Kidney hemodynamic profile and systemic vascular function in adults with type 2 diabetes: Analysis of three clinical trials.

Aims: Glomerular hyperfiltration plays a key role in the pathophysiology of diabetic kidney disease (DKD). Mechanisms underlying this adverse hemodynamic profile are incompletely understood. We hypothesized that systemic vascular pathology, including endothelial dysfunction and arterial stiffness, relates to glomerular hyperfiltration indicated by filtration fraction (FF).

Postprandial renal haemodynamic effects of the dipeptidyl peptidase-4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS): A predefined substudy of a randomized, double-blind trial.

Aim: To determine the effect of the dipeptidyl peptidase-4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D).

Materials And Methods: In this predefined substudy within a randomized, double-blind, parallel-group, intervention trial, overweight people with T2D without renal impairment were treated with once-daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as an add-on to metformin for 8 weeks. After a standardized liquid protein-rich meal, the glomerular filtration rate (GFR) and effective renal plasma flow were determined by inulin and para-aminohippuric acid clearance, respectively, based on timed urine sampling.

The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes.

Glucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured as urinary nucleic acid oxidation in persons with type 2 diabetes. Post-hoc analysis of two independent, randomised, placebo-controlled and double-blinded clinical trials.

Kidney hemodynamic function in men and postmenopausal women with type 2 diabetes and preserved kidney function.

The progression of kidney disease may differ between sexes in type 2 diabetes (T2D), with previous studies reporting a slower decline in women. Glomerular hyperfiltration is a key factor driving the kidney function decline. The current study aimed to investigate the differences in kidney hemodynamic function between men and women with T2D.

Effects of DPP-4 Inhibitor Linagliptin Versus Sulfonylurea Glimepiride as Add-on to Metformin on Renal Physiology in Overweight Patients With Type 2 Diabetes (RENALIS): A Randomized, Double-Blind Trial.

Objective: To compare effects of the dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin with those of a sulfonylurea on renal physiology in metformin-treated patients with type 2 diabetes mellitus (T2DM).

Research Design And Methods: In this double-blind randomized trial, 46 overweight T2DM patients without renal impairment received once-daily linagliptin (5 mg) or glimepiride (1 mg) for 8 weeks. Fasting glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid clearances.

Effects of dipeptidyl peptidase-4 inhibitor linagliptin versus sulphonylurea glimepiride on systemic haemodynamics in overweight patients with type 2 diabetes: A secondary analysis of an 8-week, randomized, controlled, double-blind trial.

Aim: To determine the glucose-independent effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin versus the sulphonylurea glimepiride on systemic haemodynamics in the fasting and postprandial state in patients with type 2 diabetes (T2D).

Materials And Methods: In this prespecified secondary analysis of a phase IV, double-blind trial, 46 metformin-treated, overweight patients with T2D were included and randomly assigned (1:1) to once-daily linagliptin (5 mg) or glimepiride (1 mg) for 8 weeks. In a sub-study involving 26 patients, systemic haemodynamics were also assessed following a standardized liquid meal (Nutridrink Yoghurt style).

The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve hard renal outcomes in type 2 diabetes. This is possibly explained by the fact that SGLT2i normalize the measured glomerular filtration rate (mGFR) by increasing renal vascular resistance, as was shown in young people with type 1 diabetes and glomerular hyperfiltration. Therefore, we compared the renal hemodynamic effects of dapagliflozin with gliclazide in type 2 diabetes.

Renal sinus fat and renal hemodynamics: a cross-sectional analysis.

Objectives: Increased renal sinus fat (RSF) is associated with hypertension and chronic kidney disease, but underlying mechanisms are incompletely understood. We evaluated relations between RSF and gold-standard measures of renal hemodynamics in type 2 diabetes (T2D) patients.

Methods: Fifty-one T2D patients [age 63 ± 7 years; BMI 31 (28-34) kg/m; GFR 83 ± 16 mL/min/1.

Plasma uric acid and renal haemodynamics in type 2 diabetes patients.

Aim: Increased plasma uric acid (PUA) concentrations are associated with chronic kidney disease in type 2 diabetes (T2D) patients. The mechanisms involved remain unclear. We investigated the relation between PUA and (intra)renal haemodynamics in T2D patients without overt kidney disease.

GLP-1 receptor agonists do not affect sodium intake: Exploratory analyses from two randomized clinical trials.

Objectives: Excessive sodium intake, despite current dietary advice, remains a global issue with cardiovascular and renal consequences. The aim of this study was to determine whether glucagon-like peptide receptor agonists (GLP-1 RAs), used as antihyperglycemic agents for type 2 diabetes (T2DM) management, may reduce salt cravings as they are known to reduce hedonic feeding behavior and are involved in sodium homeostasis by increasing renal sodium excretion.

Methods: We performed exploratory analyses using data from two randomized, clinical crossover trials, which primarily aimed to assess the effects of GLP-1 RAs on central satiety and reward circuits and subsequent related feeding behavior.

Assessment of real-time and quantitative changes in renal hemodynamics in healthy overweight males: Contrast-enhanced ultrasonography vs para-aminohippuric acid clearance.

Objective: To determine the ability of renal contrast-enhanced ultrasonography (CEUS) to detect acute drug-induced changes in renal perfusion (using the glucagon-like peptide (GLP)-1 receptor agonist exenatide and nitric oxide [NO]-synthase inhibitor L-N -monomethyl arginine [l-NMMA]), and assess its correlation with gold standard-measured effective renal plasma flow in humans.

