Sodium-glucose Linked Transporter-2 Research Articles

Heart Failure With Type 2 Diabetes Mellitus: Association Between Antihyperglycemic Agents, Glycemic Control, and Ejection Fraction.

Background: Heart failure (HF) is associated with type 2 diabetes mellitus (T2DM). Antihyperglycemic drugs have interaction with heart failure among diabetic patients. To date, the data on real world use of diabetic medication in Malaysian heart failure patients with T2DM has not been elucidated.Objective: This study aims to identify the prescribing pattern of antihyperglycemic regimens in HF patients with T2DM, and to investigate the association between glycemic control and other factors such as demographic and clinical characteristics with left ventricular ejection fraction (LVEF) in these patients.Methods: This retrospective observational study involved patients diagnosed to have HF and T2DM who were seen in the outpatient clinic in a government tertiary hospital in Malaysia. Patients receiving at least one oral antidiabetic agent and/or insulin for at least 3 months prior were included. The differences and association between study outcomes were examined and analyzed using Pearson's Chi-square test, One-Way ANOVA, Binary Logistic Regression and multiple Multinomial Logistic Regression models.Results: From July to December 2019, 194 patients were included in this study. The majority (52.1%) of the patients had HF with preserved ejection fraction (HFpEF), 20.6% had HF with mid-range EF (HFmrEF), and 27.3% had HF with reduced EF (HFrEF). Overall, metformin (59.8%) was the commonest antihyperglycemic agent prescribed, followed by insulins (54.0%), and sulphonylureas (44.9%). The most prescribed agents for HFpEF, HFmrEF, and HFrEF patients were metformin (65.3%), insulins (62.5%), and sulphonylureas (60.4%), respectively. The prescribing trend of sulphonylureas was found to be significantly associated with patients' LVEF status (p = 0.033). The odds for sulphonylurea prescription among the HFrEF patients were 2.42 times higher compared to the HFpEF patients [95% confidence interval [CI], 1.23–4.79]. There was no association found between glycemic control with patients' LVEF.Conclusion: Our findings reported metformin as the most commonly prescribed antihyperglycemic agent, sodium glucose linked transporter-2 (SGLT-2) inhibitor being under-prescribed, and detected poorly controlled diabetes in majority of patients with T2DM and HF. Understanding the prescribing pattern of antihyperglycemic agents supports the implementation of evidence-based treatment in HF patients with T2DM to improve patients' outcomes.

New oral antidiabetic drugs

Aparadigm change in the treatment of type 2 diabetes has recently emerged due to the introduction of new oral antidiabetic agents. Cardiovascular endpoint studies confirmed the safety of dipeptidyl peptidase 4 (DPP-4) inhibitors and a cardiovascular protective effect for glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose linked transporter 2 (SGLT-2) inhibitors. Furthermore, SGLT‑2 inhibitors reduce the risk for heart failure and have a renoprotective effect. These studies led to changes in clinical recommendations and guidelines. In patients with high or very high cardiorenal risk, SGLT‑2 inhibitors or GLP‑1 receptor agonists are recommended for risk protection independent of HbA1c values, with existing or high risk for chronic heart failure SGLT‑2 inhibitors are the preferred choice. Therefore, the choice of antidiabetic treatment strategy is no longer determined by the level of glycosylated hemoglobin (HbA1c) alone but particularly by the cardiorenal risk of the individual patient.

Antihypertensive and Renal Mechanisms of SGLT2 (Sodium-Glucose Linked Transporter 2) Inhibitors.

Empaglifolzin, canagliflozin, and dapagliflozin are SGLT2 (sodium-glucose linked transporter type 2) inhibitors for treatment of type 2 diabetes mellitus that also reduce blood pressure, mortality, and cardiovascular disease and slow the loss of glomerular filtration rate. SGLT2 inhibitors inhibit the coupled reabsorption of sodium and glucose from the proximal tubules, thereby increasing renal glucose and sodium excretion, but they have more widespread renal effects, including inhibition of the sodium:proton exchanger. They increase the delivery of sodium to the loop of Henle and can thereby activate the tubuloglomerular feedback response to correct glomerular hyperfiltration. There are multiple potential mechanisms whereby these drugs lower blood pressure and preserve kidney function that are the focus of this review.

