DPP-4 Enhances The Body: A Case Study

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

Incretin based drugs have proven to be effective glucose-lowering agents (Butler et al, 2013). But there have been concerns with respect to the long-term consequences of using such therapies. The issues raised were regarding their causal relationship with acute pancreatitis (AP). There are clearly conflicting evidence that have been presented in preclinical studies and in epidemiologic studies which suggest an association which may or may not be a causal relationship between these drugs and AP. (Butler et al, 2013)

The clinical study outcome showed that insulin degludec compared similarly with insulin glargine in both type 1 and type 2 diabetic patients on the reductions of both HbA1c and fasting plasma glucose levels. However, when the amount of episodes of hypoglycemia were compared, the patients taking insulin degludec showed an increased reduction of hypoglycemic events, anywhere from 18% to 25% fewer incidences (Stockley, 2014, p. 18). This finding is extremely important and beneficial because the main reason cited for

Prescription drugs are a major life factor to both young and old in our society. The vast variety of drugs used to treat many medical conditions is endless. Firstly, glyburide (Diabeta) is an oral diabetes medicine that helps control blood sugar levels. Diabeta is the trade name for glyburide; similarly glyburide is the generic name for Diabeta. Glyburide (Diabeta) is of the sulfonylurea class (hypoglycemic agents) which treats type two diabetes (Sorrentino, 2013). Because of glyburide medications, the pancreas releases more insulin into the blood stream. In type two diabetes, the body is unable to store excess sugar, and therefore, this sugar remains in the bloodstream (Web MD, 2013).

Invokana is an SGLT2 (Sodium-glucose co-transporter 2 ) inhibitor, which is a failrly new class of drugs. SGLT2 is a low-affinity, which is located in the proximal tubule in the kidneys, is a high capacity glucose transporter within the body and is responsible for 90% of glucose reabsorption. (Joffe, 2013) Inhibition of this protein can cause a decrease in blood glucose due to the increase in renal glucose excretion. (Joffe, 2013) It offers extra glucose control by allowing the body to have increased insulin sensitivity and an increase in uptake of glucose in the muscle cells, also decreased gluconeogenesis and improved first phase insulin release from the beta cells. (Joffe,

Prevention and slowing the progression of DPN via glucose control has been demonstrated to be effective in patients with type 1 diabetes, but may not be as effective in patients with type 2 diabetes (Callaghan BC 201211). Other studies found no correlation between glycated hemoglobin (HbA1C) with mean of 6.9% and the severity of DPN (Owolabi MO 201212). Diabetic patients are more susceptible to dyslipidemia and metabolic syndrome. Those patients have body mass index (BMI) ≥30Kg/m2, abnormal glucose metabolism with insulin resistance, high low-density-lipoprotein (LDL), total cholesterol (TC), triglycerides (TG), and low high-density lipoprotein (HDL). Those abnormal findings expose patients to atherosclerotic changes and microvascular complications together with hypertension and cardiovascular diseases (Mooradian AD

(2011), Metformin, a biguanide, is the most popular first-line type 2 diabetes due to its mechanism of action commonly used to reduce hepatic glucose production. It is normally considered as weight-neutral with chronic use and also does not increase the risk of hypoglycemia. There may be some cardiovascular benefits from this drug but there is no strong clinical trial data (Inzucchi et al. 2012).

Due to its insulin-independent mechanism of action that produces glucose excretion in the urine, dapagliflozin was known to be very effective when utilized as monotherapy, plus complementary and effective when used in combination with other anti-diabetic drugs; the clinical trial program was aimed to discover this therapeutic potential. Also, the program discovered the persistent calories loss in the

Thiazolidinediones or glitazone are a class of oral antidiabetic agents. Thiazolidinediones are a synthetic ligand for the peroxisome proliferator-activated receptor g (PPARg). Troglitazone was the first thiazolidinedione antidiabetic agent that approved for the clinical use by the US in 1997. Troglitazone decreased hepatic glucose production, lowers blood glucose levels through increased glucose uptake by skeletal muscle, and increased insulin sensitivity of the target tissue in animal models of metabolic impairment. These pharmacological effects are exerted through the PPARg-dependent transcription of genes which involved in glucose and lipid metabolism and also in energy homeostasis. Troglitazone represents a model of an idiosyncratic

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

Insulin therapy, however; should be reserved for patients who have failed on an adequate trial of diet, exercise, and oral anti-diabetic drugs. Insulin administration significantly reduces glucose concentrations by suppressing hepatic glucose production, increasing postprandial glucose utilization, and improving the abnormal lipoprotein composition commonly seen in patients with insulin resistance. Insulin therapy may also decrease or eliminate the effects of glucose toxicity by reducing hyperglycemia to improve insulin sensitivity and β-cell secretory function. It suppresses ketosis and helps in delaying or arresting diabetic complications (Katzung ,2004 and Kumar, 2006).

The VDRs are the most commonly targeted receptors in this class, by 8% of all NHR-targeting drugs. PPARs are involved in the regulation of gene expression in lipid and lipoprotein metabolism, inflammation, and glucose homeostasis. Due to their diversity of potential therapeutic actions, they are attractive targets for the development of oral drugs for metabolic syndromes such as cardiovascular diseases and type 2 diabetes. PPAR-α agonists, which make up 3% of all NHR-targeting drugs, belong to the fibrate class of drugs (bezafibrate, ciprofibrate, fenofibrate, gemfibrozil). These drugs act by increasing high-density lipoprotein (HDL) levels and decreasing triglyceride levels. The PPAR-γ agonist pioglitazone is an antidiabetic drug that increases insulin sensitivity and glucose

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.

Oral anti diabetic agents are used as pharmacotherapy options mainly for type 2 diabetes patients or as an adjuvant therapy for type 1 diabetes patients, who need an oral agent along with insulin/insulin analogues for better glycemic control. There are a wide variety of oral anti diabetic drug classes that are available. The choice of pharmacotherapy is patient specific and usually a stepped therapy approach is applied and titrated as per individual patient requirements. The article here is a detailed overview of the different classes of these oral agents, their pharmacology, comparative efficacy, efficacy results from clinical trials, general recommendations etc.