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Rosiglitazone
Rosiglitazone (trade name Avandia) is an antidiabetic drug in the thiazolidinedione class. It works as an insulin sensitizer, by binding to the PPAR in fat cells and making the cells more responsive to insulin. It is marketed by the pharmaceutical company GlaxoSmithKline (GSK) as a stand-alone drug or for use in combination with metformin or with glimepiride. First released in 1999, annual sales peaked at approximately $2.5-billion in 2006; however, following a meta-analysis in 2007 that linked the drug's use to an increased risk of heart attack, sales plummeted to just $9.5-million in 2012. The drug's patent expired in 2012. It was patented in 1987 and approved for medical use in 1999. Despite rosiglitazone's effectiveness at decreasing blood sugar in type 2 diabetes mellitus, its use decreased dramatically as studies showed apparent associations with increased risks of heart attacks and death. Adverse effects alleged to be caused by rosiglitazone were the subject of over ...
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GlaxoSmithKline
GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers and acquisitions, merger of Glaxo Wellcome and SmithKline Beecham, which was itself a merger of a number of pharmaceutical companies around the Smith, Kline & French firm. GSK is the tenth largest pharmaceutical company and No. 294 on the 2022 Fortune Global 500, ''Fortune'' Global 500, ranked behind other pharmaceutical companies China Resources, Sinopharm (company), Sinopharm, Johnson & Johnson, Pfizer, Roche, AbbVie, Novartis, Bayer, and Merck & Co., Merck Sharp & Dohme. The company has a primary listing on the London Stock Exchange and is a constituent of the FTSE 100 Index. As of February 2024, it had a Market capitalization, market capitalisation of £69 billion, the eighth largest on the London Stock Exchange. The company developed ...
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Metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome, and is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotic medication. It has been shown to inhibit inflammation, and is not associated with weight gain. Metformin is taken by mouth. Metformin is generally well tolerated. Common adverse effects include diarrhea, nausea, and abdominal pain. It has a small risk of causing low blood sugar. High blood lactic acid level (acidosis) is a concern if the medication is used in overly large doses or prescribed in people with severe kidney problems. Metformin is a biguanide anti- hyperglycemic agent. It works by decreasing glucose production in the liver, increasing the insulin sensitivity of body tissues, and increasing GDF15 s ...
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Thiazolidinedione
The thiazolidinediones , abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used in the treatment of diabetes mellitus type 2 that were introduced in the late 1990s. As of 2024, there are two FDA-approved drugs in this class, pioglitazone and rosiglitazone. Mechanism of action Thiazolidinediones or TZDs act by activating PPARs (peroxisome proliferator-activated receptors), a group of nuclear receptors, specific for '' PPARγ'' (PPAR-gamma, PPARG). They are thus the PPARG agonists subset of PPAR agonists. The endogenous ligands for these receptors are free fatty acids (FFAs) and eicosanoids. When activated, the receptor binds to DNA in complex with the retinoid X receptor (RXR), another nuclear receptor, increasing transcription of a number of specific genes and decreasing transcription of others. The main effect ...
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Antidiabetic Drug
Drugs used in diabetes treat types of diabetes mellitus by decreasing blood sugar level, glucose levels in the blood. With the exception of Insulin (medication), insulin, most GLP-1 receptor agonists (liraglutide, exenatide, and others), and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors. Type 1 diabetes or Diabetes mellitus is an endocrine disorder characterized by hyperglycemia due to autoimmune destruction of insulin-secreting pancreatic beta cells or from variable degrees of insulin resistance and deficiency. Chronic hyperglycemia of diabetes can lead to multiorgan damage, resulting in renal, neurologic, cardiovascular, and other serious complications. The treatment for Type 1 diabetes is insul ...
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Boxed Warning
In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears near the beginning of the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administration specifies that it is formatted with a "box" or border around the text to emphasize its importance. The FDA can require a pharmaceutical company to place a boxed warning. It is the strongest warning that the FDA requires, and signifies that medical studies indicate that the drug carries a significant risk of preventable, serious or even life-threatening adverse effects. Economists and physicians have thoroughly studied the effects of FDA boxed warnings on prescription patterns. It is not necessarily true that a physician and patient will have a conversation about a drug's boxed warning after it is issued. For instance, an FDA-mandated boxed warning decreased rosiglitazone use by 70%, but that still meant 3.8 million people were given th ...
