Euglycemic Diabetic Ketoacidosis Associated With Sodium–Glucose Cotransporter Type 2 Inhibitors in Patients With Type 2 Diabetes Mellitus Receiving Oral Therapy

2017 ◽  
Vol 32 (2) ◽  
pp. 240-243 ◽  
Author(s):  
Ryan B. Dull ◽  
Mikayla L. Spangler ◽  
Emily L. Knezevich ◽  
Britney M. Lau
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Ketoacidosis ◽  
Case Reports ◽  
Serious Adverse Events ◽  
Type 2 Dm ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Introduction and Objective: Postmarketing reports and warnings of serious adverse events such as diabetic ketoacidosis (DKA) have raised concern regarding the safety of sodium–glucose cotransporter 2 inhibitors (SGLT2i). This report describes 2 cases of symptomatic SGLT2i-associated euglycemic DKA (euDKA) leading to hospitalization in patients with type 2 diabetes mellitus (DM) previously well controlled on oral medications. Case Reports: Subject 1 is a 55-year-old female admitted with euDKA precipitated by infection and managed with intravenous insulin. This case was notable for a delayed diagnosis of euDKA and lack of clinical improvement despite withholding dapagliflozin. Subject 2 is a 62-year-old male admitted with euDKA precipitated by infection. His clinical condition improved rapidly and euDKA responded to withdrawal of empagliflozin alone. Discussion: Applying the Naranjo adverse medication reaction probability scale to each case (subject 1 score = 3 points; subject 2 score = 4 points) suggests these are possible adverse reactions to SGLT2i. Data from randomized controlled trials suggest DKA events in adults with type 2 DM receiving SGLT2i are rare and similar to placebo. However, data from a large cohort suggest these events occur more frequently and are associated with a 2-fold increased risk of DKA. Conclusion: This class of medications may be associated with a higher real-world risk of DKA in adults with type 2 DM than previously reported. Patients prescribed these medications should receive vigilant assessment for features of traditional DKA as well as euDKA.

Sodium glucose cotransporter-2 inhibitor treatment and the risk of diabetic ketoacidosis in Denmark: A retrospective cohort study of five years of use.

2020 ◽  
Vol 15 ◽  
Author(s):  
Henrik V.B. Laursen ◽  
Johan B. Røikjer ◽  
Jakob Dal ◽  
Morten Hasselstrøm Jensen
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Ketoacidosis ◽  
Retrospective Cohort ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Glucagon Like Peptide 1 ◽  
Cox Proportional Hazard Regression

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been associated with increased risk of diabetic ketoacidosis (DKA) in both people with type 1 and type 2 diabetes mellitus. Too few studies using data from high-quality registries exist, that attempt to determine the real-world impact of the increasing use of this drug. Objective: The aim of this study was to investigate the incidence and risk of DKA in connection with SGLT2i treatment in Denmark between 2013-2017. Method: A nationwide retrospective cohort of people with type 2 diabetes mellitus using SGLT2i or glucagon-like peptide-1 receptor agonists (GLP1-RA) was established and analysed using both Cox-proportional hazard regression and Kaplan-Meier survival analysis. Result: The 37,058 individuals included in the cohort, were made up of SGLT2i (10,923), GLP1-RA (18,849), SGLT2i+insulin (2,069), and GLP1-RA+insulin (10,178) users. The incidence rate (IR) of DKA was 0.84 (95% CI 0.49- 1.44) and 0.53 (95% CI 0.36-0.77) for the SGLT2i and GLP1-RA groups, respectively. There was no statistically significant increase in the risk for DKA with SGLT2i use (HR 1.02, 95% CI, 0.44-2.36). However, for the SGLT2i+insulin and GLP1-RA+insulin groups, IRs were 3.47 (95% CI 1.92-6.27) and 0.97 (95% CI 0.68-1.37) respectively, and the risk was statistically significantly higher (HR 5.42, 95% CI 2.16-13.56). Conclusion: We observed no significant increase in risk of DKA for SGLT2i users compared to GLP1-RA. However, a significantly higher IR of DKA was observed with concomitant insulin use, and the risk of DKA was considerably higher for the SGLT2 group using insulin.

