SGLT2 inhibitors

AIMS: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI...

BACKGROUND: Limited direct comparative studies exist in terms of the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase-4 inhibitors (DPP4is) on the kidney outcomes in Japanese individuals with type 2 diabetes. METHODS: This retrospective cohort study included 561 Japanese adults with type 2 diabetes, who were newly prescribed either an SGLT2i or a DPP4i and had an eGFR ≥ 30 mL/min/1.73 m2 . The cohort comprised 207 women and 354 men, with a mean (± standard deviation) age of 63 (± 12) years...

Diabetic kidney disease (DKD) is a chronic microvascular complication in patients with diabetes mellitus (DM) and the leading cause of end-stage kidney disease (ESKD). Although glomerulosclerosis, tubular injury and interstitial fibrosis are typical damages of DKD, the interplay of different processes (metabolic factors, oxidative stress, inflammatory pathway, fibrotic signaling, and hemodynamic mechanisms) appears to drive the onset and progression of DKD. A growing understanding of the pathogenetic mechanisms, and the development of new therapeutics, is opening the way for a new era of nephroprotection based on precision-medicine approaches...

Pancreatic carcinoma is a highly aggressive tumor that usually presents when it has already metastasized. Therapeutic options for cure remain scarce and rely on combination chemotherapy with limited sustainability. Diabetes is considered an important risk factor for the development of pancreatic cancer due to the production of proinflammatory cytokines, which result in increased cell proliferation. More than half of patients diagnosed with pancreatic cancer eventually develop diabetes due to the destruction of insulin-producing cells...

(1) Background : This single-center retrospective study aimed to evaluate whether sodium-glucose cotransporter-2 inhibitors (SGLT2-i) therapy may have a nephroprotective effect to prevent contrast-induced acute kidney injury (CI-AKI) in patients with heart failure (HF) undergoing iodinated contrast medium (ICM) invasive procedures. (2) Methods : The population was stratified into SGLT2-i users and SGLT2-i non-users according to the chronic treatment with gliflozins. The primary endpoint was CI-AKI incidence during hospitalization...

Chronic kidney disease (CKD) is a slowly progressive condition characterized by decreased kidney function, tubular injury, oxidative stress, and inflammation. CKD is a leading global health burden that is asymptomatic in early stages but can ultimately cause kidney failure. Its etiology is complex and involves dysregulated signaling pathways that lead to fibrosis. Transforming growth factor (TGF)-β is a central mediator in promoting transdifferentiation of polarized renal tubular epithelial cells into mesenchymal cells, resulting in irreversible kidney injury...

Heart failure (HF) management in type 1 diabetes (T1D) is particularly challenging due to its increased prevalence and the associated risks of hospitalization and mortality, driven by diabetic cardiomyopathy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-is) offer a promising avenue for treating HF, specifically the preserved ejection fraction variant most common in T1D, but their utility is hampered by the risk of euglycemic diabetic ketoacidosis (DKA). This review investigates the potential of SGLT2-is in T1D HF management alongside emergent Continuous Ketone Monitoring (CKM) technology as a means to mitigate DKA risk through a comprehensive analysis of clinical trials, observational studies, and reviews...

The early pathogenetic mechanism of diabetic retinopathy (DR) and its treatment remain unclear. Therefore, we investigated the early pathogenic alterations in DR using streptozotocin-induced diabetic mice and the protective effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors against these alterations. Retinal vascular leakage was assessed by dextran fluorescence angiography. Retinal thickness and vascular leakage were increased 2 and 4 weeks after onset of diabetes, respectively. Immunostaining showed that morphological change of microglia (amoeboid form) was observed at 2 weeks...

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established...

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular and renal benefits in patients with type 2 diabetes mellitus, heart failure, or chronic kidney disease. Since the first studies with these drugs, an initial increase in hemoglobin/hematocrit levels was observed, which was attributed to an increase in hemoconcentration associated with its diuretic effect, although it was early appearent that these drugs increased erythropoietin levels and erythropoiesis, and improved iron metabolism...

Heart failure (HF) with preserved ejection fraction (HFpEF) refers to a clinical condition in which the signs of HF, such as pulmonary congestion, peripheral edema and increased natriuretic-peptide levels, are present despite normal ejection-fractions and the absence of other causes (e.g. pericardial disease). The ejection-fraction cutoff for the definition of HFpEF has varied in the past, but recent society guidelines have settled on a consensus of 50%. HFpEF is particularly common in the elderly. The aim of this narrative review is to summarize the available literature regarding HFpEF in the elderly in terms of evidence for the age-dependence, specific clinical features and underlying mechanisms...

AIMS: To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers. METHODS: Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity. RESULTS: Thirty-eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8...

Patients with type 2 diabetes (T2D) are frequently exposed to comorbidities, mainly cardiovascular complications. Thus, a polypharmacy is often mandatory, targeting not only T2D but also comorbidities such as coronary artery disease and heart failure. Interestingly, some drugs improve glucose control, cardiovascular prognosis and heart failure outcome. This versatility may cause trouble regarding prescriptions by practitioners, especially because of the restricted conditions for the reimbursement in Belgium...

No abstract text is available yet for this article.

Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) have gained prominence in the treatment of diabetes mellitus type 2, heart failure, and chronic kidney disease. However, concerns arise for frail older adults, given their underrepresentation in trials and heightened susceptibility to adverse drug events. This review summarizes the clinical effects of SGLT2 inhibitors in older adults with frailty. SGLT2 inhibitors seem to exhibit consistent cardiovascular benefits irrespective of age. As such, these drugs can be beneficial for older adults with 'cardiovascular frailty': in other words, cardiovascular multimorbidity...

Accumulating evidence has demonstrated that both SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1Ra) have protective effects in patients with diabetic kidney disease. Combination therapy with SGLT2i and GLP1Ra is commonly used in patients with type 2 diabetes (T2D). We previously reported that in combination therapy of SGLT2i and GLP1Ra, the effect on the renal composite outcome did not differ according to the preceding drug. However, it remains unclear how the initiation of combination therapy is associated with the renal function depending on the preceding drug...

Although several randomized clinical trials have reported the potential benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in reducing blood pressure (BP), whether SGLT2i can reduce incident hypertension is unknown. We analyzed individuals with diabetes who were newly prescribed SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) in a large-scale epidemiological database. The primary outcome was the incidence of hypertension. A propensity score matching algorithm was employed to compare the subsequent development of hypertension between the SGLT2i and DPP4i groups...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. OBJECTIVES: The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. METHODS: DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks...