ABSTRACT: Dipeptidyl peptidase-4 inhibitors (DPP-4s), also commonly called gliptins, are a relatively new class of drugs for the treatment of type 2 diabetes. These agents work in a unique way to improve insulin secretion from the Beta-cells of the pancreas in response to an increase in blood sugar and simultaneously decrease glucagon output from the alpha-cells of the pancreas, which results in decreased hepatic glucose output.This article narrate different chromatographic (HPLC, HPTLC, UPLC,LC) & different spectrophotometric method (UV) for gliptin class single drug as well as combination with other drug1.
Key Words: Dipeptidyl peptidase-4 inhibitors (DPP-4s), UV, HPLC (High Performance Liquid Chromatography), HPTLC (High Performance Thin Layer Chromatography), UPLC (Ultra
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Incretins help the body produce more insulin only when it is needed and reduce the amount of glucose being produced by the liver when it is not needed. These hormones are released throughout the day and levels are increased at meal times2.
The change in glucagon correlates linearly with improvement in glucose tolerance. Since these drugs improve insulin secretion in response to an increase in blood glucose, it seems appropriate to pair them with drugs that have a different mechanism of action, such as insulin sensitizers or Metformin. In fact, improvements in fasting and postprandial glucose levels, improved beta-cell function, and improvement in HbA1c levels have been demonstrated in numerous clinical trials using different gliptins as monotherapy and in combination with various type 2 diabetes medications, including insulin.1
Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) occupy an increasing place in the armamentarium of drugs used for the management of hyperglycemia. It also offer new opportunities for a personalized medicine in patients with Type 2
This article discusses the use of dulaglutide and sitagliptin in the management of type 2 diabetes. Dulaglutide is a recombinant GLP-1 Fc fusion protein, which acts by linking GLP-1 analog peptide and a variant of lgG4 Fc fragments in humans. As such, the analog of GLP-1 has posed effects and has shown elevated efficacies in the management of type 2 diabetes. The primary efficacy in the baseline of HbA was altered during the end of 52nd week. The objective of secondary efficacy included a change in HbA during the end of the 26th and 104th week. The percentage of patients achieved HbA targets ranged between 7.5% to 6.5% in a central laboratory and the body changed significantly. However, current treatment majorly focuses on increasing
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 increase in the prevalence of type 2 diabetes is causing huge health problem through out the world including developed countries. Mostly people with low income groups are affected in developed countries (Zimmet 2001).The magnitude of the healthcare problem of type 2 diabetes results mainly from its association with obesity and cardiovascular risk factors. Indeed, type 2 diabetes has now been identified as one manifestation of the “metabolic syndrome”, a condition characterised by insulin resistance and associated with a range of cardiovascular factors (Jonathan 2003)
Diabetes is a growing concern and health challenge for the American people (b). Diabetes is a condition in which the body cannot react to insulin appropriately or either cannot produce insulin efficiently (w). “Without a properly functioning insulin signaling system, blood glucose levels become elevated and other metabolic abnormalities occur, leading to the development of serious, disabling complications” (w). There are numerous forms of diabetes amongst the nation, however, there are three main forms of diabetes. Most people have heard of type one diabetes, type two diabetes, and gestational diabetes because they are common. Type two diabetes deals with a resistance to insulin, while
Insulin resistance is the first physiological change occurring in type two diabetes. In these type two diabetic patients, insulin is unable to move glucose into liver, kidney and muscle cells although insulin is able to attach properly to the cell surface receptors. In order to rectify this, most patients with type two diabetes start secreting normal to very high levels of insulin, which can initially overcome this resistance. After a while, the pancreas cannot keep up with this high insulin production and the cells become resistant to glucose intake. Persistent hyperglycemia or high blood glucose levels are not desirable since this causes damage to the beta cells of the pancreas that produces the insulin hormone. This damage to beta cells further hampers insulin synthesis and patients at this stage are categorized as full-blown diabetic. Such patients consistently show a hyperglycemia state even after hours of fasting ( Hinkle & Cheever,
It also decreases the amount of sugar absorbed by your intestines and stomach and lowers the level of sugar that is made by the liver as well as helps to maintain it at a normal level. Your metformin medication alone is not likely to contribute to an episode of hypoglycemia however if taken in conjunction with other diabetic medications it could increase your changes so be mindful of the combination of medications which you are taking. Some common side effects is nausea, upset stomach or vomiting and diarrhea other signs of an allergic reaction could be hives, swelling of your face, tongue, lips, and difficulty
Diabetes is a growing but preventable health concern in the United States.1 It is a problem in the body where blood glucose levels rise higher than normal.1 According to the facts released by the American Diabetes Association in 2013, 25.8 million Americans (8.3%) have diabetes 2 and approximately 90% of all cases of diabetes worldwide are considered type 2 diabetes.3 Type 2 diabetes is a progressive disease where the body cannot use insulin properly and the patient ends up using an oral hypoglycemic agent.1 One of the many classes of medications to help manage diabetes is sulfonylureas, including glyburide and glipizide. These drugs close K-ATP channels on Beta cell membranes and cause the pancreas to release more insulin to lower blood sugar.4 Both glipizide and glyburide are metabolized in the liver5, have high protein binding5, and can decrease hemoglobin A1c (HbA1c) up to 1%-2%.6 According to the Health Insurance Association of America, health insurance is defined as "coverage that provides for the payments of benefits as a result of sickness or injury".7 Insurance companies always strive to achieve their target glycemic goal via the most effective and cost effective therapeutic strategy.8 A literature search was conducted to find data on the benefits of converting patients from glyburide to glipizide to find out why insurance prefers the switch.
Diabetes has become a widespread epidemic, primarily because of the increasing prevalence and incidence of type 2 diabetes. Diabetes is an endocrine disease in which the body has either a shortage of insulin or a decrease ability to use insulin or both. Insulin is a hormone that allows glucose to enter the cells and be converted into energy. Diabetes can be characterized as a prevailing, incapacitating, and deadly disease. There are a number of risk factors that increase a person’s tendency toward developing type II diabetes. Modifiable risk factors include obesity, physical inactivity and poor dietary habits are just a few. The
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).
Type 2 diabetes is considered as the most common form of diabetes affecting many individuals. This is a condition that is associated with a high buildup of sugar content in the blood stream. It is accompanied by symptoms such as constant hunger, fatigue, lack of energy and frequent urination. At milder levels, the symptoms become severe and lead to the death of an individual. In the United States, it has been rated as one of the leading causes of death. Importantly, it also increases the rate of the cardiovascular disease once an individual has been reported to have such symptoms. The cardiovascular diseases lead to a greater rate of complications in patients with type two diabetes and hence loss of life. Due to this reason, researchers have focused more on the development of appropriate drugs to enhance treatment of the condition. Importantly, the fact that it is a big challenge to the medical sector critical evaluation of all possible types of treatment is vital. Therefore, the article on “semaglutide and cardiovascular outcomes in patients with type 2 diabetes” offers beneficial knowledge to the healthcare sector.
The endocrine pancreas remains responsive to GLP-1 but unresponsive to GIP in type2 diabetic patient. Incretin effect is describe as the difference in insulin secretion from an oral glucose load in comparison to glucose administered intravenously. It is responsible for 50%- 70% of the total insulin secreted after oral glucose [25]. These peptides have a short half-life, as these are rapidly inactivated by DPP-4 within 1½ min.
DPP-4 inhibitors medications work by helping to reduce glucose levels, but generally not a lot. A positive however is they don't cause weight gain. These medications include Sitagliptin, Saxagliptin and Linagliptin.
Reactive hypoglycemia, a rare form of hypoglycemia, increases insulin levels after the consumption of excess carbohydrates, leading to a drop in blood glucose levels. This differs from conventional hypoglycemia where blood glucose drops several hours after a meal, but can easily be returned to normal by the consumption of food. Reactive hypoglycemia can cause fatigue, dizziness, shakiness, and in extreme cases, a coma. Although no effective treatments exist, glucagon, a peptide hormone derived from pancreatic alpha cells, seems to reduce symptoms. In the proposed experiment, the effectiveness of glucagon relative to a regimen of dietary control, exercise, and Acarbose will be tested on Zucker-diabetic-fatty (ZDF) rats (Rattus rattus). Three
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.
Diabetes is a systemic disease caused by a decrease in the secretion of insulin or reduced sensitivity or responsiveness to insulin by target tissue. (Beale, et al., 2011) The incidence of diabetes is growing rapidly in the United States and worldwide. An estimated 347 million people around the world are afflicted with diabetes. (Whalen, et al., 2012) According to World Health Organization (WHO), Diabetes prevalence among adults over 18 years of age has risen from 4.7% in 1980 to 8.5% in 2014. It is the major cause of blindness, kidney failure, heart attack, stroke and limbic amputation. World Health Organization (WHO) projects that diabetes will be the 7th leading cause of death in 2030. It is a complex and costly disease that can affect nearly every organ in the body and result in devastating consequences. The leading cause of non-traumatic lower extremity amputations, renal failure, and blindness in working-age adults, diabetes is also a major cause of premature mortality, stroke, cardiovascular disease, peripheral vascular disease, congenital malformations, perinatal mortality, and disability. (Cefalu, 2000) Insulin therapy and oral hypoglycemic agents have demonstrated improvement in glycaemic control. However, Insulin therapy has some disadvantages such as ineffectiveness following oral administration, short shelf life, of the need for constant refrigeration, and fatal hypoglycaemia, in the event of excess dosage.