scholarly journals Association between Markers of Fibrosis and Heart Failure Incidence in Patients with Type 2 Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Denis A. Lebedev ◽  
Elena A. Lyasnikova ◽  
Elena Yu. Vasilyeva ◽  
Nikolai P. Likhonosov ◽  
Maria Yu. Sitnikova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Type I ◽  
Procollagen Type ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Type 2 diabetes mellitus (T2DM) and chronic heart failure (HF) have close association, and several biomarkers have been studied to better understand this association and improve prediction of HF in T2DM. Furthermore, in recent clinical trials, sodium glucose cotransporter 2 inhibitors (SGLT2i), glucose-lowering drugs, improved HF outcomes. The objective of the present study was to evaluate association between circulating biomarkers of fibrosis and incidence of HF with preserved ejection fraction (HFpEF) in patients with T2DM receiving sodium glucose cotransporter 2 inhibitors (SGLT2i). Materials and Methods. At baseline, transthoracic echocardiography and laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), soluble suppression of tumorigenesis-2 (sST2), galectin-3 (Gal-3), C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1) were done. After 3 years of follow-up, information about HF events (hospitalization for HF, established HF in outpatient department by a cardiologist) was obtained. Results. Seventy-two patients were included in the study. The mean age was 57 (49.7; 63.2) years; 44% were female. Most patients had T2DM for more than 4 years. All patients were overweight or had obesity, and 93% patients had arterial hypertension (AH). After 3 years of follow-up, HFpEF was established in 21% patients. Patients were divided into two groups according to the presence of HFpEF, and baseline characteristics were compared. Patients with HF were older and had longer diabetes and AH duration and higher Nt-proBNP, Gal-3, PIIINP, and PICP levels at baseline than patients without HF (all p < 0.05 ). Gal − 3 > 10  ng/ml ( OR = 2.25 ; 95% CI, 1.88–5.66; p = 0.01 ) and NT − pro − BNP > 80  pg/ml ( OR = 2.64 ; 95% CI, 1.56–4.44; p = 0.001 ) were associated with increased risk of HF incidence. Age > 60 years, diabetes duration > 10 years, and presence of abdominal obesity were independent predictors of HFpEF as well. Conclusions. T2DM patients treated with SLGT2i, who developed HFpEF after 3 years of follow-up, had higher PICP, PIIINP, Gal-3, and NT-proBNP serum concentrations at baseline, and Gal-3 level was an independent predictor of HFpEF.

scholarly journals High Bodyweight Variability Increases Depression Risk in Patients With Type 2 Diabetes Mellitus: A Nationwide Cohort Study in Korea

2021 ◽  
Vol 12 ◽  
Author(s):  
Ji Hyun An ◽  
Kyung-do Han ◽  
Jin-Hyung Jung ◽  
Juhwan Yoo ◽  
Maurizio Fava ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Obese Patients ◽  
Type 2 Dm ◽  
Increased Risk ◽  
Quartile Group ◽  
New Onset

Objectives: Although obesity is associated with increased risk for depression in patients with type 2 diabetes mellitus (DM), the relationship between body weight variability (BWV) and depression remains poorly studied. This study was to investigate the incidence of depression in patients with type 2 DM according to their BWV.Methods: Intraindividual variation in body weight were measured in the nationwide, population-based retrospective cohort of 540,293 patients with type 2 DM from the Korean national health insurance system between 2009 and 2010. The diagnoses of new-onset depression occurring until the end of 2017 were ascertained. Risk of new-onset depression was examined using multivariate-adjusted Cox proportional hazards regression analysis by BWV quartile.Results: 93,149 (17.2%) patients developed new-onset depression for the follow up. BWV was significantly associated with an increased risk of depression after adjusting for confounding factors. The highest BWV quartile group had a hazard ratio (HR) of 1.17 (95% CI 1.15–1.19) compared to the lowest BWV quartile group as a reference. Obese patients in the highest BWV quartile group showed 12% increased risk of depression (HR 1.12, 95% CI 1.09–1.15) while non-obese patients in the highest BWV quartile group showed 20% increased risk of depression (HR: 1.20, 95% CI: 1.17–1.23) compared to their respective lowest BWV quartile groups.Conclusion: A higher BWV was significantly associated with an increased risk of depression in patients with type 2 DM. Thus, BWV may serve as an indicator for early detection of depression in type 2 DM patients.

