Class V : Kmt 4 Inhibitors

Type 2 diabetes is an increasingly common endocrine disorder. Therefore, it is characterized by chronic hyperglycemia and results in multiple tissue compartments that include microvascular and macrovascular implications. This article discusses subcutaneous dulaglutide, leading to its approval for type 2 diabetes. Dulaglutide is a recombinant GLP-1 Fc fusion protein that links human GLP-1 analog peptide and a variant of human lgG4 Fc fragment. Thus, an analog of GLP-1 has developed long lasting effects and has proven to be effective in type 2 diabetes. It offers greater convenience to the patient. It consists of DPP-IV that protects GLP-1 analog which is covalently linked to human heavy chain by a small peptide linker.

Everybody knows that obesity is a big factor in developing type-2 diabetes, and that part of coping with this metabolic disorder is lifestyle change. If blood glucose does not go down, then medicines are introduced. Some type-2 diabetics even have to administer insulin in order to keep their blood glucose levels

Glyburide is another generic medication used in the management of diabetes mellitus type 2. Two trade names of this drug are DiaBeta and Glynase. The chemical name is 1-[ [p-[2-(5-chloro-o-anisamido) ethyl]phenyl]-sulfonyl]-3-cyclohexylurea. Doses up to 0.75-12 mg/day can be given as a single dose or divided doses. The circulation of the glyburide is that protein binding is extensive and half-life is 10 hours. It is excreted through the renal and biliary system. Glyburide acts as an oral blood glucose lowering drug. The drugs uses include binding and activating the sulfonylurea receptor 1, which causes depolarization. This results in an increase in intracellular calcium in the cells and stimulation of insulin release. Major drug interactions are noted between glyburide and

There are many classes of medication which help control normal levels of glucose in the body. These medications work in different ways; sulfonylureas and meglitinides increase insulin production in different pathways, Thiazolidinediones increase insulin sensitivity by increasing the number of cells, Incretin mimetics increase insulin production as well as delay gastric emptying, Dipeptidyl Peptidase works in the gut, releasing incretin resulting in a prolonged secretion of insulin and Sodium glucose cotransporter reduces reabsorption of glucose and excreting excess glucose out of the urine (Demler & Rhoads, 2018).

Administration of this type is only once or twice a day. It provides a basal insulin level due to its extended release during a time of fasting. The release impairs glucose production in the liver to help maintain a leveled blood glucose reading. Examples of long lasting insulin include insulin glargine and insulin detemir. (2) Different modifications of insulin’s structure results in the slower absorption and longer duration of action. Researchers used this to develop long lasting insulin to help maintain baseline levels in the body. Insulin glargine has a substitution of glycine for asparagine and the addition of two arginine molecules compared to human insulin. These changes are enough to alter the pH of the insulin. When the insulin is injected subcutaneously it precipitates out forming a bolus. The precipitate slows absorption but extends the duration. These properties are essential when trying to obtain a basal level within the body over a long period of time. Glarine usually lasts 24 hours, which means it only has to be injected once daily. Insulin detemir contains a fatty acid side chain which increases its binding to proteins such as albumin. The binding prolongs the action of the insulin but it must still be administered twice a day.

Considerable advances in the past treatment of type II diabetes include the application of lifestyle intervention and prevention efforts aimed at delaying development of glucose intolerance in order to evade diabetes and the progression of new curricula of glucose in the blood-lowering prescriptions to appendage current treatments (DeFronzo, 2010) (Mazzola, 2012). Presently, the control and maintenance of type II diabetes centres on control of glucose by the decrease of haemoglobin and glucose in the blood (DeFronzo, 2010). Current treatment strategies focus on the progression of therapeutic factors that affect the defects contributing to type II diabetes and thus, provide sustainable glucose control through a delaying of disease development

Diabetes mellitus, commonly known as diabetes, is a metabolic disorder characterized by chronic high blood sugar levels. It is caused by an absolute or functional deficiency of circulating insulin, resulting in an inability to transfer glucose from the bloodstream into tissues where it is needed as fuel (Ahmed, Laing and Yates 2011). The disruption in the metabolism of carbohydrates, fats and proteins interferes with the secretion or action of insulin, which plays a vital role in the metabolism and utilization of energy from the nutrients especially carbohydrates. Insulin is produced in the pancreas and secreted in the gastrointestinal tract in the response to high blood sugar levels after ingestion of a substance (REFERENCE).

