Ketoacidosis Due to Empagliflozin, a Paradigm Shift: Case Report and Review of Literature

2019 ◽  
Vol 15 (4) ◽  
pp. 259-262 ◽  
Author(s):  
Carlos Hernandez-Quiles ◽  
Nieves Ramirez-Duque ◽  
Domingo Acosta-Delgado
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Case Report ◽  
Paradigm Shift ◽  
Cardiovascular Events ◽  
Sglt2 Inhibitors ◽  
Review Of Literature ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Introduction: Sodium-glucose cotransporter 2(SGLT2)-inhibitors are new antihyperglycemic agents that have shown a reduction in cardiovascular events in type 2 diabetes mellitus. Recent warnings have been developed about an increased risk of euglycemic and moderate hyperglycemic diabetic ketoacidosis with the use of SGLT2 inhibitors, but its real incidence is not available yet. Case Report: We present a case of DKA with moderate hyperglycemia in a patient treated with metformin and empagliflozin. Conclusion: DKA in patients treated with SGLT2 inhibitors can be presented as euglycemic and moderated hyperglycemia. This special presentation poses a physician’s challenge.

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

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.

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 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.

Structural Perspectives and Advancement of SGLT2 Inhibitors for the Treatment of Type 2 Diabetes

2021 ◽  
Vol 17 ◽  
Author(s):  
Shivani Sharma ◽  
Amit Mittal ◽  
Shubham Kumar ◽  
Anu Mittal
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cell Function ◽  
Sglt2 Inhibitors ◽  
Health Care Practices ◽  
Sodium Glucose Cotransporter ◽  
Β Cell Function ◽  
Insulin Dependent ◽  
Glycemic Regulation

: Diabetes mellitus is an ailment that affects a large number of individuals worldwide and its pervasiveness has been predicted to increase later on. Every year, billions of dollars are spent globally on diabetes-related health care practices. Contemporary hyperglycemic therapies to rationalize type 2 diabetes mellitus (T2DM) mostly involve pathways that are insulin-dependent and lack effectiveness as the pancreas’ β-cell function declines more significantly. Homeostasis via kidneys emerges as a new and future strategy to minimize T2DM complications. This article covers the reabsorption of glucose mechanism in the kidneys, the functional mechanism of various Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, their structure and driving profile, and a few SGLT2 inhibitors now accessible in the market as well as those in different periods of advancement. The advantages of SGLT2 inhibitors are dose-dependent glycemic regulation changes with a significant reduction both in the concentration of HbA1c and body weight clinically and statistically. A considerable number of SGLT2 inhibitors have been approved by the FDA, while a few others, still in preliminaries, have shown interesting effects.

Risk of volume reduction associated with sodium-glucose cotransporter-2 inhibitors treatment: a meta-analysis of randomized controlled trials

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
X.I Rong ◽  
X Li ◽  
Q Gou ◽  
X.P Chen
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Sglt2 Inhibitors ◽  
Volume Reduction ◽  
Controlled Trials ◽  
Older Individuals ◽  
Osmotic Diuresis ◽  
Sodium Glucose Cotransporter

Abstract Introduction Sodium-glucose cotransporter-2 (SGLT2) inhibitors is a newly class of drug which improving glycemia by enhancing glycosuria, subsequently reducing blood pressure by osmotic diuresis and natriuresis. There are multiple large-scale randomized control trials demonstrating that SGLT2 inhibitors had salutary effect on cardiovascular-renal outcome, especially on heart failure. Although SGLT2 inhibitors exhibited promising potential value on treatment for type 2 diabetes mellitus (T2DM) with cardiovascular-renal comorbidities, the potential adverse events (AEs) related to osmotic diuresis such as volume reduction should not be neglected. Moreover, older individuals, those with moderate renal impairment, and those receiving antihypertensive therapies are susceptible to adverse events related to volume reduction. Purpose To assess the association between sodium-glucose cotransporter-2 inhibitors and risk of volume reduction in patients with type 2 diabetes mellitus. Methods A systematic literature retrieval was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception up to 10 December 2019, Data for study characteristics and outcomes of interest were extracted from each eligible study. Pooled risk ratios (RRs) with 95% confidence interval (CI) for volume reduction was calculated using random-effects model. Result A total of 51 studies (n=56,866) were included in our meta-analysis, with a result of 1,337 incident volume reduction cases (814 in the SGLT2 inhibitors group, 523 in the control group). The pooled RR was 1.15 (95% CI: 1.03–1.28). It is evident that receiving SGLT2 inhibitors had increased the risk of volume reduction, when stratified by placebo-control or active-control the result was consistent. Conclusion Our meta-analysis has demonstrated that SGLT2 inhibitors increase the risk of volume reduction in patients with T2DM. It is necessary to attention for the risk of volume reduction associated with SGLT2 inhibitors, especially in older individuals, those with moderate renal impairment, and those receiving antihypertensive therapies. SGLT2 inhibitors vs control Funding Acknowledgement Type of funding source: None

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