Sodium-glucose cotransporter 2 inhibitor-associated perioperative ketoacidosis: a systematic review of case reports

Seki, Hiroyuki; Ideno, Satoshi; Shiga, Toshiya; Watanabe, Hidenobu; Ono, Midori; Motoyasu, Akira; Noguchi, Hikari; Kondo, Kazuya; Yoshikawa, Takahiro; Hoshijima, Hiroshi; Hyuga, Shunsuke; Shishii, Miho; Nagai, Ai; Higashi, M; Ouchi, Takashi; Yasuda, Kazuki; Kuratani, Norifumi

doi:10.1007/s00540-023-03174-8

Cited by 11 publications

(3 citation statements)

References 79 publications

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“…The proposed mechanism is thought to be based on SGLT-2i activating glucagon and counterregulatory hormones, leading to lipolysis and ketosis, and ultimately establishing an anion gap metabolic acidosis, which then triggers DKA [43]. Preoperative cessation of canagliflozin, dapagliflozin, and empagliflozin should start three days before surgery, while ertugliflozin should begin four days prior due to the elevated risk of DKA during this time period [44]. SGLT-2i support blood pressure management without provoking hypotension [45].…”

Section: Safetymentioning

confidence: 99%

Exploring SGLT-2 Inhibitors: Benefits beyond the Glucose-Lowering Effect—What Is New in 2023?

Young,

Farnoudi,

Chen

et al. 2023

Endocrines

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Sodium-glucose cotransporter-2 (SGLT-2) inhibitors were once known as a class of glycemic-lowering agents to treat type 2 diabetes. As the evolving evidence from recent cardiorenal trials on these agents has shown—e.g., EMPA-REG OUTCOME, DECLARE-TIMI 58, CANVAS Program, DAPA-CKD—disclosing their benefits beyond glycemic management, SGLT-2 inhibitors have stimulated a shift in the management of T2DM and its comorbidities, specifically preventing cardiovascular events in people with ASCVD, preventing heart failure hospitalizations, and delaying the progression of chronic kidney disease. As a result, their usage beyond glycemic management has been included in clinical practice guidelines. Although SGLT-2 inhibitors have shown promising results in cardiorenal outcomes, patients have not had equal access to these agents, at least in the United States, suggesting a systemic issue of health inequity. This review article explores the mechanisms by which cardiorenal benefits are offered, the results of the landmark clinical trials for these agents, and their place in therapy.

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Section: Safetymentioning

confidence: 99%

Exploring SGLT-2 Inhibitors: Benefits beyond the Glucose-Lowering Effect—What Is New in 2023?

Young,

Farnoudi,

Chen

et al. 2023

Endocrines

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“…Despite several attempts to prevent CSA-AKI with a variety of pharmacological interventions, no effective mitigation strategies have been developed to date (2,8,9). Sodium-glucose transporter-2 (SGLT2) inhibitors have been reported to prevent AKI in large cardiovascular and kidney outcome trials in patients with or without type 2 diabetes (T2D) (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

SGLT2 inhibition reduces cardiac surgery-associated acute kidney injury: An open-label randomized study.