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Pioglitazone
Pioglitazone, sold under the brand name Actos among others, is an anti-diabetic medication used to treat type 2 diabetes. It may be used with metformin, a sulfonylurea, or insulin. Use is recommended together with exercise and diet. It is not recommended in type 1 diabetes. It is taken by mouth. Common side effects include headaches, muscle pains, inflammation of the throat, and swelling. Serious side effects may include bladder cancer, low blood sugar, heart failure, and osteoporosis. Use is not recommended in pregnancy or breastfeeding. It is in the thiazolidinedione (TZD) class and works by improving sensitivity of tissues to insulin. Pioglitazone was patented in 1985, and came into medical use in 1999. It is available as a generic medication. In 2022, it was the 120th most commonly prescribed medication in the United States, with more than 5million prescriptions. It was withdrawn in France and Germany in 2011. Medical uses Pioglitazone is used to lower blood glucose lev ...
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Type 2 Diabetes
Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Other symptoms include increased hunger, having a sensation of pins and needles, and sores (wounds) that heal slowly. Symptoms often develop slowly. Long-term complications from high blood sugar include heart disease, stroke, diabetic retinopathy, which can result in blindness, kidney failure, and poor blood flow in the lower limbs, which may lead to amputations. A sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon. Type 2 diabetes primarily occurs as a result of obesity and lack of exercise. Some people are genetically more at risk than others. Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primar ...
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Type 2 Diabetes Mellitus
Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Other symptoms include increased hunger, having a sensation of pins and needles, and sores (wounds) that heal slowly. Symptoms often develop slowly. Long-term complications from high blood sugar include heart disease, stroke, diabetic retinopathy, which can result in blindness, kidney failure, and poor blood flow in the lower limbs, which may lead to amputations. A sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon. Type 2 diabetes primarily occurs as a result of obesity and lack of exercise. Some people are genetically more at risk than others. Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primarily ...
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CYP2C8
Cytochrome P4502C8 (CYP2C8) is a member of the cytochrome P450 mixed-function oxidase system involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-chain polyunsaturated fatty acids, e.g. arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and linoleic acid to their biologically active epoxides. Ligands Following is a table of selected substrates, inducers and inhibitors of 2C8. Inhibitors of CYP2C8 can be classified by their potency, such as: * Strong inhibitor being one that causes at least a five-fold increase in the plasma AUC values, or more than 80% decrease in clearance. * Moderate inhibitor being one that causes at least a two-fold increase in the plasma AUC values, or 50-80% decrease in clearance. * Weak inhibitor being one that causes at least a 1.25-fold but less than two-fold increase in the plasma AUC values, or 20-50% decrease in clearance. Retrieved on July 2011 ...
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Beecham Group
The Beecham Group plc was a British pharmaceutical company. It was once a constituent of the FTSE 100 Index. Founded by Thomas Beecham who opened the first factory in St Helens, Lancashire in 1859, Beecham focused on marketing the business by advertising in newspapers and using a network of wholesale agents in northern England and in London, rapidly building up the business. In August 1859 he created the slogan for Beecham's Pills: "Worth a guinea a box", considered to be the world's first advertising slogan, which helped the business become a global brand. Beecham, after having merged with American pharmaceutical company SmithKline Beckman to become SmithKline Beecham, merged with Glaxo Wellcome to become GlaxoSmithKline (GSK). GSK (and later, Haleon) still uses the Beechams brand name in the UK for its over-the-counter cold and flu relief products. Early history Beecham began as the family business of Thomas Beecham (1820–1907). (Beecham would become the grandfathe ...
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Annals Of Internal Medicine
''Annals of Internal Medicine'' is an academic medical journal published by the American College of Physicians (ACP). It is one of the most widely cited and influential specialty medical journals in the world. ''Annals'' publishes content relevant to the field of internal medicine Internal medicine, also known as general medicine in Commonwealth nations, is a medical specialty for medical doctors focused on the prevention, diagnosis, and treatment of diseases in adults. Its namesake stems from "treatment of diseases of ... and related sub-specialties. ''Annals'' publishes a wide variety of original research, review articles, practice guidelines, and commentary relevant to clinical practice, health care delivery, public health, health care policy, medical education, ethics, and research methodology. In addition, the journal publishes personal narratives that convey the feeling and the art of medicine. Selected articles in the journal are freely available; these include pat ...
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Cochrane Collaboration
Cochrane is a British international charitable organisation formed to synthesize medical research findings to facilitate evidence-based choices about health interventions involving health professionals, patients and policy makers. It includes 53 review groups that are based at research institutions worldwide. Cochrane has over volunteer experts from around the world. The group conducts systematic reviews of healthcare interventions and diagnostic tests and publishes them in the Cochrane Library. While Cochrane reviews typically focus on randomized controlled trials, some reviews, particularly in areas such as public and occupational health, also incorporate other study designs. These may include non-randomised observational studies as well as controlled before–after (CBA) studies and interrupted time-series studies. According to the Library, articles are available via one-click access, though some may require registration or a subscription. History Cochrane, previo ...
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