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Post by peppy on Jul 15, 2015 8:19:42 GMT -5
Quote from www.pharmacychoice.com/article/the-return-of-inhaled-insulin.cfm "In Type 2 diabetes, Afrezza® was studied to determine its viability as an add-on therapy in addition to oral diabetes medications. The clinical trial examined Afrezza® in combination with oral medication compared to oral medication alone. The group taking Afrezza® had greater diabetes control at the end of the trial period. While this is not a surprising finding, it does confirm its potential use as an add-on therapy for uncontrolled Type 2 diabetics. "
The following are a list of medications used to treat diabetes.
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The status quo was created to look at the drugs presently used to control diabetes.
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Post by peppy on Jul 15, 2015 9:26:36 GMT -5
Metformin Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects (except in special circumstances, see PRECAUTIONS) and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.
packageinserts.bms.com/pi/pi_glucophage_xr.pdf
Attachment DeletedAttachment Deleted ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Have you ever asked yourself, How does metformin reduce hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization? www.ncbi.nlm.nih.gov/pmc/articles/PMC3398862/ Attachment Deleted mild inhibition of the mitochondria respiratory chain. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- In mitochondria, messenger RNA is made. Some Mitochondrial literature www.ncbi.nlm.nih.gov/pubmed/21857155
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Post by peppy on Jul 15, 2015 10:26:21 GMT -5
Avandia www.accessdata.fda.gov/drugsatfda_docs/label/2008/021071s034lbl.pdf Chemically, rosiglitazone maleate is (±)-5-[[4-[2-(methyl-2pyridinylamino)ethoxy]phenyl]methyl]-2,4-thiazolidinedione, (Z)-2-butenedioate (1:1) with a molecular weight of 473.52 (357.44 free base). The molecule has a single chiral center and is present as a racemate. Due to rapid interconversion, the enantiomers are functionally indistinguishable. The structural formula of rosiglitazone maleate is: Attachment Deleted
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Rosiglitazone, a member of the thiazolidinedione class of antidiabetic agents, improves glycemic control by improving insulin sensitivity. Rosiglitazone is a highly selective and potent agonist for the peroxisome proliferator-activated receptor-gamma (PPARγ). In humans, PPAR receptors are found in key target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPARγ nuclear receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In addition, PPARγ-responsive genes also participate in the regulation of fatty acid metabolism. Insulin resistance is a common feature characterizing the pathogenesis of type 2 diabetes. The antidiabetic activity of rosiglitazone has been demonstrated in animal models of type 2 diabetes in which hyperglycemia and/or impaired glucose tolerance is a consequence of insulin resistance in target tissues. Rosiglitazone reduces blood glucose concentrations and reduces hyperinsulinemia in the ob/ob obese mouse, db/db diabetic mouse, and fa/fa fatty Zucker rat. In animal models, the antidiabetic activity of rosiglitazone was shown to be mediated by increased sensitivity to insulin’s action in the liver, muscle, and adipose tissues. Pharmacological studies in animal models indicate that rosiglitazone inhibits hepatic gluconeogenesis. The expression of the insulin-regulated glucose transporter GLUT-4 was increased in adipose tissue. Rosiglitazone did not induce hypoglycemia in animal models of type 2 diabetes and/or impaired glucose tolerance.