Sodium‐glucose linked transporter‐2 inhibitor renal outcome modification in type 2 diabetes: Evidence from studies in patients with high or low renal risk

Data from three completed cardiovascular outcome trials (CVOTs), EMPA-REG OUTCOME, CANVAS Program and DECLARE-TIMI 58, add to the evidence supporting the potential renoprotective effects of sodium-glucose linked transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes. Despite recommendations in recent guidelines, it is difficult to support a view that definitive evidence for renoprotection exists from these SGLT2 inhibitor CVOT results. To date, the only dedicated trial to report definitive data on the renal impact of SGLT2 inhibition is CREDENCE. Notably, the total number of patient-relevant renal endpoint events (dialysis, transplant or renal death) observed in CREDENCE was significantly higher than the total for all three CVOTs collectively (183 events/4401 patients vs. 69 events/34 322 patients, respectively), which shows the increased statistical power of CREDENCE for these renal endpoints. Treatment with canagliflozin was associated with a 30% relative risk reduction (RRR) in the primary composite endpoint of end-stage kidney disease, doubling of serum creatinine, or death from renal or cardiovascular causes and a 34% RRR for the renal-specific elements of this primary endpoint (P <0.001). Canagliflozin has therefore become the first US-approved SGLT2 inhibitor to include an indication for RRR, in addition to type 2 diabetes glycaemic control and cardiovascular risk reduction. While confirmatory of the exploratory data from CVOTs, CREDENCE provides the first robust data on the effects of canagliflozin on patient-relevant renal endpoints. Extrapolation to a conclusion of a SGLT2 inhibitor class effect cannot be made until additional renal trials with other SGLT2 inhibitors are reported.

Metabolism and disposition of the SGLT2 inhibitor bexagliflozin in rats, monkeys and humans

Bexagliflozin is a C-aryl glucoside inhibitor of human sodium-glucose linked transporter 2 (SGLT2) that undergoes oxidation and glucuronidation to form six principal metabolites in humans.In vitro metabolism by human liver microsomes and recombinant enzymes is primarily mediated by CYP3A4 and UGT1A9. Three major oxidation products and three major glucuronides have been identified in vivo. Metabolism by rats is mostly by oxidation whereas metabolism by monkeys and humans is mostly by glucuronidation. Metabolism by monkeys closely resembles metabolism by humans and all metabolites found in humans are also found in monkeys. A greater diversity of metabolites has been identified among human in vivo specimens than among in vitro reaction products.Following oral dosing of humans with 14C-bexagliflozin, the 3′-O-glucuronide contributed 32% of the parent AUC and all other metabolites contributed <10%. Of the 91.6% of input radioactivity recovered, 51.1% was in faeces, predominantly as bexagliflozin, and 40.5% was in urine, largely as the 3′-O-glucuronide. Unidentified metabolites contributed 0.27% of the input radiolabel.A quantitative accounting for the metabolism and disposition of bexagliflozin in vivo has been developed.

SAT-300 EFFECTS OF DAPAGLIFLOZIN AND DAPAGLIFLOZIN PLUS SAXAGLIPTIN ON HbA1c AND ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE: PHASE II/III DELIGHT STUDY

Suboptimal glycemic control is often associated with albuminuria and decline in estimated GFR (eGFR) in patients with diabetic kidney disease (DKD). Sodium-glucose linked transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have individually been shown to exert benefit on glycemic control and/or albuminuria in patients with DKD. We assessed the effects of the SGLT2 inhibitor dapagliflozin (dapa) alone and in combination with the DPP4 inhibitor saxagliptin (saxa) on albuminuria and HbA1c in patients with Type 2 diabetes and DKD.

