Euglycemic diabetic ketoacidosis: The clinical concern of SGLT2 inhibitors

Benmoussa, Jamila; Clarke, Matthew; Penmetsa, Amulya; Khine, Le Yu; Leykina, Lina; Diaz, Keith; Otterbeck, Philip

doi:10.1016/j.jecr.2016.05.002

Cited by 7 publications

(8 citation statements)

References 14 publications

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“…We retrieved a total of 105 episodes of DKA in patients receiving SGLT2i from May 2014 to April 2017 . Demographic characteristics, type of diabetes and type of SGLT2i are reported in Table .…”

Section: Review Of the Literaturementioning

confidence: 99%

“…We retrieved a total of 105 episodes of DKA in patients receiving SGLT2i from May 2014 to April 2017. [18][19][20][21] Demographic characteristics, type of diabetes and type of SGLT2i are reported in Table 1. Most (62%) episodes occurred in T2D patients, and the most commonly used SGLT2i was canagliflozin ( Figure 1A and B).…”

Section: Case Reportsmentioning

confidence: 99%

“…Indeed, SGLT2i‐associated DKA episodes were sometimes reported to be “euglycaemic” and thereby susceptible to late diagnosis . The risk of DKA is perceived to be higher when SGLT2is are used off‐label for the treatment of T1D, and some reports indicate that SGLT2i‐associated DKA occurred in patients with presumed T2D who were subsequently diagnosed with T1D or latent autoimmune diabetes in the adult (LADA) …”

Section: Introductionmentioning

confidence: 99%

“…17 The risk of DKA is perceived to be higher when SGLT2is are used off-label for the treatment of T1D, and some reports indicate that SGLT2i-associated DKA occurred in patients with presumed T2D who were subsequently diagnosed with T1D or latent autoimmune diabetes in the adult (LADA). [18][19][20][21] The number of reports is steadily increasing, and the exact rate at which this life-threatening AE occurs during SGLT2i therapy is difficult to establish. In this article, we report 2 new cases of SGLT2iassociated DKA and an updated review of the cases reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

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Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: An updated review of the literature

Bonora

Avogaro

Fadini

2017

Diabetes Obesity Metabolism

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Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are increasingly used for the treatment of type 2 diabetes (T2D) and can improve glucose control also in type 1 diabetes (T1D). In May 2015, regulatory agencies issued a warning that SGLT2is may cause diabetic ketoacidosis (DKA). We report details on 2 new cases of SGLT2i-associated DKA and review the literature for similar cases within randomized controlled trials (RCTs), cohort studies and single reports. We searched the medical literature for reports of SGLT2i-associated DKA cases. A quantitative analysis of frequency and clinical characteristics is reported. The 2 narrative cases illustrate that SGLT2i-associated DKA can occur in patients with T1D incorrectly diagnosed as T2D, perhaps without the presence of obvious DKA precipitating factors. The incidence of SGLT2i-associated DKA was less than 1/1000 in randomized controlled trials and 1.6/1000 person-years in cohort studies. We retrieved detailed data on 105 SGLT2i-associated DKA case reports, wherein 35% showed glucose levels of less than 200 mg/dL and 22% were not associated with typical triggers. In case reports and in pharmacovigilance databases, duration of SGLT2i treatment before DKA onset was extremely variable. Fatal SGLT2i-associated DKA episodes were found only in pharmacovigilance databases and represented 1.6% of all reported cases. DKA is a rare adverse event during SGLT2i therapy. Predisposing and precipitating factors are still incompletely understood, although a minority of cases lacked typical DKA triggers. More narrative case series and cohort studies are needed to better understand the true risk and the spectrum of this adverse event.

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Section: Review Of the Literaturementioning

confidence: 99%

Section: Case Reportsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: An updated review of the literature

Bonora

Avogaro

Fadini

2017

Diabetes Obesity Metabolism

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“…The end result of these combined mechanisms is hyperketonemia in the setting of euglycemia [ 9 , 16 ]. Additionally, euDKA associated with SGLT-inhibitors causes twice the amount of renal glucose clearance compared to DKA [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Dapagliflozin-Associated Euglycemic Diabetic Ketoacidosis in a Patient Presenting with Acute Pancreatitis

Badwal

Tariq

Peirce

2018

Case Reports in Endocrinology

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Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a class of medications used for glycemic control in type II diabetes mellitus. Their mechanism of action involves preventing resorption of glucose at the proximal kidney, thereby promoting glucosuria and weight loss. However, they have also been found to be associated with euglycemic diabetic ketoacidosis (euDKA). This case describes a 25-year-old male with a history of type II diabetes on metformin, sitagliptin, and dapagliflozin who was admitted with his third episode of pancreatitis secondary to hypertriglyceridemia. His home oral glycemic agents were continued as inpatient. Despite tight euglycemic control, the patient developed profound metabolic acidosis and was found to have an elevated beta-hydroxybutyrate level and normal lactic acid level. He was admitted into the intensive care unit and started on an insulin drip, and after resolution of his acidosis he was transitioned to basal insulin successfully. He was discharged with an insulin regimen while his oral glycemic agents were discontinued indefinitely. SGLT-2 inhibitors are associated with euDKA, most likely as a result of their non-insulin-dependent glucose clearance, hyperglucagonemia, and decreased ketone clearance. The aim of this case report is to inform the physician about the possibility of euDKA in a patient with type II diabetes on a SGLT-2 inhibitor presenting with an acute illness.

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Canagliflozin

2016

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Euglycemic diabetic ketoacidosis: The clinical concern of SGLT2 inhibitors

Cited by 7 publications

References 14 publications

Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: An updated review of the literature

Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: An updated review of the literature

Dapagliflozin-Associated Euglycemic Diabetic Ketoacidosis in a Patient Presenting with Acute Pancreatitis

Canagliflozin

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