Sodium glucose co-transporter-2 inhibitors (SGLT-2i) are increasingly being used among hospitalized patients. Our objective was to assess the risk of diabetic ketoacidosis (DKA) among hospitalized ...patients receiving an SGLT-2i.
We conducted a multicentre cohort study of patients hospitalized at 19 hospitals. We included patients over 18 years of age who received an SGLT-2i or a dipeptidyl peptidase-4 inhibitor (DPP-4i) in hospital. The primary outcome was the risk of DKA during their hospitalization.
61,517 patients received a DPP-4i and 11,061 received an SGLT-2i. The risk of inpatient DKA was 0.07 % (N = 41 events) among adults who received a DPP-4i and 0.18 % (N = 20 events) among adults who received an SGLT-2i; adjusted odds ratio of 3.30 (95 % CI: 1.85–5.72).
In hospitalized patients, the absolute risk of DKA was 0.2 %, which corresponded to a three-fold higher relative risk.
•We conducted a multicentre cohort study of hospitalized adults to examine the risk of diabetic ketoacidosis (DKA) among patients who received an SGLT2 inhibitor in hospital (SGLT-2i).•The absolute risk of DKA with SGLT-2i was 0.2%, results consistent with a recent meta-analysis of SGLT-2i use in the outpatient setting.
SGLT2 inhibitors have an insulin-independent mechanism of action leading to increasing glycosuria and lowering plasma glucose concentration, which results in cardiovascular and renal benefits shown ...in various studies. Other benefits include improvements in hyperglycemia, decreased fluid retention, reduced weight gain, lower blood pressure, and decreased risk of hypoglycemia. SGLT2 inhibitors produce cardioprotective and renoprotective benefits by inducing a state of Fasting Mimicry. It is therefore noteworthy that SGLT2 inhibitors induce a transcriptional paradigm that closely mimics the cellular response to starvation. These drugs activate SIRT1/AMPK and suppress Akt/mTOR signaling and, consequently, they can promote autophagy, independent of their effects on glucose or insulin. SGLT2 inhibitors regulate the expression of MicroRNA and prevent the occurrence and development of atherosclerosis, and can improve blood vessel stiffness and aging.
Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors), known as flozins, are a recent class of medications gaining recognition for their effectiveness in diabetes, cardiovascular ...health, and heart failure management. The objective of this study is to examine and integrate recent literature concerning the mechanisms, effectiveness, and safety of SGLT2 inhibitors in managing heart failure. Material and Methods of Research: A literature review focused on keywords related to the topic was performed using databases such as PubMed and Google Scholar. Results: SGLT-2 inhibitors, initially developed for type 2 diabetes, significantly benefit heart failure (HF) with reduced, mildly reduced, and preserved ejection fractions by improving various cardiac outcomes. These drugs lower glucose levels and promote osmotic diuresis, natriuresis, and favorable metabolic effects, reducing cardiac preload and afterload. Consequently, SGLT-2 inhibitors are now pivotal in HF treatment, enhancing cardiac efficiency and reducing HF-related hospitalizations and mortality. Conclusion: SGLT-2 inhibitors substantially decrease cardiovascular risk and hospitalizations for heart failure in patients with or without type 2 diabetes, making them crucial in HF management. Consequently, SGLT-2 inhibitors should be considered first-line therapy for heart failure, regardless of concurrent medications, due to their efficacy and comprehensive benefits in managing this condition.
BACKGROUND:Atrial fibrillation (AF) and atrial flutter (AFL) are associated with both diabetes mellitus and its related comorbidities, including hypertension, obesity, and heart failure (HF). SGLT2 ...(sodium-glucose cotransporter 2) inhibitors have been shown to lower blood pressure, reduce weight, have salutary effects on left ventricular remodeling, and reduce hospitalization for HF and cardiovascular death in patients with type 2 diabetes mellitus. We therefore investigated whether SGLT2 inhibitors could also reduce the risk of AF/AFL.
METHODS:DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58) studied the efficacy and safety of the SGLT2 inhibitor dapagliflozin versus placebo in 17 160 patients with type 2 diabetes mellitus and either multiple risk factors for atherosclerotic cardiovascular disease (n=10 186) or known atherosclerotic cardiovascular disease (n=6974). We explored the effect of dapagliflozin on the first and total number of AF/AFL events in patients with (n=1116) and without prevalent AF/AFL using Cox and negative binomial models, respectively. AF/AFL events were identified by search of the safety database using MedDRA preferred terms (“atrial fibrillation,” “atrial flutter”).