Future Strategies in Management of Diabetes Mellitus: A Brief Report

Diabetes Mellitus is a disorder of altered glucose and lipid metabolism having hyperglycemia as characteristic feature. Long term uncontrolled Diabetes Mellitus primarily leads to rise in microvascular and macrovascular events involving many organ systems. Strict glycemic control remains the key to avoid such complications. The management of Diabetes and its co-morbid conditions affect patients not only economically but also psychologically. Currently about nine different varieties of medications are being employed in treatment of Diabetes Mellitus. Even after having many varieties of drugs available co-morbid conditions associated with Diabetes Mellitus are on rise as the global burden of disease is also increasing. In last decade drugs against some new targets in management of Diabetes are approved Glucagon like Peptide-1 (GLP-1) agonist, Dipeptidyl Peptidase-IV (DPP-IV) inhibitors and Sodium-Glucose linked Transporter-2 (SGLT-2) inhibitors and Peroxisome Proliferator-activated receptor –alpha and gamma agonist. Although numerous drugs are available roughly one third patients achieve desired glycemic control that’s why newer drugs acting on novel targets are required. The objective of review is to throw light on newer drug targets which are in various stages of development to have latest drugs against Diabetes.

Research into the Effect of Sodium-Glucose Linked Transporter 2 Inhibition on Left Ventricular Remodeling in Patients with Heart Failure and Diabetes Mellitus

Introduction: DM and heart failure (HF) are lethal, with limited diabetic therapy options. Sodium-glucose linked transporter 2 (SGLT2) inhibitors have been reported to have CV benefits in at risk DM patients. We are the first to study the CV effects of SGLT2 inhibition in patients with DM and HF. Methods: In this randomized double-blind placebo controlled trial, 56 patients (mean age: 67.1 years, males: 66%) with DM and echocardiographically confirmed HF with reduced ejection fraction (HFrEF) on regular diuretic therapy were assigned to dapagliflozin 10mg OD or placebo for one year. Primary endpoint was the difference in left ventricular (LV) volumes between both groups using cardiac MRI. Secondary endpoints include LV mass, LV ejection fraction (EF), weight, BP and diuretic use. Outcomes were analysed using linear regression controlling for baseline values, age, sex and renal function. Results: There was no difference between dapagliflozin and placebo in the primary endpoints of LV end diastolic volume (LVEDV) or LV end systolic volume (LVESV); +4.71mls; 95% CI: -17.to 26.50 and +1.52mls; 95% CI: -15.68 to 18.72 respectively. However, when an interaction term for starting LVEF was added to the model, dapagliflozin significantly lowered LVEDV, LVESV and LV mass in those with starting LVEF ≥ 45%; -15.59mls; p=0.019, -15.20mls; p=0.016 and -4.87gm/m2; p=0.026. Patients on dapagliflozin had weight reduction; -1.90kg; 95% CI: -3.83 to +0.04; p=0.054, lower diastolic BP; -6.34mmHg; 95% CI: -11.35 to -1.32; p=0.014 and higher hemoglobin; +1.23 g/dl; 95% CI: 0.65 to 1.82; p&amp;lt;0.001. They were also more likely to stop or reduce loop diuretics; 50.0% vs. 8.7%; p=0.005. Conclusions: Our data show dapagliflozin treatment resulted in weight and blood pressure reduction among patients with DM and HFrEF. There was evidence to suggest that dapagliflozin may cause LV reverse remodelling in DM patients with mild, but not with more severe HFrEF. Disclosure J.S.S. Singh: None.I. Mordi: None.M. Mohan: None.S.J. Gandy: None. E. Pearson: Speaker's Bureau; Self; Eli Lilly and Company.J.G. Houston: None. A.D. Struthers: Research Support; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca.C.C. Lang: None.

Dapagliflozin improves insulin resistance and glucose intolerance in a novel transgenic rat model of chronic glucose overproduction and glucose toxicity.

