SGLT2 Inhibitor–associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis

Goldenberg, Ronald; Berard, Lori; Cheng, Alice; Gilbert, Jeremy; Verma, Subodh; Woo, Vincent; Yale, Jean‐François

doi:10.1016/j.clinthera.2016.11.002

Cited by 227 publications

(229 citation statements)

References 39 publications

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“…8 The debate, however, continues over whether SGLT-2i are actually causative for DKA in the setting of T2DM. 12 In a meta-analysis by Tang et al, in a total of ten eligible RCTs involving 13,134 patients, only 14 DKA events in T2DM patients associated with SGLT-2i use were identified. Overall, the event rates were 0.1% in the group of SGLT-2i users vs 0.06% in the other glucoselowering groups (odds ratio [OR], 1.71; 95% confidence interval [CI], 0.56 to 5.2), with subgroup analyses showing that SGLT-2i were not significantly associated with an increased risk of DKA when compared with placebo (OR, 1.98; 95% CI, 0.56 to 6.9).…”

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confidence: 99%

“…14 While it seems reasonable to propose recommendations around perioperative use of SGLT-2i based on pharmacokinetics as proposed by Lau et al, there is a noteworthy lack of consensus recommendations from major diabetes, surgical, or anesthesia associations for perioperative use of SGLT-2i, which we recently highlighted elsewhere. 15 Although the American Association of Clinical Endocrinologists and the American College of Endocrinology recommend discontinuation of SGLT-2i 24 hr preoperatively, 16 the case series by Lau et al (and others) 8,12 emphasizes that euDKA can still precipitate despite 48 hr perioperative discontinuation of SGLT-2i. 12 This highlights an important clinical knowledge gap around SGLT-2i use in the perioperative setting and represents an opportunity for quality improvement research.…”

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confidence: 99%

“…15 Although the American Association of Clinical Endocrinologists and the American College of Endocrinology recommend discontinuation of SGLT-2i 24 hr preoperatively, 16 the case series by Lau et al (and others) 8,12 emphasizes that euDKA can still precipitate despite 48 hr perioperative discontinuation of SGLT-2i. 12 This highlights an important clinical knowledge gap around SGLT-2i use in the perioperative setting and represents an opportunity for quality improvement research.…”

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confidence: 99%

“…8 Le débat continue toutefois de faire rage quant à savoir si les SGLT-2i sont véritablement la cause de l'acidocétose diabétique dans un contexte de diabète de type 2. 12 Dans une méta-analyse par Tang 14 Alors qu'il semble raisonnable de proposer des recommandations pour l'utilisation périopératoire des SGLT-2i en se fondant sur leur pharmacocinétique, comme le propose Lau et coll., l'absence de recommandations consensuelles provenant d'associations majeures de diabète, de chirurgie ou d'anesthésie pour l'utilisation périopératoire des SGLT-2i est notable, ce que nous avons récemment souligné ailleurs. 15 Bien que l'American Association of Clinical Endocrinologists et l'American College of Endocrinology recommandent d'interrompre les SGLT-2i 24 h avant l'opération, 16 la série de cas de Lau et coll.…”

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“…15 Bien que l'American Association of Clinical Endocrinologists et l'American College of Endocrinology recommandent d'interrompre les SGLT-2i 24 h avant l'opération, 16 la série de cas de Lau et coll. (et d'autres) 8,12 soulignent que l'acidocétose diabétique euglycémique peut tout de même être précipitée malgré une interruption périopératoire de 48 h des SGLT-2i. 12 Ceci met en exergue des lacunes importantes dans les connaissances cliniques entourant l'utilisation des SGLT-2i en période périopératoire et représente une occasion de réaliser des recherches d'amélioration de la qualité.…”

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Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present -'D', either elevated blood glucose levels or a family history of diabetes mellitus; 'K', the presence of high urinary or blood ketoacids; and 'A', a high anion gap metabolic acidosis. Early diagnosis and management is paramount to improve patient outcome. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with an appreciable, although largely preventable morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA, as well as we provide practical recommendations for management of DKA in adults and children. [H1] IntroductionDiabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. DKA is the consequence of an absolute (that is, total absence of) or relative (that is, levels insufficient to supress ketone production) lack of insulin and concomitant elevation of counter-regulatory hormones, usually resulting in the triad of hyperglycaemia, metabolic acidosis and ketosis (elevated levels of ketones in the blood or urine; serum ketone concentration of >3.0mmol/l), often accompanied by varying degrees of circulatory volume depletion [G]. DKA occurs mostly in people with uncontrolled type 1 diabetes mellitus (T1DM, which results from the autoimmune destruction of the β-cells of the islets of Langerhans), but can also occur in adults with poorly controlled type 2 diabetes mellitus (T2DM, a result of impaired insulin secretion or action) under stressful conditions such as acute medical or surgical illnesses and, in adolescents, new onset T2DM (also known as ketosis-prone T2DM) (Figure 1). Although any illness or physiological stress can precipitate DKA, the most frequent causes are infections, particularly urinary tract infections and gastroenteritis 1,2 . DKA was previously considered to be a key clinical feature of T1DM, but has been documented in children and adults with newly diagnosed T2DM 2,3 . Although ketosis-prone T2DM can occur in all populations, epidemiological data suggest that people of African or Hispanic origin seem to be at greater risk 2 . This predisposition likely has a genetic component, but this has yet to be elucidated. Most often individuals with ketosis-prone T2DM have obesity and a strong family history of T2DM and evidence of insulin resistance. Despite presenting with DKA and decreased insulin concentrations, on immunological testing these individuals have the same frequency of the typical autoimmune markers of T1DM such as islet cell, insulin, glutamic acid decarboxylase, and protein tyrosine phosphatase autoantibodies as those who present with HHS and their β-cell function recovers with restoration of insulin secretion quickly after trea...

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Euglycemic diabetic ketoacidosis in association with dapagliflozin use after gastric sleeve surgery in a patient with type II diabetes mellitus

Banakh

Kung

Gupta

et al. 2019

Clinical Case Reports

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Key Clinical Message Sodium–glucose cotransporter 2 inhibitors (SGLT2Is) can be associated with euglycemic diabetic ketoacidosis (eDKA). Severe metabolic acidosis with extreme electrolyte abnormalities can occur with nonsignificant blood glucose elevations in SGLT2I‐treated patients. Additional risk factors for eDKA include prolonged fasting, major illness, large weight loss, and reductions in insulin doses.

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SGLT2 Inhibitor–associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis

Cited by 227 publications

References 39 publications

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in the perioperative setting

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in the perioperative setting

Diabetic Ketoacidosis ¹

Euglycemic diabetic ketoacidosis in association with dapagliflozin use after gastric sleeve surgery in a patient with type II diabetes mellitus

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SGLT2 Inhibitor–associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis

Cited by 227 publications

References 39 publications

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in the perioperative setting

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in the perioperative setting

Diabetic Ketoacidosis 1

Euglycemic diabetic ketoacidosis in association with dapagliflozin use after gastric sleeve surgery in a patient with type II diabetes mellitus

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Diabetic Ketoacidosis ¹