to Dapagliflozin

Pujara

Ioachimescu

2017

Journal of Investigative Medicine High Impact Case Reports

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Since the approval of sodium-glucose cotransporter 2 (SGLT2) inhibitors by the US Food and Drug Administration for type 2 diabetes, there have been several reports of euglycemic diabetic ketoacidosis in patients using this class of medication. We present a case of euglycemic diabetic ketoacidosis where ketonemia and glucosuria persisted well beyond the expected effect of dapagliflozin. Our patient is a 50-year-old woman with type 2 diabetes since age 35 who was taking metformin and dapagliflozin. She presented with fatigue, constipation, and 3 days of reduced oral intake. Laboratory data indicated anion gap acidosis, ketonemia, severe hypokalemia, and minimally elevated blood glucose. She was treated with sliding scale short-acting insulin and electrolyte replacement until hospital day 6, when endocrinology was consulted. An insulin drip was initiated due to persistent ketonemia and reopening of the anion gap, despite improved oral intake and normoglycemia. On stopping the insulin drip on day 9, the β-hydroxybutyrate increased again. It finally stabilized within normal range with the initiation of basal subcutaneous insulin. This case indicates that clinical effects of dapagliflozin persist much longer than the reported half-life of 12.9 hours would predict. To prevent this potentially dangerous complication, patients taking SGLT2 inhibitors who become ill should discontinue the medication, undergo ketone evaluation, and start basal insulin, if ketones are positive. In addition, patients should be educated to stop their SGLT2 inhibitor at least 1 week prior to elective procedures.

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Section: Discussionmentioning

confidence: 99%

Prolonged Ketosis in a Patient With Euglycemic Diabetic Ketoacidosis Secondary to Dapagliflozin

Pujara

Ioachimescu

2017

Journal of Investigative Medicine High Impact Case Reports

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“…Postmarketing reports of serious cases of diabetic ketoacidosis (DKA) resulting in emergency department visits or hospitalization have been recorded for a small number of patients treated with SGLT2 inhibitors; most patients had T2D but some cases of DKA in patients with T1D were also reported, implying off‐label use . Some of these cases of DKA have occurred in patients without significant hyperglycemia and were therefore diagnosed as “euglycemic diabetic ketoacidosis.” Published case reports have also documented episodes of DKA in patients receiving SGLT2 inhibitors in patients with T1D (i.e., off‐label use) and T2D . These reports indicate that the occurrence of DKA is rare and is possibly triggered by factors such as acute febrile illness, reduced calorie intake, reduced insulin dose, and causes of pancreatic insufficiency .…”

Section: Safety and Tolerability Of Sglt2 Inhibitors Related To Mechamentioning

confidence: 93%

“…In patients with T1D and those with T2D, the association between improved glycemic control and the reduced risk of microvascular complications is well established. The efficacy of canagliflozin, dapagliflozin, and empagliflozin in lowering elevated blood glucose concentrations is well documented . However, the positive effect observed with these SGLT2 inhibitors on nonglycemic factors, such as body weight and BP, as well as their potential role in protecting renal function, may confer additional health benefits to patients with T2D.…”

mentioning

confidence: 99%

Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Nonglycemic Outcomes in Patients with Type 2 Diabetes

Trujillo

Nuffer

2017

Pharmacotherapy

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The efficacy of the sodium‐glucose cotransporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin in reducing hyperglycemia in patients with type 2 diabetes is well documented. In addition, positive effects have been observed with these agents on nonglycemic variables, such as reductions in body weight and blood pressure, which may confer additional health benefits. SGLT2 inhibitors are also associated with evidence of renal‐protecting benefits. Furthermore, during the landmark Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA‐REG OUTCOME) trial, a substantial reduction in major adverse cardiovascular outcomes was demonstrated with empagliflozin therapy. In view of the complex pathogenesis of cardiovascular disease in patients with diabetes, a pharmacologic intervention for type 2 diabetes that produces a multifaceted reduction in cardiovascular disease risk, separate from glycemic control alone, would be advantageous. Although SGLT2 inhibitors are generally well tolerated, they are associated with an increased risk of genital mycotic infections, as well as the potential risk for serious adverse events such as dehydration, development of diabetic ketoacidosis, serious urinary tract infections, and bone fractures. The findings of ongoing research will help to determine the magnitude and clinical importance of these adverse events and whether the findings of EMPA‐REG OUTCOME represent a class effect for SGLT2 inhibition or are specific to empagliflozin and will further elucidate the future role of SGLT2 inhibitors in the individualized management of patients with type 2 diabetes. In this article, we discuss the nonglycemic outcomes associated with SGLT2 inhibitor therapy in patients with type 2 diabetes as well as the clinical implications of these agents.

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“…A total of 102 events were subsequently identified by the European Medicines Agency (EMA) via EudraVigilance . Since then, several case reports have been published and DKA is now a recognized rare side‐effect of SGLT‐2i (1 in 1000)…”

Section: Conflict Of Interestmentioning

confidence: 99%

A case series of DKA occurring in patients receiving treatment with SGLT‐2 inhibitors

Bashir

Nalla

Peter

et al. 2018

Diabetes Obesity Metabolism

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Euglycemic Diabetic Ketoacidosis in a Patient With Type 2 Diabetes After Treatment With Empagliflozin

Cited by 37 publications

References 2 publications

Prolonged Ketosis in a Patient With Euglycemic Diabetic Ketoacidosis Secondary to Dapagliflozin

Prolonged Ketosis in a Patient With Euglycemic Diabetic Ketoacidosis Secondary to Dapagliflozin

Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Nonglycemic Outcomes in Patients with Type 2 Diabetes

A case series of DKA occurring in patients receiving treatment with SGLT‐2 inhibitors

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