exenatide and Kidney-Failure--Chronic

Glucagon-like peptide 1(GLP-1) receptor agonists are used in patients with type 2 diabetes as hypoglycemic drugs; a growing body of evidence has clarified their renoprotective benefits. We performed a meta-analysis to summarize the most recent evidence on the renal benefits of GLP-1 receptor agonists from clinical trials of patients with type 2 diabetes.. This meta-analysis used a fixed-effects model to estimate the risk ratio (RR) with 95% confidence intervals (CIs) to investigate the effect of GLP-1 receptor agonists on the renal protection. The outcomes were a composite renal outcome, estimated glomerular filtration rate (eGFR) decrease, new macroalbuminuria, doubling of serum creatinine, end-stage renal disease (ESRD) and renal death. We also checked the composite renal outcome of the patient subgroups based on the structural source of human GLP-1 or exendin-4.. Among the 12 articles screened, seven studies involving 48101 patients met pre-specified criteria and were included. In general, the use of GLP-1 receptor agonists reduced the risk of the composite renal outcome by 17% (RR 0·83 [95% CI 0·79-0·88]; P < 0·00001), with no significant interaction in subgroups analysis (P = 0.66); the risk of new-onset of persistent macroalbuminuria was reduced by 25% (RR 0·75 [95%CI 0·69-0·81]; P < 0·00001) compared to placebo. However, GLP-1 receptor agonists had no significant effect on eGFR decrease (RR 0·92 [95% CI 0·83-1.01]; P = 0·09), doubling of serum creatinine (RR 0·97 [95% CI 0·78-1.21]; P = 0·79), or end-stage renal disease (RR 0·81 [95% CI 0·62-1.06]; P = 0·12) compared to placebo or insulin glargine (AWARD-7) in patients with type 2 diabetes.. GLP-1 receptor agonists, regardless of their structural homology, have significant benefits in reducing the risk of the composite renal outcome, especially in new macroalbuminuria compared with placebo or insulin glargine in patients with type 2 diabetes.

Topics: Creatinine; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Insulin Glargine; Kidney Failure, Chronic

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The development and progression of DN might involve multiple factors. Connective tissue growth factor (CCN2, originally known as CTGF) is the one which plays a pivotal role. Therefore, increasing attention is being paid to CCN2 as a potential therapeutic target for DN. Up to date, there are also many drugs or agents which have been shown for their protective effects against DN via different mechanisms. In this review, we only focus on the potential renoprotective therapeutic agents which can specifically abolish CCN2 expression or nonspecifically inhibit CCN2 expression for retarding the development and progression of DN.

Topics: Animals; Anthocyanins; Antibodies, Monoclonal; Connective Tissue Growth Factor; Diabetes Mellitus; Diabetic Nephropathies; Disease Progression; Exenatide; Guanidines; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Kidney; Kidney Failure, Chronic; Mice; Mycophenolic Acid; Oligonucleotides, Antisense; ortho-Aminobenzoates; Peptides; Renin-Angiotensin System; rho-Associated Kinases; Spironolactone; Venoms

To evaluate the pharmacokinetics (PK), safety and tolerability of a single exenatide dose in patients with renal impairment (RI).. Exenatide (5 or 10 microg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function [Cockcroft-Gault creatinine clearance (CrCL), number of subjects]: normal (>80 ml min(-1), n = 8), mild RI (51-80 ml min(-1), n = 8), moderate RI (31-50 ml min(-1), n = 7) or end-stage renal disease (ESRD) requiring haemodialysis (n = 8). PK data were combined with four previous single-dose studies in patients with Type 2 diabetes to explore the relationship of exenatide clearance (CLp/F) and CrCL.. Mean half-life for healthy, mild RI, moderate RI and ESRD groups were 1.5, 2.1, 3.2 and 6.0 h, respectively. After combining data from multiple studies, least squares geometric means for CLp/F in subjects with normal renal function, mild RI, moderate RI and ESRD were 8.14, 5.19, 7.11 and 1.3 l h(-1), respectively. Exenatide was generally well tolerated in the mild and moderate RI groups, but not in subjects with ESRD due to nausea and vomiting. Simulations of exenatide plasma concentrations also suggest patients with ESRD should have a propensity for poor tolerability at the lowest available therapeutic dosage (5 microg q.d.).. Since tolerability and PK changes were considered clinically acceptable in patients with mild to moderate RI, it would be appropriate to administer exenatide to these patients without dosage adjustment. However, poor tolerability and significant changes in PK make the currently available therapeutic doses (5 and 10 microg) unsuitable in severe RI or ESRD.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Creatinine; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Exenatide; Female; Humans; Hypoglycemic Agents; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Middle Aged; Peptides; Single-Blind Method; Venoms