To determine whether the excretion of glucose improves insulin resistance, impaired insulin secretion or both. Appropriate methods were used to assess insulin sensitivity (euglycaemic-hyperinsulinaemic clamp) and insulin secretion (hyperglycaemic clamp) in insulin-resistant and hyperglycaemic phosphoenolpyruvate carboxykinase (PEPCK) transgenic rats after treatment with the sodium-glucose co-transporter-2 (SGLT2) inhibitor dapagliflozin. In 14-week-old rats with hyperglycaemia, insulin resistance and glucose intolerance, 6 weeks of dapagliflozin treatment resulted in lower weight gain, plasma glucose and insulin levels, and improved glucose tolerance, associated with enhanced insulin sensitivity (rate of glucose disappearance: 51.6 ± 2.3 vs 110.6 ± 3.9 µmol/min/kg; P < .005) and glucose uptake in muscle (0.9 ± 0.1 vs 1.7 ± 0.3 µmol/min/100 g; P < .05) and fat (0.23 ± 0.04 vs 0.55 ± 0.10 µmol/min/100 g, P < .05). Additionally, adipose tissue GLUT4 protein levels were increased (0.78 ± 0.05 vs 1.20 ± 0.09 arbitrary units; P < .05), adipocyte count was higher (221.4 ± 17.7 vs 302.3 ± 21.7 per mm2 fat area; P < .05) and adipocyte size was reduced (4631.8 ± 351.5 vs 3397.6 ± 229.4 µm2 , P < .05). There was no improvement, however, in insulin secretion. To determine whether earlier intervention is necessary, 5-week-old PEPCK transgenic rats were treated with dapagliflozin for 9 weeks and insulin secretion assessed. Dapagliflozin resulted in improved plasma glucose and insulin levels, and lower weight gain but, again, insulin secretion was not improved. In this transgenic model of low-grade chronic hyperglycaemia, SGLT2 inhibitor treatment resulted in reduced blood glucose and insulin levels and enhanced glucose tolerance, associated with improved muscle and fat insulin resistance but not improved insulin secretory function.

Empagliflozin as a new management strategy on outcomes in patients with type 2 diabetes mellitus

Patients with type 2 diabetes mellitus have an increased risk of cardiovascular (CV) complications. Although hyperglycaemia contributes to the pathogenesis of atherosclerosis and heart failure in these patients, glucose-lowering strategies did not have a significant effect on reducing CV risk, particularly in patients with a long duration of type 2 diabetes mellitus and prevalent CV disease (CVD). Sodium-glucose linked transporter-2 (SGLT2) inhibitors are a new class of anti-hyperglycaemic medications that increase glycaemic control via insulin-dependent mechanism of action associated with increased urinary glucose excretion.In this review, we present an analysis of the Empa-Reg Outcomes investigation, focussed on assessing the CV safety of empagliflozin, an inhibitor of SGLT2. We discuss the impressive results of trials that provide evidence on the cardiac and renal properties of empagliflozin. We present and analyse the current hypothesis on the mechanism of action of glucose-lowering medication, which has such a severe and complex impact on outcomes in patients with type 2 diabetes at high CV risk.

The renal effects of SGLT2 inhibitors and a mini-review of the literature.

Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new and promising class of antidiabetic agents which target renal tubular glucose reabsorption. Their action is based on the blockage of SGLT2 sodium-glucose cotransporters that are located at the luminal membrane of tubular cells of the proximal convoluted tubule, inducing glucosuria. It has been proven that they significantly reduce glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus (T2DM). The glucosuria-induced caloric loss as well as the osmotic diuresis significantly decrease body weight and blood pressure, respectively. Given that SGLT2 inhibitors do not interfere with insulin action and secretion, their efficacy is sustained despite the progressive β-cell failure in T2DM. They are well tolerated, with a low risk of hypoglycemia. Their most frequent adverse events are minor: genital and urinal tract infections. Recently, it was demonstrated that empagliflozin presents a significant cardioprotective effect. Although the SGLT2 inhibitors' efficacy is affected by renal function, new data have been presented that some SGLT2 inhibitors, even in mild and moderate renal impairment, induce significant HbA1c reduction. Moreover, recent data indicate that SGLT2 inhibition has a beneficial renoprotective effect. The role of this review paper is to explore the current evidence on the renal effects of SGLT2 inhibitors.

SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?

