-Their-mechanism-of-action-is-to-increase-insulin-secretion-decrease-glucagon-release-reduce-food-intake-and-slow-gastric-emptying-k

They target postprandial blood glucose values and have some effect on fasting levels as well. In addition, they promote weight loss and may help to preserve β-cell function, both major problems in T2DM patients. semaglutide mechanism of action in hemoglobin A1c are similar to those produced by other T2DM agents, including thiazolidinediones, low-dose metformin, and sulfonylureas, and better than those caused by α-reductase inhibitors and dipeptidyl peptidase-4 inhibitors. These agents have been safely studied in combination with metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin therapy. Overall, data are limited for head-to-head comparisons, but it appears that liraglutide may have better efficacy and tolerability compared with exenatide; however, more studies are needed. They are overall well tolerated, with the main adverse events being similar to those with metformin (gastrointestinal intolerances that are transient and dose dependent).

However, patients must be monitored for pancreatitis as a rare but possible side effect. For is semaglutide safe to use an injectable agent, exenatide and liraglutide offer another therapeutic option to control hyperglycemia with the potential for weight loss and may be SGLT-2 INHIBITION ADDED TO GLP-1 AGONIST THERAPY FOR TYPE 2 DIABETES: WHAT IS Endocr Pract. 2015 21(12):1315-22.Antiobesity therapeutics with complementary dual-agonist activities at glucagon and glucagon-like peptide 1 receptors.Technology (DGIST), Daegu, Republic of Korea.AIM: To develop more effective and long-lasting antiobesity and antidiabetic therapeutics by employing novel chemical modifications of glucagon-like METHODS: We constructed novel unimolecular dual agonists of GLP-1R and glucagon receptor prepared by linking sEx-4 and native glucagon (GCG) via lysine or triazole [sEx4-GCG(K) and sEx4-GCG(T), respectively] and evaluated their antiobesity and antidiabetic efficacy in the diabetic and obese mouse model.RESULTS: Both sEx4-GCG(K) and sEx4-GCG(T) showed the beneficial metabolic effects of GLP-1 and glucagon: they promoted weight loss and ameliorated insulin resistance and hepatic steatosis.

They also increased thermogenesis in brown adipose tissue, and lipolysis and β-oxidation in white adipose tissue, with concomitant suppression of lipogenesis. Furthermore, both dual agonists activated the 5'-AMP-activated protein kinase signalling pathway and prevented palmitate-induced oxidative stress in skeletal muscle cells.CONCLUSION: Through their complementary dual agonism, sEx4-GCG(T) and sEx4-GCG(K) induce more marked weight loss and metabolic improvements than conventional agonists, and could be developed as novel therapeutic agents for the treatment of obesity and associated metabolic disorders in humans.The endocrine pancreas in non-diabetic rats after short-term and long-term treatment with the long-acting GLP-1 derivative NN2211.Glucagon-like peptide 1 (GLP-1) and GLP-1 receptor agonists increase the beta-cell mass in rodent models of type 2 diabetes and enhance the proliferation rate of beta cells in vitro, while the long-term effect in vivo in non-diabetic animals is unknown. We studied the endocrine pancreas in non-diabetic Sprague-Dawley rats after short- and long-term treatment with NN2211, an acetylated long-acting derivative of GLP-1. Four groups of rats (n=6 for each group) received two daily injections with either NN2211 or vehicle for 1 or 6 weeks.

NN2211-treated rats displayed a 10% lower body weight after both 1 week (p<001) and 6 weeks (p<005) of treatment. The mean beta-cell mass in NN2211-treated rats was increased by 19% after 1 week of treatment (p<05), but normalized after 6 weeks of treatment. No difference in alpha-cell mass, volume-weighted mean islet volume, or pancreas mass was found after 1 or 6 weeks of treatment. We conclude that NN2211 treatment of non-diabetic rats induces a sustained lower body weight, and an only temporary increase in the beta-cell mass, while the alpha-cell mass and the volume-weighted mean islet volume are 10152/ajpendo0565012. Epub 2013 May 28.Intraportal GLP-1 stimulates insulin secretion predominantly through the hepatoportal-pancreatic vagal reflex pathways.We previously reported that glucagon-like peptide-1 (GLP-1) appearance in the portal vein facilitates hepatic vagal afferent activity, and this further augments reflexively the pancreatic vagal efferents in anesthetized rats, suggesting a neuroincretin effect of GLP-1.

To determine whether the GLP-1-induced vagal pathways lead to a neuronal-mediated component (NMC) of insulin secretion, we infused GLP-1 at a physiological or pharmacological dose (1 or 3 pmol·kg(-1)·min(-1), respectively) into the portal vein in conscious rats with selective hepatic vagotomy (Vagox) or sham operation (Sham).