SLGT2

Results from cardiovascular outcomes trials (CVOTs) in people with Type 2 diabetes (T2D), such as the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) study with dulaglutide, have led to a shift toward glucose lowering therapies that provide broad benefits, including cardiovascular (CV) risk reduction and renoprotection. Dulaglutide reduces atherosclerotic CV outcomes (hazard ratio 0.88; 95% CI: 0.79-0.99) and composite kidney outcomes (hazard ratio 0.85; 95% CI: 0.77-0.93) in people with T2D with high risk or established CV disease...

Diabetes mellitus is associated with endothelial dysfunction that leads to cardiovascular complications. Sodium-glucose cotransporter 2 (SGLT2) inhibitors demonstrated efficacy in glycemic control in type 2 diabetes patients with positive cardiovascular outcome. Recent research revealed a link between SGLT2 inhibition and improved macro- and microvascular endothelial functions. Mechanisms underlying this phenomenon could be due to the role of SLGT2 in the regulation of endothelial physiology. In this review, current knowledge and hypothesis on the link between SGLT2 and endothelial function were critically appraised and the impact of SGLT2 inhibitors on endothelial dysfunction in pre-clinical and clinical studies was discussed...

Diabetic cardiomyopathy is more prevalent in people with type 2 diabetes mellitus (T2DM) than previously recognized, while often being characterized by diastolic dysfunction in the absence of systolic dysfunction. This likely contributes to why heart failure with preserved ejection fraction is enriched in people with T2DM vs. heart failure with reduced ejection fraction. Due to revised mandates from major health regulatory agencies, all therapies being developed for the treatment of T2DM must now undergo rigorous assessment of their cardiovascular risk profiles prior to approval...

Type 2 diabetes mellitus (DM) patients are at high risk for the development of severe COVID-19. Euglycemic diabetic ketoacidosis (eu-DKA) is a rare life-threatening complication associated with the use of SGLT2 inhibitor that may be unnoticed, particularly in a pandemic setting, due to the absence of significant hyperglycemia, delaying its treatment. In this report, we describe a case of a 56-year-old patient who presented an elevated anion gap metabolic acidosis during a SARS-CoV-2 infection and was diagnosed with SGLT2-associated euglycemic diabetic ketoacidosis...

OBJECTIVE: Phthalates are non-persistent pollutants related to impaired metabolism and high cardiovascular risk. Their toxic metabolites are eliminated through urine and feces. Prevention policies are considered by the governments, although no therapeutic strategy to facilitate their elimination from the human body has been proposed so far. Aim of the present study was to verify, for the first time in humans, whether diuretics might be able to enhance phthalates' toxic metabolites urinary output...

The alarming increase in the number of diabetic patients worldwide raises concerns regarding the impact of the disease on global health, not to mention on social and economic aspects. Furthermore, the association of this complex metabolic disorder with male reproductive impairment is worrying, mainly due to the increasing chances that young individuals, at the apex of their reproductive window, could be affected by the disease, further contributing to the disturbing decline in male fertility worldwide. The cornerstone of diabetes management is glycemic control, proven to be effective in avoiding, minimizing or preventing the appearance or development of disease-related complications...

PURPOSE OF REVIEW: Diabetes and heart failure commonly coexist and portend worsened prognosis than either disease alone. We explore mechanisms that may serve as potential treatment targets and review the effects of various contemporary glucose-lowering agents on heart failure outcomes. RECENT FINDINGS: Promising data has emerged on sodium-glucose cotransporter 2 (SLGT2) inhibitors as the first class of agents to improve cardiovascular mortality and heart failure outcomes in diabetic individuals both with and without established heart failure...

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BACKGROUND: Sodium-glucose cotransporter 2 (SLGT2) inhibitors has been associated with an increased risk of genital infections secondary to increased glycosuria. CASE REPORT: We report a case of a 41-year-old man with type 2 diabetes treated with empagliflozin and metformin who presented with scrotal swelling. He described multiple preceding episodes of genital thrush for which he self-administered over-the-counter anti-fungal treatment. On examination, he was afebrile and hemodynamically stable...

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive chronic disease associated with severe microvascular and macrovascular complications. Our aim is to assess the real world effectiveness of SGT" inhibitors in achieving metabolic therapeutic goals. METHODS: A retrospective, observational study. Inclusion criteria for patients were a previous diagnosis of type 2 diabetes mellitus, age > 18 years, patients receiving either dapagliflozin 10 mg and/or canagliflozin 300 mg...

BACKGROUND: Heart failure (HF) and diabetes (DM) are a lethal combination. The current armamentarium of anti-diabetic agents has been shown to be less efficacious and sometimes even harmful in diabetic patients with concomitant cardiovascular disease, especially HF. Sodium glucose linked co-transporter type 2 (SGLT2) inhibitors are a new class of anti-diabetic agent that has shown potentially beneficial cardiovascular effects such as pre-load and after load reduction through osmotic diuresis, blood pressure reduction, reduced arterial stiffness and weight loss...

UNLABELLED: Drugs that inhibit the sodium-glucose co-transporter-2 (SGLT2) are an exciting novel, insulin-independent treatment for diabetes that block glucose reabsorption from the proximal tubules of the kidney, leading to increased glucose excretion and lower blood glucose levels. Inhibition of SGLT2 activity also reduces sodium reabsorption, which together with glycosuria produces a mild diuretic effect with the potential for dehydration and hyperkalemia. We report on a 60-year-old man with uncontrolled type 2 diabetes treated with insulin, glimepiride, metformin and canagliflozin, who was admitted with altered mental status after a syncopal episode...

OBJECTIVE: Following the first Food and Drug Administration (FDA) approval in 2013, sodium glucose cotransporter 2 (SGLT2) inhibitors have generated much interest among physicians treating patients with type 2 diabetes mellitus (T2DM). Here, the role in treatment with this drug class is considered in the context of T2DM treatment paradigms. METHODS: The clinical trials for the SGLT2 inhibitors are examined with a focus on canagliflozin, dapagliflozin, and empagliflozin...

The maintenance of normal glucose homeostasis requires a complex, highly integrated interaction among the liver, muscle, adipocytes, pancreas and neuroendocrine system. Recent studies have showed that the kidneys also play a central role in glucose homeostasis by reabsorbing all the filtered glucose, an adaptive mechanism that ensures sufficient energy is available during fasting periods. This mechanism becomes maladaptive in diabetes, however, as hyperglycaemia augments the expression and activity of the sodium-glucose cotransporter (SGLT) 2 in the proximal tubule of the kidney...

CONTEXT: Sodium-glucose cotransporter 2 (SGLT2) expressed in the proximal renal tubules accounts for about 90% of the reabsorption of glucose from tubular fluid. Genetic defects of SGLT2 result in a benign familial renal glucosuria. Pharmacological agents that block SGLT2 are being tested as potential treatment for type 2 diabetes mellitus. EVIDENCE ACQUISITION: A Pubmed search was used to identify all relevant articles on the physiology of SGLTs as well as published preclinical and clinical experimental studies with SGLT2 inhibitors; a reference search of all retrieved articles was also undertaken...