While the modest reduction in the primary composite outcome of myocardial infarction, stroke or cardiovascular death in the EMPA-REG Outcomes trial was welcome, the 30–40% reductions in heart failure hospitalisation (HFH) and cardiovascular and all-cause deaths in patients treated with empagliflozin were highly impressive and unexpected. In this review, we discuss briefly why cardiovascular endpoint trials for new diabetes agents are required and describe the results of the first four such trials to have reported, as a precursor to understanding why the EMPA-REG Outcomes results came as a surprise. Thereafter, we discuss potential mechanisms that could explain the EMPA-REG Outcomes results, concentrating on non-atherothrombotic effects. We suggest that the main driver of benefit may derive from the specific effects of sodium-glucose linked transporter-2 (SGLT2) inhibition on renal sodium and glucose handling, leading to both diuresis and improvements in diabetes-related maladaptive renal arteriolar responses. These haemodynamic and renal effects are likely to be beneficial in patients with clinical or subclinical cardiac dysfunction. The net result of these processes, we argue, is an improvement in cardiac systolic and diastolic function and, thereby, a lower risk of HFH and sudden cardiac death. We also discuss whether other drugs in this class are likely to show similar cardiovascular benefits. Finally, areas for future research are suggested to better understand the relevant mechanisms and to identify other groups who may benefit from SGLT2 inhibitor therapy.

Cardiovascular outcome clinical trials in type 2 diabetes mellitus: what are the epidemiological and methodological evidence and the first evaluations to date?

Clinical trials of glucose-lowering strategies in patients with type 2 diabetes mellitus (T2DM) have shown a favorable effect of intensive glycemic control on microvascular complications but failed to show a clear benefit on cardiovascular events. In 2008, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have required stringent criteria to approve new glucose-lowering drugs, demanding proof of cardiovascular safety. As a result of these regulatory requirements, a number of cardiovascular outcome trials in T2DM have been conducted examining the cardiovascular safety of novel glucose-lowering drugs. Dipeptidyl peptidase 4 (DPP4) inhibitors, analogs of glucagon-like peptide 1 (GLP-1), and inhibitors of the renal sodium-glucose linked transporter-2 (SGLT2) are new classes of glucose-lowering drugs for subjects with T2DM. The results of the cardiovascular outcome trials comparing the DPP4 inhibitors saxagliptin, alogliptin, and sitagliptin or the GLP-1 analog lixisenatide to placebo have demonstrated that these drugs are safe. The results of a cardiovascular outcome trial comparing the SGLT2 inhibitor empagliflozin to placebo have been published. Notably, empagliflozin treatment has been associated with a significant reduction in the primary composite cardiovascular outcome. Although the question regarding the positive effect of glycemic control on cardiovascular risk is still unanswered, current evidence suggests that a multifactorial approach aimed at treating not only hyperglycemia but also classical cardiovascular risk factors is necessary in order to reduce the risk of cardiovascular events in patients with T2DM.

A Case Report of Diabetic Ketoacidosis Associated with Multiple Risk Factors Including Dapagliflozin Use

Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new class of antihyperglycemic agents that inhibit renal glucose reabsorption. This group of medications got more popular in diabetic management as it help to control the blood sugar level and it induce weight loss. However, FDA issued a warning of possible association between SGLT2 inhibitors usage and DKA after the reports of several euglycemic DKA cases associated with the use of SGLT2 inhibitors.

Preventing diabetic renal disease: the potential reno-protective effects of SGLT2 inhibitors

Diabetic renal disease is associated with increased cardiovascular risk and is one of the leading causes of end-stage renal disease worldwide. A combination of hyperglycaemia and hypertension drives the development and progression of diabetic renal disease, with glomerular hyperfiltration being an early manifestation of the disease process. Sodium- glucose linked transporter 2 (SGLT2) inhibitors represent a novel class of drugs that lower plasma glucose levels through the inhibition of renal proximal tubular glucose uptake and secondary glycosuria. Clinical evidence that SGLT2 inhibitors attenuate glomerular hyperfiltration is complemented by animal data suggesting that these agents can prevent progression of diabetic renal disease. In clinical studies involving patients with type 1 and type 2 diabetes, SGLT2 inhibition reduces glomerular hyperfiltration and appears (albeit in post-hoc and pooled analyses) to reduce urinary albumin excretion. The longer term potential reno-protective effects of this class of drugs are currently under evaluation in large randomised clinical trials.

New safety warnings for two classes of diabetes drugs: What pharmacists should know

This spring, FDA called attention to two classes of diabetes drugsand potential serious risks associated with them. In April, theEndocrinologic and Metabolic Drugs Advisory Committee advisedFDA to add a heart failure warning to labels on dipeptidyl peptidase–4(DPP-4) inhibitors, also known as gliptins. A month later, FDA issueda drug safety communication warning that another diabetes drug,sodium–glucose linked transporter–2 (SGLT-2) inhibitors, could causeeuglycemic diabetic ketoacidosis.

