Notes

METHODS: Descriptive statistics were provided for change in HbA1c, fasting glucose, weight, and insulin dose, and subjects (%) achieving HbA1c <7%, by baseline HbA1c quartile
Inferential statistical analysis on the effect of baseline HbA1c quartile was performed for change in HbA1c. An analysis of covariance (ANCOVA) model was used to evaluate similarity in change in HbA1c RESULTS: At 26 weeks, in both studies, HbA1c reduction, and proportion of subjects reaching HbA1c <7%, were similar or numerically greater with the GLP-1RAs than glargine for all baseline HbA1c quartiles. Fasting glucose reduction was similar or numerically greater with glargine. Weight decreased with both GLP-1RAs across all quartiles; subjects taking glargine gained weight, more at higher baseline HbA1c. Adverse events were uncommon although gastrointestinal events occurred more frequently with GLP-1RAs.CONCLUSIONS: HbA1c reduction with the GLP-1RAs appears at least equivalent to that with basal insulin, irrespective of baseline HbA1c.

This suggests that liraglutide and exenatide OW may be appropriate alternatives to basal insulin in type 2 diabetes, including when baseline HbA1c is very high (≥9%).Liraglutide inhibits autophagy and apoptosis induced by high glucose through GLP-1R in renal tubular epithelial cells.Military Medical University, Xi'an, Shaanxi, P.R. China.Tubular atrophy and dysfunction is a critical process underlying diabetic nephropathy (DN). Understanding the mechanisms underlying renal tubular epithelial cell survival is important for the prevention of kidney failure associated with glucotoxicity.

Autophagy is a cellular pathway involved in protein and organelle degradation. It is associated with many types of cellular homeostasis and human diseases. To date, little is known of the association between high concentrations of glucose and autophagy in renal tubular cells. In semaglutide injection , we investigated high glucose-induced toxicity in renal tubular epithelial cells by means of several complementary assays, including cell viability, cell death assays and changes in ultrastructure in an immortalized human kidney cell line, HK-2 cells. The extent of apoptosis was significantly increased in the HK-2 cells following treatment with high levels of glucose. In addition, in in vivo experiments using diabetic rats, high glucose exerted harmful effects on the tissue structure of the kidneys in the diabetic rats. Chronic exposure of the HK-2 cells and tubular epithelial cells of nephritic rats to high levels of glucose induced autophagy.

Liraglutide inhibited these effects; however, treatment witht a glucagon-like peptide-1 receptor (GLP‑1R) antagonist enhanced these effects. Our results also indicated that the exposure of the renal tubular epithelial cells to high glucose concentrations in vitro led to the downregulation of GLP-1R expression. Liraglutide reversed this effect, while the GLP-1R antagonist promoted it, promoting autophagy, suggesting that liraglutide exerts a renoprotective effect in the presence of high glucose, at least in part, by inhibiting autophagy and increasing GLP-1R expression in the HK-2 cells and kidneys of diabetic rats.Pi-Sunyer X; SCALE Obesity and Prediabetes Investigators. N Engl J Med. 2015 Oct 29;373(18):1779. N Engl J Med.

2015 Oct 29;373(18):1779-80. N Engl J Med. 2015 Oct 29;373(18):1780.Glucagon-like peptide-1 therapy for youth with type 2 diabetes.Glucagon-Like Peptide-1-Mediated Modulation of Inflammatory Pathways in the Diabetic Brain: Relevance to Alzheimer's Disease.Medical Campus, Mail Stop 8106, 12801 E 17th Ave, Aurora, CO 80045, USA. Neuroinflammation has emerged as an important cause of cognitive decline during aging and in Alzheimer's disease (AD).

Chronic low-grade inflammation is observed in obesity and diabetes, which are important risk factors for AD. Therefore, we examined the markers of inflammation in the brain hippocampal samples of Zucker diabetic fatty (ZDF) rats. Pathway-specific gene expression profiling revealed significant increases in the expression of oxidative stress and inflammatory genes. Western blot analysis further showed the activation of NF-kB, defective CREB phosphorylation, and decreases in the levels of neuroprotective CREB target proteins, including Bcl-2, BDNF, and BIRC3 in the diabetic rat brain samples, all of which are related to AD pathology. As glucagon-like peptide-1 drugs based on glucagon-like peptide-1 (GLP-1) are effective in controlling blood glucose levels in type 2 diabetic patients, we tested the in vivo actions of GLP-1 in the diabetic brain by a 10-wk treatment of ZDF rats with alogliptin, an inhibitor of dipeptidyl peptidase. Alogliptin increased the circulating levels of GLP-1 by 125% and decreased blood glucose in diabetic rats by 59%. Normalization of defective signaling to CREB in the hippocampal samples of treated diabetic rats resulted in the increased expression of CREB targets.

Dual actions of GLP-1 in the pancreatic beta cells and in the brain suggest that incretin therapies may reduce cognitive decline in the aging diabetic patients and also have the potential to be used in treating Alzheimer's patients.Contribution of liraglutide in the fixed-ratio combination of insulin degludec OBJECTIVE: Insulin degludec/liraglutide (IDegLira) is a novel combination of insulin degludec (IDeg) and liraglutide.
Read More: http://en.wikipedia.org/wiki/Glucagon-like_peptide-1