Exposure-Response Analysis of the Sodium-Glucose Cotransporter-2 Inhibitors Dapagliflozin and Empagliflozin on Kidney Hemodynamics in Patients with Type 2 Diabetes.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve markers for renal and cardiovascular outcomes in patients with and without type 2 diabetes (T2D). To assess whether individual differences in plasma drug exposure can explain inter-individual response variation, we characterized the exposure-response relationship for two SGLT2 inhibitors on several clinical and kidney hemodynamic variables. Data were obtained from two studies, RED and RECOLAR, assessing the effects of once-daily 10 mg dapagliflozin or empagliflozin, respectively, on kidney hemodynamics in patients with T2D.

Mechanisms underlying the blood pressure-lowering effects of empagliflozin, losartan and their combination in people with type 2 diabetes: A secondary analysis of a randomized crossover trial.

Aim: To study the effects of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin, the angiotensin receptor blocker (ARB) losartan, and their combination on blood pressure, while studying the mechanisms potentially involved.

Methods: A total of 24 people with type 2 diabetes (T2D) (age: 66 ± 6 years; body mass index: 31.0 ± 3 kg/m ; estimated glomerular filtration rate: 90 ml/min/1.

The Adaptive Renal Response for Volume Homeostasis During 2 Weeks of Dapagliflozin Treatment in People With Type 2 Diabetes and Preserved Renal Function on a Sodium-Controlled Diet.

Introduction: Proximal tubule sodium uptake is diminished following sodium glucose cotransporter 2 (SGLT2) inhibition. We previously showed that during SGLT2 inhibition, the kidneys adapt by increasing sodium uptake at distal tubular segments, thereby maintaining body sodium balance. Despite continuous glycosuria, we detected no increased urine volumes.

Effects of dapagliflozin on volume status and systemic haemodynamics in patients with chronic kidney disease without diabetes: Results from DAPASALT and DIAMOND.

Aims: To assess the effect of sodium-glucose cotransporter-2 inhibitor dapagliflozin on natriuresis, blood pressure (BP) and volume status in patients with chronic kidney disease (CKD) without diabetes.

Materials And Methods: We performed a mechanistic open-label study (DAPASALT) to evaluate the effects of dapagliflozin on 24-hour sodium excretion, 24-hour BP, extracellular volume, and markers of volume status during a standardized sodium diet (150 mmol/d) in six patients with CKD. In parallel, in a placebo-controlled double-blind crossover trial (DIAMOND), we determined the effects of 6 weeks of dapagliflozin on markers of volume status in 53 patients with CKD.

Natriuretic Effect of Two Weeks of Dapagliflozin Treatment in Patients With Type 2 Diabetes and Preserved Kidney Function During Standardized Sodium Intake: Results of the DAPASALT Trial.

Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk for heart failure hospitalization potentially by inducing sodium excretion, osmotic diuresis, and plasma volume contraction. Few studies have investigated this hypothesis, but none have assessed cumulative sodium excretion with SGLT2 inhibition during standardized sodium intake in patients with type 2 diabetes.

Research Design And Methods: The DAPASALT trial was a mechanistic, nonrandomized, open-label study in patients with type 2 diabetes with preserved kidney function on a controlled standardized sodium diet (150 mmol/day).

Renal haemodynamic and protective effects of renoactive drugs in type 2 diabetes: Interaction with SGLT2 inhibitors.

Diabetic kidney disease remains the leading cause of end-stage kidney disease and a major risk factor for cardiovascular disease. Large cardiovascular outcome trials and dedicated kidney trials have shown that sodium-glucose cotransporter (SGLT)2 inhibitors reduce cardiovascular morbidity and mortality and attenuate hard renal outcomes in patients with type 2 diabetes (T2D). Underlying mechanisms explaining these renal benefits may be mediated by decreased glomerular hypertension, possibly by vasodilation of the post-glomerular arteriole.

The effects of dapagliflozin on cardio-renal risk factors in patients with type 2 diabetes with or without renin-angiotensin system inhibitor treatment: a post hoc analysis.

Aims: Renin-angiotensin system inhibitors (RASi) are the most effective treatments for diabetic kidney disease but significant residual renal risk remains, possibly because of other mechanisms of kidney disease progression unrelated to RAS that may be present. Sodium-glucose co-transporter-2 inhibitors reduce albuminuria and may complement RASi by offering additional renal protection. This post hoc analysis investigated the effects of dapagliflozin on cardio-renal risk factors in patients with type 2 diabetes (T2D) with increased albuminuria treated with or without RASi at baseline.

SGLT2 inhibitors' interaction with other renoactive drugs in type 2 diabetes patients: still a lot to learn.

The first cardiovascular (CV) safety trial conducted with a sodium-glucose cotransporter (SGLT)-2 inhibitor, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), reported not only remarkable risk reductions in CV outcome, but also impressive improvements in renal outcome. Changes in renal hemodynamics could be involved in the benefit of SGLT2 inhibitors on renal outcomes. Considering that all patients of EMPA-REG OUTCOME had established atherosclerotic CV disease at baseline, many patients were also treated with several CV drugs at baseline, including RAS blockers, diuretics, calcium-channel blockers, and nonsteroidal anti-inflammatory drugs.

Sodium glucose cotransporter (SGLT)-2 inhibitors: Do we need them for glucose-lowering, for cardiorenal protection or both?

Sodium glucose cotransporter (SGLT)-2 inhibitors are the newest addition to our treatment armamentarium for the management of hyperglycemia in type 2 diabetes. Glucose-lowering per se reduces the risk of microvascular complications, but not the risk of cardiovascular disease, including heart failure and cardiovascular mortality. Also, even when embedded in optimal cardiovascular prevention, a large residual risk remains with respect to progression of diabetic kidney disease.

Mineralocorticoid Antagonism and Diabetic Kidney Disease.

Purpose Of Review: Type 2 diabetes (T2D) is associated with an increased risk of diabetic kidney disease (DKD), cardiovascular disease, and heart failure, in part through activation of the renin-angiotensin-aldosterone system (RAAS). Although recent cardiovascular outcome trials have identified newer therapeutic agents such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1)-receptor agonists that reduce the risk of these complications, patients still exhibit residual cardiorenal morbidity and mortality. Accordingly, the identification of pharmacological agents that attenuate micro- and macrovascular complications related to T2D is a major priority.