SGLT-2 inhibition in patients with kidney disease

Accustomed to managing diabetes with agents that mostly act by modulating the secretion and actions of insulin, with the advent of sodium-glucose linked transporter-2 (SGLT-2) inhibitors, physicians are now aware that the kidney also needs to be considered in the spectrum of action of anti-hyperglycaemic agents. Though familiar with the need for dose adjustment when prescribing many of our current anti-hyperglycaemic drugs in the setting of kidney dysfunction, with the SGLT-2 inhibitors pharmacodynamic as well as pharmacokinetic aspects also need to be considered. Finally, through their ability to reduce intraglomerular pressure, systemic blood pressure and plasma uric acid concentration, the SGLT-2 inhibitors offers the possibility of kidney protection. An hypothesis that will need to be tested with long term studies that address changes in the kidney beyond albuminuria, assessing the rate of decline in glomerular filtration rate and ‘hard’kidneyrelated endpoints such as the need for renal replacement therapy (dialysis, transplantation) will be important in this setting.

Sodium–glucose linked transporter-2 inhibitors: potential for renoprotection beyond blood glucose lowering?

The proximal tubule's sodium-glucose linked transporter-2 (SGLT2) accounts for the vast majority of glucose reabsorption by the kidney. Its selective inhibition, accordingly, leads to substantial glycosuria, lowering blood glucose, and facilitating weight loss in individuals with diabetes. During the past year, two SGLT2 inhibitors, canagliflozin and dapagliflozin, have been approved for the treatment of type 2 diabetes. Beyond their anti-hyperglycemic properties, however, this new class of drugs has several other attributes that provide a theoretical basis for kidney protection. Like agents that block the renin-angiotensin system, SGLT2 inhibitors also reduce single-nephron glomerular filtration rate (SNGFR) in the chronically diseased kidney, though by quite different mechanisms. Additional potentially beneficial effects of SGLT2 inhibition include modest reductions in blood pressure and plasma uric acid. Finally, cell culture studies indicate that glucose uptake from the tubular lumen, as well as from the basolateral compartment, can contribute to proximal tubular production of extracellular matrix proteins. Whether such attributes will translate into reducing the progression of chronic kidney disease will require the undertaking of long-term, dedicated studies.

Sodium-glucose-linked transporter 2 inhibitors from Sophora flavescens

During the screening of a prefractionated natural product extract library (400 biota) against sodium-glucose-linked transporter 2 (SGLT2), a methanol fraction of the traditional Chinese medicine, Sophora flavescens, displayed promising inhibitory activity against SGLT2. Based on the medium-pressure column chromatograph and preparative HPLC, bioassay-guided purification on the large-scale organic extract resulted in the isolation of a new isoflavonoid glycoside, 3-(Benzo[d][1,3]dioxol-5-yl)-7-(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-4H-chromen-4-one (1), together with eight known isoflavonoid glycosides 2–9. Except compound 5, other compounds were isolated from this plant for the first time. All nine compounds exhibited inhibitory activity against SGLT2. Among them, compound 9 showed the strongest SGLT2 inhibitory activity with the IC50 value of 2.6 μM, and compound 1 showed the medium SGLT2 inhibitory activity with the IC50 value of 15.3 μM.

Sodium-Glucose linked transporter 2 (SGLT2) inhibitors--fighting diabetes from a new perspective.

Sodium-Glucose linked transporter 2 (SGLT2) inhibitors are a new family of antidiabetic pharmaceutical agents whose action is based on the inhibition of the glucose reabsorption pathway, resulting in glucosuria and a consequent reduction of the blood glucose levels, in patients with type 2 diabetes mellitus. Apart from lowering both fasting and postprandial blood glucose levels, without causing hypoglycemia, SGLT2 inhibitors have also shown a reduction in body weight and the systolic blood pressure. This review paper explores the renal involvement in glucose homeostasis providing also the latest safety and efficacy data for the European Medicines Agency and U.S. Food and Drug Administration approved SGLT2 inhibitors, looking, finally, into the future of this novel antidiabetic category of pharmaceutical agents.