GLP1, kidney

Immune cells and other cells respond to nutrient deprivation by the classic catabolic pathway of AMPK (Adenosine monophosphate kinase). This kinase is a pivotal regulator of glucose and fatty acids metabolism, although current evidence highlights its role in immune regulation. Indeed AMPK, through activation of Foxo1 (Forkhead box O1) and Foxo3 (Forkhead box O3), can regulate FOXP3, the key gene for differentiation and homeostasis of Tregs (T regulators lymphocytes). The relevance of Tregs in the onset of T1D (Type 1 diabetes) is well-known, while their role in the pathogenesis of T2D (Type 2 diabetes) is not fully understood yet...

PURPOSE OF REVIEW: The purpose of this review is to summarize the latest evidence on the prevention and progression of diabetic kidney disease (DKD), as well as novel pharmacological interventions from preclinical and early clinical studies with promising findings in the reduction of this condition's burden. RECENT FINDINGS: We will cover the latest evidence on the reduction of proteinuria and kidney function decline in DKD achieved through established renin-angiotensin-aldosterone system (RAAS) system blockade and the more recent addition of SGLT2i, nonsteroidal mineralocorticoid receptor antagonists (MRAs) and GLP1-RA, that combined will most likely integrate the mainstay for current DKD treatment...

OBJECTIVE: Despite demonstrating improvements in cardiovascular disease, kidney disease, and survival outcomes, guideline-directed antihyperglycemic medications such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like-peptide-1 receptor agonists (GLP1-RA), are underutilized. Many obstacles constrain their use including lack of systematic provider and patient education, concern for medication side effects, and patient affordability. METHODS: We designed a multimodality, systems-based approach to address these challenges with the goal of increasing medication utilization across the largest healthcare system in New York State...

OBJECTIVE: Dutch diabetes guidelines have been updated to incorporate specific therapies with cardiovascular and kidney outcomes benefit in type 2 diabetes patients (T2D) at very high risk for cardiorenal complications. This is part of a comprehensive approach to reduce the risk of diabetes-related complications, including management of glycemia, blood pressure, and lipids. The current study examines the prevalence of T2D at very high cardiorenal risk and the deployment of evidence-based approaches to lower this risk...

The prevalence of obesity in the United States and across the world continues to climb, imparting increased risk of chronic disease. This impact is doubly felt in nephrology because obesity not only increases the risk of chronic kidney disease (CKD) but also exacerbates existing cardiovascular morbidity and mortality. The role of medical weight loss therapy in CKD has been debated, but increasing evidence suggests that intentional weight loss is protective against adverse kidney and cardiovascular outcomes...

Glucagon-like peptide-1 receptor agonists (GLP1RA) are incretin agents initially designed for the treatment of type 2 diabetes mellitus but because of pleiotropic actions are now used to reduce cardiovascular disease in people with type 2 diabetes mellitus and in some instances as approved treatments for obesity. In this review we highlight the biology and pharmacology of GLP1RA. We review the evidence for clinical benefit on major adverse cardiovascular outcomes in addition to modulation of cardiometabolic risk factors including reductions in weight, blood pressure, improvement in lipid profiles, and effects on kidney function...

Obesity is recognized as a true chronic disease and an independent risk factor for kidney disease. In particular, a correlation was observed between obesity and the development of focal segmental glomerulosclerosis. The clinical consequences of obesity on the kidney can include albuminuria, nephrotic syndrome, nephrolithiasis, and increased risk of development and progression of renal failure. Conventional therapy, which includes low-calorie diet, exercise, lifestyle changes, and drug therapy, including GLP1-RA, phentermine, phentermine/topiramate, bupropion/naltrexone, orlistat, is not always able to achieve the desired results and above all does not guarantee stabilization of body weight over time...

Chronic kidney disease (CKD) patients are at increased risk of cardiovascular disease, which is the leading cause of mortality among this population. In addition, chronic kidney disease is a major risk factor for the development of coronary artery disease (CAD) and is widely regarded as a coronary artery disease risk equivalent. Medical therapy is the cornerstone of coronary artery disease management in the general population. However, there are few trials to guide medical therapy of coronary artery disease in chronic kidney disease, with most data extrapolated from clinical trials of mainly non-CKD patients which were not adequately powered to evaluate this subgroup...

The management of diabetes and renal failure is changing thanks to the appearance of new drugs such as glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter type 2 inhibitors (SGLT2i) that have benefits in terms of survival and cardiorenal protection. Based on the potential mechanisms of GLP1-RA, kidney transplant recipients (KTRs) could benefit from their effects. However, high-quality studies are needed to demonstrate these benefits, in the transplant population, especially those related to cardiovascular benefits and renal protection...

IMPORTANCE: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). However, testing for albuminuria among patients with T2D is substantially underutilized in clinical practice; many patients with CKD go unrecognized. For patients with T2D at high cardiovascular risk, or with established CVD, the glucagon-like peptide-1 receptor agonists (GLP1-RA) have been shown to reduce ASCVD in cardiovascular outcome trials, while potential kidney outcomes are being explored...