RESULTS:Dapagliflozin reduced the risk of AF/AFL events by 19% (264 versus 325 events; 7.8 versus 9.6 events per 1000 patient-years; hazard ratio HR, 0.81 95% CI, 0.68–0.95; P=0.009). The reduction in AF/AFL events was consistent regardless of presence or absence of a history of AF/AFL at baseline (previous AF/AFLHR, 0.79 95% CI, 0.58–1.09; no AF/AFLHR, 0.81 95% CI, 0.67–0.98; P for interaction 0.89). Similarly, presence of atherosclerotic cardiovascular disease (HR, 0.83 95% CI, 0.66–1.04) versus multiple risk factors (HR, 0.78 95% CI, 0.62–0.99; P for interaction 0.72) or a history of HF (HFHR, 0.78 95% CI, 0.55–1.11; No HFHR, 0.81 95% CI, 0.68–0.97; P for interaction 0.88) did not modify the reduction in AF/AFL events observed with dapagliflozin. Moreover, there was no effect modification by sex, history of ischemic stroke, glycated hemoglobin A1c, body mass index, blood pressure, or estimated glomerular filtration rate (all P for interaction >0.20). Dapagliflozin also reduced the total number (first and recurrent) of AF/AFL events (337 versus 432; incidence rate ratio, 0.77 95% CI, 0.64–0.92; P=0.005).
CONCLUSIONS:Dapagliflozin decreased the incidence of reported episodes of AF/AFL adverse events in high-risk patients with type 2 diabetes mellitus. This effect was consistent regardless of the patient’s previous history of AF, atherosclerotic cardiovascular disease, or HF.
REGISTRATION:URLhttps://www.clinicaltrials.gov; Unique identifierNCT01730534.
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are known to increase the risk of euglycemic diabetic ketoacidosis (DKA). Hyperglycemic DKA (hDKA), however, is not a common side effect of SGLT-2 ...inhibitor monotherapy.
We present a case of hyperglycemic DKA in a middle-aged Caucasian male with a history of type 2 diabetes on monotherapy with an SGLT-2 inhibitor, no history of insulin deficiency or evidence of autoimmune diabetes and no precipitating factors for DKA at presentation. The patient was discharged from the hospital on insulin therapy after resolution of DKA and was transitioned to an oral anti-hyperglycemic regimen which did not include SGLT-2 inhibitors. Close outpatient follow up subsequently revealed declining C-peptide levels and increasing hemoglobin A1C levels without any episodes of DKA.
The mechanisms by which SGLT-2 inhibitors cause hDKA are not fully understood and likely involve hyperglucagonemia. Inhibition of SGLT-2 by dapagliflozin has been shown to paradoxically trigger glucagon secretion at higher glucose concentrations possibly due to direct effects on KATP channel activation and membrane depolarization in pancreatic α-cells.
We conclude that monotherapy with SGLT-2 inhibitors presents a risk of not just euglycemic, but also hyperglycemic diabetic ketoacidosis in patients with type 2 diabetes and declining endogenous insulin production.
Diabetes mellitus currently affects over 350 million patients worldwide and is associated with many deaths from cardiovascular complications. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a ...novel class of antidiabetic drugs with cardiovascular benefits beyond other antidiabetic drugs. In the EMPA-REG OUTCOME trial, empagliflozin significantly decreases the mortality rate from cardiovascular causes 38% relative risk reduction (RRR), the mortality rate from all-causes (32% RRR) and the rate of heart failure hospitalization (35% RRR) in diabetic patients with established cardiovascular diseases. The possible mechanisms of SGLT-2 inhibitors are proposed to be systemic effects by hemodynamic and metabolic actions. However, the direct mechanisms are not fully understood. In this review, reports concerning the effects of SGLT-2 inhibitors in models of diabetic cardiomyopathy, heart failure and myocardial ischemia from in vitro, in vivo as well as clinical reports are comprehensively summarized and discussed. By current evidences, it may be concluded that the direct effects of SGLT-2 inhibitors are potentially mediated through their ability to reduce cardiac inflammation, oxidative stress, apoptosis, mitochondrial dysfunction and ionic dyshomeostasis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diabetes mellitus and obesity are growing health concerns. New pharmacologic interventions have recently begun to play a more notable role in the treatment pathway of these separate but related ...conditions. In particular, glucagon-like peptide-1 receptor agonists, such as semaglutides (Ozempic, Wegovy) and tirzepatide (Mounjaro), and sodium glucose co-transporter 2 inhibitors, such as dapagliflozin (Farxiga) and empagliflozin (Jardiance), have emerged as treatment options. Multiple clinical trials have demonstrated their efficacy in regulating metabolism, improving glycemic control, and managing long-term weight reduction. However, glucagon-like peptide-1 receptor agonists have also been associated with gastrointestinal side effects, including delayed gastric emptying as well as regurgitation and aspiration during general anesthesia or deep sedation, and sodium glucose co-transporter 2 inhibitors have been associated with severe diabetic ketoacidosis. Therefore, discontinuation of these medications before surgery is imperative. Given the popularity of these medications among the general public, it is essential for hand surgeons, to understand how to appropriately manage them perioperatively. The objective of this article was to review these new diabetes mellitus and weight loss medications, including their mechanisms of action, indications for use, and perioperative management guidelines. Additionally, we will take this opportunity to review perioperative guidelines for other common medications relevant to patients undergoing procedures involving the hand and upper extremity such as antithrombotic medications and rheumatoid arthritis-related immunosuppressive medications. Finally, we will describe how the electronic medical record system can be used to optimize perioperative medication management in this population.
