Diabetic Ketoacidosis in Patients with Type 2 Diabetes on Sodium-Glucose Cotransporter-2 Inhibitors - A Case Series

Sharma, Purva; Jobanputra, Yash; Lewin, Karen; Bagatell, Stuart; Lichtstein, Daniel M.

doi:10.2174/1574887113666180314101436

Cited by 16 publications

(11 citation statements)

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“…We utilized the most common definition of DKA – glucose >250 mg/dl, metabolic acidosis and presence of ketones – [13] which may under-report euglycemic DKA [32] . We did not think euglycemic DKA was prevalent in our cohort, especially as the number of patients treated with SGLT-2 inhibitors, a known causal factor for euglycemic DKA [ 33 , 34 ] was trivial. Additionally, because patients were diagnosed with DKA based on multiple criteria (Table S4; see supplementary materials associated with this article on line ), we could not determine if DKA severity variably affected outcomes.…”

Section: Discussionmentioning

confidence: 99%

Diabetic ketoacidosis and mortality in COVID-19 infection

Stevens

Bogun

McMahon

et al. 2021

Diabetes & Metabolism

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Aim - Patients with diabetes have increased morbidity and mortality from COVID-19. Case reports describe patients with simultaneous COVID-19 and diabetic acidosis (DKA), however there is limited data on the prevalence, predictors and outcomes of DKA in these patients. Methods - Patients with COVID-19 were identified from the electronic medical record. DKA was defined by standardized criteria. Proportional hazard regression models were used to determine risk factors for, and mortality from DKA in COVID-19. Results - Of 2366 patients admitted for COVID-19, 157 (6.6%) patients developed DKA, 94% of whom had antecedent type 2 diabetes, 0.6% had antecedent type 1 diabetes, and 5.7% patients had no prior diagnosis of diabetes. Patients with DKA had increased hospital length of stay and in-patient mortality. Higher HbA1c predicted increased risk of incident DKA (HR 1.47 per 1% increase, 95% CI 1.40-1.54). Risk factors for mortality included older age (HR 1.07 per 5 years, 95% CI 1.06 - 1.08) and need for pressors (HR 2.33, 95% CI 1.82-2.98). Glucocorticoid use was protective in patients with and without DKA. Conclusion - The combination of DKA and COVID-19 is associated with greater mortality, driven by older age and COVID-19 severity.

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Section: Discussionmentioning

confidence: 99%

Diabetic ketoacidosis and mortality in COVID-19 infection

Stevens

Bogun

McMahon

et al. 2021

Diabetes & Metabolism

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“…In addition to improved glycemia and modest weight loss, reductions of adverse cardiovascular and renal complications of T2D have been demonstrated with use of SGLT2i in recent clinical trials (8). However, it is now clear that SGLT2i have consistent effects to raise circulating ketone bodies and, in uncommon instances, can precipitate DKA, particularly among insulinopenic patients (9)(10)(11)(12)(13)(14)(15)(16). While the mechanism by which SGLT2i causes ketosis has not been established, patients treated with these agents have elevations in circulating glucagon and increased hepatic glucose production.…”

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confidence: 99%

The Limited Role of Glucagon for Ketogenesis During Fasting or in Response to SGLT2 Inhibition

et al. 2020

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Glucagon is classically described as a counterregulatory hormone that plays an essential role in the protection against hypoglycemia. In addition to its role in the regulation of glucose metabolism, glucagon has been described to promote ketosis in the fasted state. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering drugs that act primarily in the kidney, but some reports have described direct effects of SGLT2i on α-cells to stimulate glucagon secretion. Interestingly, SGLT2 inhibition also results in increased endogenous glucose production and ketone production, features common to glucagon action. Here, we directly test the ketogenic role of glucagon in mice, demonstrating that neither fasting- nor SGLT2i-induced ketosis is altered by interruption of glucagon signaling. Moreover, any effect of glucagon to stimulate ketogenesis is severely limited by its insulinotropic actions. Collectively, our data suggest that fasting-associated ketosis and the ketogenic effects of SGLT2 inhibitors occur almost entirely independent of glucagon.

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“…Interestingly, although the study population comprised patients starting a second-line DM agent, some had underlying comorbidities, including diabetes-related complications, which may have contributed to these poor DM-related outcomes. Sodium-glucose contransporter 2 inhibitors, which in some previous studies have been linked to an increased risk for euglycemic and hyperglycemic diabetic ketoacidosis, 12 , 13 had no difference in overall metabolic complications in our study, which included episodes of diabetic ketoacidosis in the outcome definition. However, because event rates were generally low and the confidence interval for the IRR comparing SGLT-2 inhibitors to SFUs was wide, this finding requires confirmation.…”

Section: Discussionmentioning

confidence: 60%

Glycemic Outcomes of Second-Line Diabetes Drug Choice in a Real-World Population

Wallia

O’Brien

Liss

et al. 2021

Mayo Clinic Proceedings: Innovations, Quality & Outcomes

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Hypoglycemia and acute metabolic complications (AMCs; ketoacidosis, hyperosmolarity, and coma) are glycemic outcomes that have high cost and high morbidity; these outcomes must be taken into consideration when choosing initial second-line therapy after metformin. We conducted a retrospective cohort study analyzing national administrative data from adults with type 2 diabetes mellitus who started a second-line diabetes medication (sulfonylureas [SFUs], thiazolidinediones [TZDs], glucagon-like peptide 1 [GLP-1] agonists, dipeptidyl peptidase 4 [DPP-4] inhibitors, basal insulin, or sodium-glucose contransporter 2 [SGLT-2] inhibitors) between April 1, 2011 and September 30, 2015 (N=43,288) and compared rates of hypoglycemia and AMCs. Most patients (24,506 [56.6%]) were prescribed sulfonylurea as second-line treatment, followed by DPP-4 inhibitors (7953 [18.4%]), GLP-1 agonists (3854 [8.9%]), basal insulin (2542 [5.9%]), SGLT-2 inhibitors (2537 [5.9%), and TZDs (1896 [4.4%]). Baseline rates of hypoglycemia varied more than 5-fold across initial second-line antidiabetic medication classes, and rates of AMCs varied 7-fold. Compared with patients taking an SFU, lower adjusted rates of hypoglycemia were associated with taking a DPP-4 inhibitor (63% lower rate; incidence rate ratio [IRR], 0.37; 95% CI, 0.25 to 0.57), SGLT-2 inhibitor (54% lower; IRR, 0.46; 95% CI, 0.22 to 0.94), or TZD (79% lower; IRR, 0.21; 95% CI, 0.08 to 0.56) but not a glucagon-like peptide 1 agonist or basal insulin. For AMCs, only initiation of a DPP-4 inhibitor (43% lower rate; IRR, 0.57; 95% CI, 0.41 to 0.81) was associated with a lower adjusted rate compared with SFU. Use of SGLT-2 inhibitors was not associated with a substantially increased rate of acute metabolic complications compared with SFU. Special attention still needs to be paid to glycemic outcomes when choosing a second-line diabetes therapy following metformin.

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Diabetic Ketoacidosis in Patients with Type 2 Diabetes on Sodium-Glucose Cotransporter-2 Inhibitors - A Case Series

Cited by 16 publications

References 0 publications

Diabetic ketoacidosis and mortality in COVID-19 infection

Diabetic ketoacidosis and mortality in COVID-19 infection

The Limited Role of Glucagon for Ketogenesis During Fasting or in Response to SGLT2 Inhibition

Glycemic Outcomes of Second-Line Diabetes Drug Choice in a Real-World Population

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