Snel,

Oosterom-Eijmael,

Rampanelli

et al. 2024

Preprint

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Background Currently, no effective preventative strategies exist to mitigate Cardiac surgery-associated acute kidney injury CSA-AKI. Sodium-glucose transporter-2 (SGLT2) inhibitors reduced acute kidney injury (AKI) incidence in large, randomized placebo-controlled outcome trials. We hypothesized that perioperative SGLT2 inhibition could also reduce CSA-AKI. Methods In this open-label phase IV, randomized, parallel-group, pilot study, adult patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomized to receive either daily an SGLT2 inhibitor, (empagliflozin (10 mg; oral)) from three days prior to surgery until postoperative day two or standard-of-care. Serum and urine biomarkers for acute kidney injury were measured, including NGAL, KIM-1, and HIF-1 α . Additional outcomes included AKI incidence according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria as well as metabolic parameters, including ketone body concentrations and glycemic control. Results Between March 2022 and April 2023, 55 patients were included (sex: 73% male, age: 66 ± 10 years, BMI: 28 ± 4 kg/m2, empagliflozin n = 25, control n = 30) in the intention-to-treat analysis. Empagliflozin significantly reduced the incidence of CSA-AKI (20% vs 66.7%; absolute difference 46.7%, 95% CI, -69.7 – -23.6; P=.001). Following surgery, NGAL, and KIM-1 were found to increase in both arms, whereas a significant increment in serum HIF-1α after surgery was solely observed in the control group. We observed no between-group differences in the incidence of (euglycemic) ketoacidosis or hypoglycemic events. Conclusions Perioperative SGLT2 inhibition, compared with standard of care, significantly reduced the incidence of CSA-AKI. These findings warrant validation in large-scale, double-blind, placebo-controlled, randomized trials

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“…Currently, reports on SGLT2-related euglycemic ketoacidosis in patients without diabetes are limited [5][6][7]. Because physiologic stress-induced changes due to surgery in addition to fasting increase the risk of ketoacidosis through the release of catecholamines, cortisol production, and decreased insulin secretion and utilization [8], perioperative withdrawal of SGLT2 inhibitors is recommended in patients with or without diabetes before undergoing surgery [9].…”

Section: Introductionmentioning

confidence: 99%

Euglycemic Ketoacidosis in a Patient without Diabetes Taking Sodium-Glucose Cotransporter 2 Inhibitors for Heart Failure

Miyazaki,

Nakano,

Takahashi

et al. 2024

Am J Case Rep

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Rare coexistence of disease or pathology Background:Sodium-glucose cotransporter 2 (SGLT2) inhibitors are used to improve the prognosis of patients with diabetes, heart failure, or chronic kidney disease. The use of SGLT2 inhibitors in patients without diabetes is expected to increase. Diabetic ketoacidosis is a severe complication of SGLT2 inhibitors in patients with diabetes.People without diabetes are thought to be less likely to develop ketoacidosis, and reports of SGLT2 inhibitorinduced ketoacidosis are uncommon in people without diabetes. Case Report:Herein, we describe a case of ketoacidosis in an 83-year-old Japanese woman without diabetes who was administered SGLT2 inhibitors for heart failure (ejection fraction: approximately 30%). Two weeks prior to admission, she had suffered a vertebral fracture and rib fracture due to a fall, which was followed by anorexia, but she continued to take SGLT2 inhibitors. On admission, blood test results revealed a blood glucose level of 124 mg/dL, hemoglobin A1C level of 5.9%, pH of 7.329, HCO 3 concentration of 14.3 mmol/L, and a b-hydroxybutyrate concentration of 5150 μmol/L, leading to a diagnosis of euglycemic ketoacidosis. The patient's C-peptide level was consistent with the blood glucose levels on admission, indicating that she had adequate insulin secretion. The patient was treated only with glucose administration without insulin and was discharged after discontinuation of the SGLT2 inhibitor. Conclusions:This case illustrates that patients with or without diabetes may develop SGLT2 inhibitor-related ketoacidosis after several days of inadequate food intake; therefore, patients should be informed of this risk.

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Sodium-glucose cotransporter 2 inhibitor-associated perioperative ketoacidosis: a systematic review of case reports

Cited by 11 publications

References 79 publications

Exploring SGLT-2 Inhibitors: Benefits beyond the Glucose-Lowering Effect—What Is New in 2023?

Exploring SGLT-2 Inhibitors: Benefits beyond the Glucose-Lowering Effect—What Is New in 2023?

SGLT2 inhibition reduces cardiac surgery-associated acute kidney injury: An open-label randomized study.

Euglycemic Ketoacidosis in a Patient without Diabetes Taking Sodium-Glucose Cotransporter 2 Inhibitors for Heart Failure

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