scholarly journals The Role of Combined SGLT1/SGLT2 Inhibition in Reducing the Incidence of Stroke and Myocardial Infarction in Patients with Type 2 Diabetes Mellitus

2021 ◽  
Author(s):  
Bertram Pitt ◽  
Gabriel Steg ◽  
Lawrence A. Leiter ◽  
Deepak L. Bhatt
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Relative Increase ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Sglt2 Inhibition

Abstract Purpose In patients with type 2 diabetes mellitus (T2DM), both sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide receptor agonists (GLP-1 RAs) have demonstrated significant improvements in cardiovascular and kidney outcomes independent of their glycemic benefits. This paper will briefly compare the effect of SGLT2is and GLP-1 RAs to that of the SGLT1/2 inhibitor sotagliflozin on the incidence of myocardial infarction (MI) and stroke in patients with T2DM and further postulate mechanisms to account for these findings. Methods and Results Thus far, the results from SCORED and SOLOIST (trials studying the SGLT1/2 inhibitor sotagliflozin) suggest that an increase in SGLT1 inhibition when added to SGLT2 inhibition may contribute to reductions in MI and stroke in patients with T2DM. This benefit is beyond what SGLT2is alone can accomplish and at least similar to GLP-1 RAs but with the added benefit of a reduction in hospitalizations and urgent visits for HF. Larger and longer studies are required to confirm the effectiveness of SGLT1/SGLT2 inhibition in reducing MI and stroke in patients with T2DM and elucidate the mechanisms associated with this finding. Conclusions The role of SGLT1/2 inhibition as an addition to GLP-1 RAs in patients with and without T2DM at increased risk for MI and stroke requires further study. Regardless, the finding that a relative increase in SGLT1/2 inhibition reduces the risk of MI and stroke as well as hospitalizations and urgent visits for heart failure could improve quality of life and reduce the healthcare burden associated with T2DM.

scholarly journals Cholesterol levels and development of cardiovascular disease in Koreans with type 2 diabetes mellitus and without pre-existing cardiovascular disease

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Mee Kyoung Kim ◽  
Kyungdo Han ◽  
Han Na Joung ◽  
Ki-Hyun Baek ◽  
Ki-Ho Song ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 2 Diabetes Mellitus ◽  
Cox Regression ◽  
Reference Group ◽  
Density Lipoprotein ◽  
Type 2 Dm ◽  
Increased Risk

Abstract Background The aim of the present study was to identify a threshold for the cholesterol level at which the risk of cardiovascular disease (CVD) begins to increase in people with type 2 diabetes mellitus (DM). Methods Using the Korean National Health Insurance Service database, 2,077,135 people aged ≥ 40 years with type 2 DM who underwent regular health checks between 2009 and 2012 were included. Subjects with previous CVD were excluded. Cox regression analyses were performed to estimate the risk of CVD for each low-density lipoprotein cholesterol (LDL-C) group using the < 70 mg/dL as the reference group. Results There were 78,560 cases of stroke (3.91%), and 50,791 myocardial infarction (MI, 2.53%) during a median follow-up of 7.1 years. Among participants not taking statins, LDL-C levels of 130–159 mg/dL and ≥ 160 mg/dL were significantly associated with the risk of MI: the hazard ratios (HRs) (95% confidence interval) were 1.19 (1.14–1.25) and 1.53 (1.46–1.62), respectively. Among participants taking statins, all categories of LDL-C level ≥ 70 mg/dL were significantly associated with increased risk of stroke and MI. Conclusions We identified an increased risk of CVD in people with an LDL-C level ≥ 130 mg/dL among individuals with type 2 DM not taking statins. The risk of CVD was significantly higher in those taking statins with an LDL-C level ≥ 70 mg/dL.

scholarly journals Sodium–glucose cotransporter 2 inhibitor-induced euglycemic diabetic ketoacidosis in a patient with coronavirus disease 2019: a case report

2022 ◽  
Vol 16 (1) ◽  
Author(s):  
Edwin Sze Sian Yii ◽  
Athirah Wan Azli ◽  
Premela Naidu Sitaram
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Ketoacidosis ◽  
Oral Antihyperglycemic Agents ◽  
Intravenous Insulin ◽  
Sodium Glucose Cotransporter ◽  
High Index Of Suspicion ◽  
Euglycemic Diabetic Ketoacidosis

Abstract Background Sodium–glucose cotransporter 2 inhibitors are among the new-generation oral antihyperglycemic agents that have been used in the treatment of type 2 diabetes mellitus. With the recent coronavirus disease 2019 pandemic and rise of cases in the third wave, diagnosis of life-threatening euglycemic diabetic ketoacidosis may easily be overlooked or missed. Case presentation We present the case of a 37-year-old Malay gentleman with underlying type 2 diabetes mellitus on empagliflozin, who presented to our hospital with symptomatic coronavirus disease 2019 infection and diabetic ketoacidosis. He developed severe rebound euglycemic diabetic ketoacidosis due to the continuous usage of empagliflozin for glycemic control alongside intravenous insulin. Conclusions Physicians should have a high index of suspicion in diagnosing and managing euglycemic diabetic ketoacidosis, including withholding treatment of sodium–glucose cotransporter 2 inhibitors during the acute management of diabetic ketoacidosis.

scholarly journals P44 Type 2 diabetes mellitus in children: non-insulin medication, where are we up to?

2019 ◽  
Vol 104 (6) ◽  
pp. e35.2-e35
Author(s):  
R Austin ◽  
P Paul ◽  
D Hawcutt
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Case Reports ◽  
Health Concern ◽  
Current Evidence ◽  
Increased Risk ◽  
Dipeptidyl Peptidase 4 Inhibitors

BackgroundChildhood type 2 diabetes mellitus (T2DM) is a relatively rare condition but is an important health concern as its prevalence continues to rise. Current management consists of lifestyle modification, metformin and insulin. Several new pharmacological classes are currently used in adult medicine but are not yet available in paediatric care.In this review we will look at the current evidence for use of these newer medications in the paediatric population.MethodsA literature search (EMBASE, Medline, Pubmed, CINHAL) was performed for papers studying the use of non-insulin medications in children; including a separate search of ´clinicaltrials.gov´ to identify any ongoing trials in paediatric T2DM.ResultsNewer classes of medications include incretin mimetics, dipeptidyl peptidase-4-inhibitors, sodium/glucose-cotransporter-2-inhibitors, and thiazolidinediones. There have been a small number of pharmacokinetic/pharmacodynamic studies carried out in small cohorts of paediatric participants, but larger long-term efficacy and safety trials are lacking. These studies and individual case-reports have shown good tolerability but are unable to identify any long-term effects associated with these medications.Randomised controlled trials studying rosiglitazone and glimepiride use in children have been performed. However, safety concerns in adults and notable side-effects including weight gain, mean their future use is uncertain.Currently many relevant trials involving paediatric patients listed on ´clinicaltrials.gov´ are awaiting completion.ConclusionMedical management for T2DM in children remains limited. Ongoing studies are aiming to equip practitioners with wider treatment options in the future. However, there are concerns regarding the long-term safety of these medications due to the increased risk of pancreatitis, gallbladder conditions and bladder malignancy in adult patients.Paediatric T2DM patients suffer from complications earlier and more severely compared with adults, making this is a pressing issue. Long-term surveillance studies to identify adverse effects and a framework for highlighting research gaps are required to enable improvements in paediatric T2DM management.Disclosure(s)Nothing to disclose

scholarly journals Plasma Atherogenic Index in Type 2 Diabetes Mellitus Patients

2020 ◽  
Vol 15 (2) ◽  
pp. 204-205
Author(s):  
Most. Sarmin Sultana ◽  
Yasmin Akhter ◽  
Mimi Parvin ◽  
Lubna Naznin ◽  
Md Mahbub Ul Alam ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Personal Data ◽  
Armed Forces ◽  
Atherogenic Index ◽  
Cross Sectional ◽  
Type 2 Dm ◽  
Increased Risk

