Sglt2 receptors

Chronic diseases, such as type 2 diabetes (T2D), are difficult to manage because they demand continuous therapeutic review and monitoring. Beyond achieving the target HbA1c, new guidelines for the therapy of T2D have been introduced with the new groups of antidiabetics, glucagon-like peptide-1 receptor agonists (GLP-1ra) and sodium-glucose cotransporter-2 inhibitors (SGLT2-in). Despite new guidelines, clinical inertia, which can be caused by physicians, patients or the healthcare system, results in T2D not being effectively managed...

Diabetic kidney disease (DKD) is a substantial complication of type 2 diabetes (T2D), presenting challenges in chronic kidney disease (CKD) management. In addition to traditional and recent therapies, including angiotensin, converting enzyme (ACE) inhibitors, angiotensin receptor blockers, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists, the evolution of antihyperglycemic treatments has introduced a promising agent, glucagon-like peptide-1 receptor agonist (GLP-1RA) for the management of DKD...

The prevention and treatment strategies for heart failure (HF) have evolved in the past two decades. The stages of HF have been redefined, with recognition of the pre-HF state, which encompasses asymptomatic patients who have developed either structural or functional cardiac abnormalities or have elevated plasma levels of natriuretic peptides or cardiac troponin. The first-line treatment of patients with HF with reduced ejection fraction includes foundational therapies with angiotensin receptor-neprilysin inhibitors, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β-blockers, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors and diuretics...

AIM: To compare the risk of developing kidney outcomes with use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus use of sodium-glucose cotransporter-2 (SGLT2) inhibitors among individuals with diabetes. MATERIALS AND METHODS: In this retrospective observational study, we analysed 12 338 individuals with diabetes who newly initiated SGLT2 inhibitors or GLP-1RAs using data from the JMDC claims database. The primary outcome was change in the estimated glomerular filtration rate (eGFR), estimated using a linear mixed-effects model...

Nonalcoholic fatty liver disease (NAFLD) prevalence is rising globally with no pharmacotherapies approved. Hepatic steatosis is closely associated with progression and prognosis of NAFLD. Dapagliflozin, kind of sodium-glucose cotransporter 2 (SGLT2) inhibitor, was found to improve NAFLD in clinical trials, while the underlying mechanism remains poorly elucidated. Here, we reported that dapagliflozin effectively mitigated liver injury and relieved lipid metabolism disorders in vivo. Further investigation showed that dapagliflozin markedly suppressed Liver X Receptor α (LXRα)-mediated synthesis of de novo lipids and bile acids (BAs)...

PURPOSE OF REVIEW: Lupus nephritis is a common complication of systemic lupus erythematosus and is associated with significant morbidity and mortality. The utility of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of lupus nephritis is currently uncertain. Here, we summarize the rationale for their use among patient with lupus nephritis. RECENT FINDINGS: SGLT2 inhibitors were initially developed as antihyperglycemic agents. They have since been shown to have additional, profound effects to slow the progression of chronic kidney disease and lessen the long-term risks of cardiovascular disease in large clinic trials of patients with chronic kidney disease, with and without diabetes, as well as in patients with and without proteinuria...

Aggressive therapy of diabetic kidney disease (DKD) can not only slow the progression of DKD to renal failure but, if utilized at an early enough stage of DKD, can also stabilize and/or reverse the decline in renal function. The currently recognized standard of therapy for DKD is blockade of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). However, unless utilized at a very early stage, monotherapy with these drugs in DKD will only prevent or slow the progression of DKD and will neither stabilize nor reverse the progression of DKD to renal decompensation...

BACKGROUND AND OBJECTIVES: Recent studies have shown that the imbalance of intestinal flora is related to the occurrence and progression of diabetic nephropathy (DN) and can affect lipid metabolism. Sodium-dependent glucose transporters 2 (SGLT2) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist are commonly used hypoglycemic drugs and have excellent renal safety. The purpose of this study was to compare the protective effects of empagliflozin and liraglutide on kidneys, lipid metabolism, and intestinal microbiota in diabetic mice...

Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage kidney disease (ESKD). Vasopressin plays a pivotal role in ADPKD progression; therefore, the selective vasopressin V2 receptor antagonist tolvaptan is used as a key drug in the management of ADPKD. On the other hand, sodium-glucose cotransporter-2 inhibitors (SGLT2i), which may possibly stimulate vasopressin secretion due to the diuretic effect of the drug, have been shown to have both renal and cardioprotective effects in various populations, including those with non-diabetic chronic kidney disease...

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have attracted significant attention for their broader therapeutic impact beyond simply controlling blood sugar levels, particularly in their ability to influence inflammatory pathways. This review delves into the anti-inflammatory properties of SGLT2 inhibitors, with a specific focus on canagliflozin, empagliflozin, and dapagliflozin. One of the key mechanisms through which SGLT2 inhibitors exert their anti-inflammatory effects is by activating AMP-activated protein kinase (AMPK), a crucial regulator of both cellular energy balance and inflammation...