Methods: In this prespecified exploratory analysis of a placebo-controlled cross-over study, renal hemodynamics was assessed in 10 healthy overweight males (aged 20-27 years; BMI 26-31 kg/m ) over two separate testing days; during placebo (isotonic saline) and subsequent exenatide infusion (Day-A), and during l-NMMA, and subsequent exenatide plus l-NMMA infusion (Day-B). Renal cortical microvascular blood flow was estimated following microbubble infusion and CEUS destruction-refilling-sequences.

Exenatide twice-daily does not affect renal function or albuminuria compared to titrated insulin glargine in patients with type 2 diabetes mellitus: A post-hoc analysis of a 52-week randomised trial.

Aims: To compare the effects of long-term treatment with the GLP-1RA exenatide twice-daily versus titrated insulin glargine (iGlar) on renal function and albuminuria in type 2 diabetes (T2DM) patients.

Methods: We post-hoc evaluated renal outcome-data of 54 overweight T2DM patients (mean  ± SD age 60 ± 8 years, HbA1c 7.5 ± 0.

Renal tubular effects of prolonged therapy with the GLP-1 receptor agonist lixisenatide in patients with type 2 diabetes mellitus.

Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are well-established glucose-lowering drugs for type 2 diabetes mellitus (T2DM) management. Acute GLP-1RA administration increases urinary excretion of sodium and other electrolytes. However, the renal tubular effects of prolonged GLP-1RA treatment are largely unknown.

Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial.

Background: The results of the ELIXA trial demonstrated the cardiovascular safety of lixisenatide, a short-acting glucagon-like peptide-1 receptor agonist, in patients with type 2 diabetes and acute coronary syndrome. In this exploratory analysis of ELIXA, we investigate the effect of lixisenatide on renal outcomes.

Methods: ELIXA was a randomised, double-blind, placebo-controlled trial, done at 828 sites in 49 countries.

Lixisenatide Versus Insulin Glulisine on Fasting and Postbreakfast Systemic Hemodynamics in Type 2 Diabetes Mellitus Patients.

The prolonged treatment effects of a short-acting GLP-1RA (glucagon-like peptide-1 receptor agonist), such as lixisenatide, on fasting and postprandial systemic hemodynamics in type 2 diabetes mellitus patients are unknown. In this secondary analysis, we included 34 overweight insulin glargine-treated type 2 diabetes mellitus patients (mean±SD age, 62±7 years; HbA, 8.0±0.

Effect of immediate and prolonged GLP-1 receptor agonist administration on uric acid and kidney clearance: Post-hoc analyses of four clinical trials.

Aims: To determine the effects of glucagon-like peptide (GLP)-1 receptor agonists (RA) on uric acid (UA) levels and kidney UA clearance.

Material And Methods: This study involved post-hoc analyses of 4 controlled clinical trials, which assessed actions of GLP-1RA administration on kidney physiology. The immediate effects of GLP-1RA exenatide infusion vs placebo were determined in 9 healthy overweight men (Study-A) and in 52 overweight T2DM patients (Study-B).

GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes.

The gastrointestinal tract - the largest endocrine network in human physiology - orchestrates signals from the external environment to maintain neural and hormonal control of homeostasis. Advances in understanding entero-endocrine cell biology in health and disease have important translational relevance. The gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) is secreted upon meal ingestion and controls glucose metabolism by modulating pancreatic islet cell function, food intake and gastrointestinal motility, amongst other effects.

Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week, randomised, open-label trial.

Aim: To determine whether lixisenatide, a prandial short-acting glucagon-like peptide receptor agonist (GLP-1RA), ameliorates postprandial glomerular hyperfiltration in patients with type 2 diabetes mellitus (T2DM) compared with insulin-glulisine (iGlu).

Methods: Postprandial renal haemodynamic effects of 8-week treatment with lixisenatide 20 µg vs once-daily titrated iGlu were measured in 35 overweight patients with T2DM inadequately controlled on insulin-glargine, with or without metformin [mean ± SD age 62 ± 7 years, HbA1c 8.0% ± 0.

SGLT2 Inhibition in the Diabetic Kidney-From Mechanisms to Clinical Outcome.

Diabetic kidney disease not only has become the leading cause for ESRD worldwide but also, highly contributes to increased cardiovascular morbidity and mortality in type 2 diabetes. Despite increased efforts to optimize renal and cardiovascular risk factors, like hyperglycemia, hypertension, obesity, and dyslipidemia, they are often insufficiently controlled in clinical practice. Although current drug interventions mostly target a single risk factor, more substantial improvements of renal and cardiovascular outcomes can be expected when multiple factors are improved simultaneously.

Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and Treatment.

An absolute, supraphysiologic elevation in GFR is observed early in the natural history in 10%-67% and 6%-73% of patients with type 1 and type 2 diabetes, respectively. Moreover, at the single-nephron level, diabetes-related renal hemodynamic alterations-as an adaptation to reduction in functional nephron mass and/or in response to prevailing metabolic and (neuro)hormonal stimuli-increase glomerular hydraulic pressure and transcapillary convective flux of ultrafiltrate and macromolecules. This phenomenon, known as glomerular hyperfiltration, classically has been hypothesized to predispose to irreversible nephron damage, thereby contributing to initiation and progression of kidney disease in diabetes.

The effects of GLP-1 based therapies on postprandial haemodynamics: Two randomised, placebo-controlled trials in overweight type 2 diabetes patients.

Aims: To assess the effects of glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors on postprandial haemodynamics.

Methods: 57 patients with type 2 diabetes (mean±SD age 62.8±6.