We present a case of anion gap euglycemic diabetic ketoacidosis (EuDKA) in a patient with COVID-19 infection. Patients with diabetes mellitus are at increased risk of severe illness, and ...hyperglycaemia is associated with higher morbidity and mortality in patients infected with COVID-19.
A 76-year-old male with diabetes mellitus treated with SGLT2 inhibitor tested positive for COVID-19 infection on day 3 after his admission. In the emergency room he had a high anion gap metabolic acidosis and a blood glucose of 248 mg/dl. His urine tested strongly positive for ketones. A diagnosis of euglycemic diabetic ketoacidosis was made and he was treated with intravenous insulin and normal saline; his antidiabetic medications were stopped. His metabolic acidosis gradually resolved, and he was discharged.
Euglycemic diabetic ketoacidosis is a rare complication of COVID-19 infection. It is defined by the American Diabetes Association as the triad of anion gap metabolic acidosis with arterial pH <7.3, serum bicarbonate <18 mmol/l and ketonuria or ketonemia. It is a life-threatening complication which usually occurs in type 1 diabetes mellitus patients but may also occur in type 2 diabetes mellitus patients. As described earlier, it is associated with hyperglycaemia but if blood glucose is low or near normal but <250 mg/dl it is then named euglycemic diabetic ketoacidosis. Patients treated with SGLT2 inhibitors are at increased risk of euglycemic diabetic ketoacidosis.
COVID-19 infection precipitated euglycemic diabetic ketoacidosis in our patient. SGLT2 inhibitors must be stopped when this adverse reaction occurs. As their use increases, the risk of this adverse reaction is higher as well. Their prescription should be restricted to trained physicians who are able to educate their patients and treat them appropriately in situations that may arise.
COVID-19 infected patients are at increased risk of developing diabetic ketoacidosis or euglycemic ketoacidosis when treated with SGLT-2 inhibitors.It is practical to discontinue the drug at the onset of any symptoms consistent with acute infection to prevent the development of euglycemic diabetic ketoacidosis.
Diabetes mellitus and the associated complications represent a global burden on human health and economics. Cardiovascular diseases are the leading cause of death in diabetic patients, who have a 2-5 ...times higher risk of developing heart failure than age-matched non-diabetic patients, independent of other comorbidities. Diabetic cardiomyopathy is defined as the presence of abnormal cardiac structure and performance in the absence of other cardiac risk factors, such coronary artery disease, hypertension, and significant valvular disease. Hyperglycemia, hyperinsulinemia, and insulin resistance mediate the pathological remodeling of the heart, characterized by left ventricle concentric hypertrophy and perivascular and interstitial fibrosis leading to diastolic dysfunction. A change in the metabolic status, impaired calcium homeostasis and energy production, increased inflammation and oxidative stress, as well as an accumulation of advanced glycation end products are among the mechanisms implicated in the pathogenesis of diabetic cardiomyopathy. Despite a growing interest in the pathophysiology of diabetic cardiomyopathy, there are no specific guidelines for diagnosing patients or structuring a treatment strategy in clinical practice. Anti-hyperglycemic drugs are crucial in the management of diabetes by effectively reducing microvascular complications, preventing renal failure, retinopathy, and nerve damage. Interestingly, several drugs currently in use can improve cardiac health beyond their ability to control glycemia. GLP-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors have been shown to have a beneficial effect on the cardiovascular system through a direct effect on myocardium, beyond their ability to lower blood glucose levels. In recent years, great improvements have been made toward the possibility of modulating the expression of specific cardiac genes or non-coding RNAs
for therapeutic purpose, opening up the possibility to regulate the expression of key players in the development/progression of diabetic cardiomyopathy. This review summarizes the pathogenesis of diabetic cardiomyopathy, with particular focus on structural and molecular abnormalities occurring during its progression, as well as both current and potential future therapies.
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