OBJECTIVES: Empagliflozin, a sodium-dependent glucose co-transporter 2 (SGLT2) inhibitor, and liraglutide, a GLP-1 receptor (GLP-1R) agonist, are commonly recognized for their cardiovascular benefits in individuals with type 2 diabetes (T2D). In prior studies, we have demonstrated that both drugs, alone or in combination, were able to protect cardiomyocytes from injury induced by diabetes. Mechanistic investigations also suggested that the cardioprotective effect may be independent of diabetes In this study, we utilized a hypoxia-reoxygenation (H/R) model to investigate the cardiovascular benefits of SGLT2 inhibitor empagliflozin and GLP-1 receptor (GLP-1R) agonist liraglutide, both alone and in combination, in the absence of T2D...

Sodium-glucose co-transporter 2 (SGLT2) inhibitor, an efficacious anti-diabetic agent, which has cardiovascular and renal benefits, can promote pancreatic β-cell regeneration in type 2 diabetic mice. However, the underlying mechanism remains unclear. In this study, we aimed to use multi-omics to identify the mediators involved in β-cell regeneration induced by dapagliflozin. We showed that dapagliflozin lowered blood glucose level, upregulated plasma insulin level, and increased islet area in db/db mice...

CONTEXT: The coexistence of diabetes mellitus and atrial fibrillation (AF) is associated with substantial risks of adverse cardiovascular events. OBJECTIVE: The relevant outcomes associated with the use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus glucagon-like peptide-1 receptor agonists (GLP-1RA) among patients with type 2 diabetes (T2D) with/without concomitant AF remained unknown. METHODS: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, there were 344,392 and 31,351 patients with T2D without AF, and 11,462 and 816 T2D patients with AF treated with SGLT2i and GLP-1RA from May 1, 2016, to December 31, 2019...

PURPOSE: In patients with bilateral primary hyperaldosteronism (PA) and those with unilateral PA who are unwilling or unable to undergo adrenalectomy an increase in plasma renin activity (PRA) provided by mineralocorticoid receptor antagonists (MRAs) therapy reflects sufficient antagonism for elevated aldosterone. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) have cardiovascular, renal protective properties and some clinical data have shown an increase in PRA levels with SGLT2-i...

INTRODUCTION: The evolution of treatment for diabetic nephropathy illustrates how basic biochemistry and physiology have led to new agents such as SGLT2 inhibitors and mineralocorticoid blockers. Conversely, clinical studies performed with these agents have suggested new concepts for investigational drug development. We reviewed currently available treatments for diabetic nephropathy and then analyzed early clinical trials of new agents to assess the potential for future treatment modalities...

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease affecting almost 30% of the world population. Approximately 25% of people with NAFLD develop nonalcoholic steatohepatitis (NASH), the fulminant version of the disease. Diabetes mellitus is present in 22.5% of people with NAFLD and 44.60% of individuals with NASH. This review was undertaken to examine the current contribution of glucagon-like peptide 1 (GLP-1) receptor agonists to the pharmacotherapy of diabetic nonalcoholic steatohepatitis...

BACKGROUND: Despite new pharmacotherapy, most patients with long-term Type 2 Diabetes are still hyperglycemic. This could have been solved by insulin with its unlimited potential efficacy, but its dynamic physiology demands frequent titrations which are overdemanding. This report provides a real-life account for a scalable transformation of diabetes care in a community-based endocrinology center by harnessing AI-based autonomous insulin titration. METHODS: The center embedded the d-Nav® technology and its dedicated clinical support...

AIMS: Sodium glucose co-transporter 2 inhibitors (SGLT2is) and/or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with proven cardio- and reno-protective benefits are recommended in people with type 2 diabetes (T2D) at high risk of cardiovascular disease, chronic kidney disease, and/or heart failure. This pooled analysis compared efficacy and safety outcomes of iGlarLixi with or without SGLT2is in people with T2D. METHODS: This post hoc analysis evaluated outcomes in participants who were receiving an SGLT2i when initiating iGlarLixi (SGLT2i users) and those who were not (SGLT2i non-users) in a pooled dataset from three trials: LixiLan-G (advancing from a GLP-1 RA), SoliMix and LixiLan ONE CAN (advancing from basal insulin)...

PURPOSE: This study was to investigate the association between the use of Sodium-glucose Cotransporter-2 inhibitors (SGLT2i) or angiotensin receptor-neprilysin inhibitor (ARNI; ie, Sacubitril + valsartan, Product name ENTRESTO) and the risk of atherosclerotic cardiovascular disease (ASCVD) in patients with coexisting diabetes and heart failure. Specifically, the study compared outcomes between patients using SGLT2i or valsartan + sacubitril and those not using these medications...

IMPORTANCE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with lower anemia risk, based on findings from post hoc analyses of the CREDENCE and DAPA-CKD trials; however, the effectiveness of SGLT2 inhibitors in a more generalizable type 2 diabetes (T2D) and chronic kidney disease (CKD) population, with active comparisons pertinent to current practice, is unknown. OBJECTIVE: To evaluate and compare anemia incidence between SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among patients with T2D and CKD stages 1 to 3...