Introduction:Atherogenic index of plasma (AIP) is defined as log of TG to HDL-C ratio. People with high AIP have a higher risk for coronary heart disease (CHD) than those with low AIP. AIP is useful in predicting atherogenecity. Objectives:  To determination of AIP among the study subjects and find out the prevalence of AIP among type 2 diabetes mellitus (DM) patients. Materials and Methods: This cross sectional study was conducted at Armed Forces Institute of Pathology (AFIP) from November 2014 to October 2015. The study included 300 type 2 DM patients belonging to the age group 30-60 years. Fasting plasma glucose (FPG), HDL-C, TG were estimated. The AIP was calculated as log (TG/HDL-C) using the Czech online calculatorof atherogenic risk. Personal data and history of co-existing medical conditions were collected by data collection sheet. Data were analyzed by SPSS version 18.0. Results: Among 300 study subjects the AIP were found in the range of “increased risk” in 298(99.3%) and “low risk” in 02(0.7%). In this study mean FPG was 9.81±3.08 mmol/L and mean AIP was 0.73 ± 0.23A and significant positive correlation between FPG and AIP (r = 0.123, p < 0.05) was observed. Conclusion: The study revealed that AIP is significantly higher in type 2 DM patients. So, patients with type 2 DM should be followed up with AIP regularly. JAFMC Bangladesh. Vol 15, No 2 (December) 2019: 204-205

Evolving Evidence of Diabetic Ketoacidosis in Patients Taking Sodium-Glucose Cotransporter 2 Inhibitors

2020 ◽  
Vol 105 (8) ◽  
pp. 2475-2486 ◽  
Author(s):  
Nicola Fleming ◽  
Peter Shane Hamblin ◽  
David Story ◽  
Elif I Ekinci
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Diabetic Ketoacidosis ◽  
Case Reports ◽  
Significant Risk ◽  
Hormonal Changes ◽  
Precipitating Factors ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Abstract Introduction Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as an important class of blood glucose–lowering medications, due to cardiovascular, metabolic, and renal benefits. However, there is a small but significant risk of diabetic ketoacidosis (DKA) associated with their use. Methods A literature search was conducted in Ovid MEDLINE and Embase to July 2019 using variants on the key search terms sodium-glucose cotransporter 2, diabetic ketoacidosis, and type 2 diabetes. A broad spectrum of evidence was incorporated to facilitate a comprehensive narrative review. Further sources were identified through hand searching of reference lists. Discussion Although cardiovascular outcome trials demonstrated mixed evidence of SGLT2i associated DKA, increasing evidence from case reports and cohort studies has identified an increased risk. SGLT2i use is associated with a ketotic state caused by an increased glucagon:insulin ratio and stimulated by factors including stress-induced hormonal changes, insufficient insulin, decreased glucose, increased ketone resorption, and hypovolemia. Atypical presentations of DKA with lower-than-expected blood glucose levels are possible with SGLT2i use, so clinical and biochemical monitoring is vital for early identification and management. DKA risk is particularly increased with precipitating factors, therefore optimization of risk factors is vital. Recommendations for perioperative and sick day management of patients taking SGLT2i have been suggested based on available evidence. Conclusion SGLT2i are an excellent class of drug in the physician’s toolkit for managing type 2 diabetes. However, both clinicians and patients must be aware of the potential for DKA and the need for increased monitoring, both clinically and biochemically, when potential precipitating factors are present. In acutely unwell patients, these medications should be withheld to reduce the risk of DKA.

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