Another way that type 2, or non-insulin dependent diabetes can be treated is through the use of a medication called metformin (5). Metformin has French Lilac as an active ingredient, which was used in medieval Europe in the treatment diabetics. Metformin acts primarily in the liver to decrease the hepatic glucose output by sensitizing the liver to insulin (3). It also is able to increase the amount of glucagon-like peptide (3), which is a hormone stimulates the release of insulin and suppresses appetite, in both diabetic and non-diabetic adults (6). One side effect of metformin that can greatly benefit those with type 2 diabetes is that users have a tendency to lose weight since the medication is able to fix the overabundance of insulin in the bloodstream that the desensitized insulin receptors do not receive.

Type 2 diabetes results from a multitude of defects: impaired insulin secretion, insulin resistance, and defects in GLP-1 secretion and action. Prior to the onset and throughout the course of the disease, beta cell function and pancreatic mass deteriorate; causes may be lipotoxicity, glucose toxicity, increased age, genetics, insulin resistance, and incretin deficiency. Insulin resistance takes place in the liver, adipose, and skeletal tissues (1), ultimately leading to decreased peripheral uptake and hyperglycemia. In the liver, lack of insulin action results in gluconeogenesis and glycogenolysis, further potentiating the hyperglycemia. In fat cells, decreased GLUT4 leads to excessive release of free fatty acids and adipocytokines (2). Because

As the incidence of type 2 diabetes is steadily increasing, the demand for treatment options is increasing. Dipeptidyl peptidase-4 inhibitors (DPP-4) are a new class of oral anti-hyperglycemic medications that target the incretin system found in the gut. Evidence has shown that treatment with DPP-4 inhibitors has shown significant reductions in HbA1c and increased pancreatic β-cell function without an increased risk of hypoglycemia. In this document, the pharmacology, clinical efficacy, and incidence of adverse effects will be reviewed in an attempt to target a patient population that would benefit the most from treatment with DPP-4 inhibitors.

Renin inhibitors are effective in treating hypertension because they block the activity of an enzyme secreted within the kidney called renin. Renin inhibitors blocks the activation of angiostensinogen. Without the activation of angiostensinogen, blood vessels will relax and widen. This will cause a decrease in blood pressure. The blood volume decrease as well through the diuretic and natriuretic effects with helps treat hypertension.

Dipeptidyl peptidase-4 inhibitors is a medication which reduces blood glucose by blocking DPP-4, which reduces glucagon production and increases insulin secretion. Side effects include slowed gastric emptying. A systematic review of oral medication found that most guidelines for oral medications

The biguanide class drug, metformin, is the most commonly used drug. Metformin is an antihyperglycemic, and works by lowering blood glucose levels, therefore it is a mean of glycaemic control. Metformin is also an insulin sensitizer, as it is known to reduce insulin resistance and plasma fasting insulin levels.13 The insulin sensitizer effect is thought to be due to its positive effects on insulin receptor expression and tyrosine kinase activity.14 A positive effect on tyrosine kinase is important because the insulin receptor is a part of the tyrosine kinase

Later it gave rise to a new drug Dapagliflozin which acts in the similar way in reducing the blood glucose in the kidney by acting as SGLT-1

Pharmacological interventions used to improve glucose control include both oral glucose lowering agents and injectables including glucose like peptide & insulin. Apart from insulin the choice of available pharmacological interventions to treat diabetics has expanded rapidly over the past decade. Till date, the efficacy & safety of these therapies have not been well documented in people with diabetics & CKD.