T2DM (type 2 diabetes mellitus) is a chronic and progressive illness with high morbidity and death rates. Oral semaglutide (Rybelsus®) is a combination of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), and sodium N- (8- [2-hydroxybenzoyl] amino) caprylate (SNAC), an absorption enhancer that facilitates semaglutide absorption across the gastric epithelium in a concentration-dependent manner. This family of drugs apart from glucose lowering effects causes significant weight loss with lower risk of hypoglycemia, and some of them have been linked to a significant reduced major adverse cardiovascular events...

Chronic kidney disease (CKD) is associated with increased morbidity and mortality, especially from cardiovascular (CV) causes, and especially in people with diabetes mellitus (DM). Already the presence of DM increases CV risk and potentiates the risk of CKD. Therefore, besides glycemic control, prevention and treatment of CKD to slow its progression are of clinical importance. A significant nephroprotective effect of novel antidiabetic drugs, namely sodium-glucose cotransporter 2 inhibitors (SGLT2-I) and glucagon-like peptide 1 receptor agonists (GLP1-RA), has been shown on top of their glucose-lowering effects and was confirmed in cardiovascular outcome trials...

Tirzepatide is a twincretin recently approved to improve glycemic control in type 2 diabetes mellitus (T2DM). More specifically, tirzepatide is an agonist of both the glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide-1 (GLP1) receptors. In recent clinical trials in persons with obesity or overweight with associated conditions, tirzepatide decreased body weight and other cardiorenal risk factors (blood pressure, low-density lipoprotein cholesterol, glycated hemoglobin and albuminuria)...

BACKGROUND: A precision medicine approach in type 2 diabetes requires identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy. METHODS: We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes...

As diabetes mellitus becomes increasingly prevalent globally, so does diabetic nephropathy, a complication leading to one of the world's leading causes of end-stage renal disease (ESRD). Current research has linked an increase in the urine albumin-to-creatinine ratio (UACR), a marker for kidney damage, to a greater risk of adverse renal outcomes and ESRD in patients with diabetes. Of the diabetes medications studied and implemented in clinical settings, glucagon-like peptide-1 receptor agonist (GLP1-RA) drugs have been shown to not only help control HbA1c in diabetes but have also demonstrated numerous cardiovascular, hepatic, and renal benefits...

BACKGROUND: There is a lack of consensus on prescribing alternatives to initial metformin therapy and intensification therapy for type 2 diabetes mellitus (T2DM) management. This review aimed to identify/quantify factors associated with prescribing of specific antidiabetic drug classes for T2DM. METHODS: Five databases (Medline/PubMed, Embase, Scopus, Web of Science) were searched using the synonyms of each concept (patients with T2DM, antidiabetic drugs and factors influencing prescribing) in both free text and Medical Subject Heading (MeSH) forms...

Cardiovascular disease remains one of the most prominent global health problems and has been demonstrated to disproportionally affect certain communities. Despite an increasing collective effort to improve health inequalities, a multitude of disparities continue to affect cardiovascular outcomes. Among the most prominent disparities within cardiovascular disease prevention are with the use and distribution of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists...

The antioxidant activities of seven degraded products (GLPs) with different molecular weights ( M w ) of polysaccharides from Gracilaria lemaneiformis were compared. The M w of GLP1-GLP7 were 106, 49.6, 10.5, 6.14, 5.06, 3.71 and 2.42 kDa, respectively. The results show that GLP2 with M w = 49.6 kDa had the strongest scavenging capacity for hydroxyl radical, DPPH radical, ABTS radical and reducing power. When M w < 49.6 kDa, the antioxidant activity of GLPs increased with the increase in M w , but when M w increased to 106 kDa, their antioxidant activity decreased...

Type 2 diabetes mellitus (T2DM) is closely associated with other pathologies, which may require complex therapeutic approaches. We aim to characterize the clinical and pharmacological profile of T2DM patients admitted to an emergency department. Patients aged ≥65 years and who were already using at least one antidiabetic drug were included in this analysis. Blood glycemia, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hemoglobin were analyzed for each patient, as well as personal pathological history, diagnosis(s) at admission, and antidiabetic drugs used before...

The therapeutic benefits of the incretin hormone, glucagon-like peptide 1 (GLP1), for people with type 2 diabetes and/or obesity, are now firmly established. The evidence-base arising from head-to-head comparative effectiveness studies in people with type 2 diabetes, as well as the recommendations by professional guidelines suggest that GLP1 receptor agonists should replace more traditional treatment options such as sulfonylureas and dipeptidyl-peptidase 4 (DPP4) inhibitors. Furthermore, their benefits in reducing cardiovascular events in people with type 2 diabetes beyond improvements in glycaemic control has led to numerous clinical trials seeking to translate this benefit beyond type 2 diabetes...