Hepatic Effects Liver enzymes should be measured prior to the initiation of therapy with AVANDIA in all patients and periodically thereafter per the clinical judgment of the healthcare professional. Therapy with AVANDIA should not be initiated in patients with increased baseline liver enzyme levels (ALT >2.5X upper limit of normal). Patients with mildly elevated liver enzymes (ALT levels ≤2.5X upper limit of normal) at baseline or during therapy with AVANDIA should be evaluated to determine the cause of the liver enzyme elevation. Initiation of, or continuation of, therapy with AVANDIA in patients with mild liver enzyme elevations should proceed with caution and include close clinical follow-up, including liver enzyme monitoring, to determine if the liver enzyme elevations resolve or worsen. If at any time ALT levels increase to >3X the upper limit of normal in patients on therapy with AVANDIA, liver enzyme levels should be rechecked as soon as possible. If ALT levels remain >3X the upper limit of normal, therapy with AVANDIA should be discontinued. Attachment DeletedAttachment Deleted
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Post by peppy on Jul 15, 2015 12:33:23 GMT -5
GLUCOTROL labeling.pfizer.com/ShowLabeling.aspx?id=579 Attachment Deleted CLINICAL PHARMACOLOGY
Mechanism of Action The primary mode of action of GLUCOTROL in experimental animals appears to be the stimulation of insulin secretion from the beta cells of pancreatic islet tissue and is thus dependent on functioning beta cells in the pancreatic islets. In humans, GLUCOTROL appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which GLUCOTROL lowers blood glucose during long-term administration has not been clearly established. In man, stimulation of insulin secretion by GLUCOTROL in response to a meal is undoubtedly of major importance. Fasting insulin levels are not elevated even on long-term GLUCOTROL administration, but the postprandial insulin response continues to be enhanced after at least 6 months of treatment. The insulinotropic response to a meal occurs within 30 minutes after an oral dose of GLUCOTROL in diabetic patients, but elevated insulin levels do not persist beyond the time of the meal challenge. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs.
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Post by peppy on Jul 15, 2015 12:50:09 GMT -5
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Post by peppy on Jul 15, 2015 14:28:46 GMT -5
Attachment DeletedBYETTA (exenatide) is a synthetic peptide that was originally identified in the lizard Heloderma suspectum. Exenatide differs in chemical structure and pharmacological action from insulin, sulfonylureas (including D-phenylalanine derivatives and meglitinides), biguanides, thiazolidinediones, alpha-glucosidase inhibitors, amylinomimetics and dipeptidyl peptidase-4 inhibitors. Exenatide is a 39-amino acid peptide amide. Exenatide has the empirical formula C184H282N50O60S and molecular weight of 4186.6 Daltons. The amino acid sequence for exenatide is shown below. H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu -Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 BYETTA is supplied for SC injection as a sterile, preserved isotonic solution in a glass cartridge that has been assembled in a pen-injector (pen). www.accessdata.fda.gov/drugsatfda_docs/label/2009/021773s9s11s18s22s25lbl.pdf Glucagon secretion: In patients with type 2 diabetes, BYETTA moderates glucagon secretion and lowers serum glucagon concentrations during periods of hyperglycemia. Lower glucagon concentrations lead to decreased hepatic glucose output and decreased insulin demand. Gastric emptying: BYETTA slows gastric emptying, thereby reducing the rate at which meal-derived glucose appears in the circulation. Food intake: In both animals and humans, administration of exenatide has been shown to reduce food intake. Attachment DeletedAttachment Deleted
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Post by peppy on Jul 15, 2015 14:48:48 GMT -5
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. Concentrations of the active intact hormones are increased by JANUVIA, thereby increasing and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, JANUVIA increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.
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Post by peppy on Jul 15, 2015 15:03:31 GMT -5
Mechanism of Action SYMLIN, by acting as an amylinomimetic agent, has the following effects: 1) modulation of gastric emptying; 2) prevention of the postprandial rise in plasma glucagon; and 3) satiety leading to decreased caloric intake and potential weight loss. Gastric Emptying. The gastric-emptying rate is an important determinant of the postprandial rise in plasma glucose. SYMLIN slows the rate at which food is released from the stomach to the small intestine following a meal and, thus, it reduces the initial postprandial increase in plasma glucose. This effect lasts for approximately 3 hours following SYMLIN administration. SYMLIN does not alter the net absorption of ingested carbohydrate or other nutrients. Postprandial Glucagon Secretion. In patients with diabetes, glucagon concentrations are abnormally elevated during the postprandial period, contributing to hyperglycemia. SYMLIN has been shown to decrease postprandial glucagon concentrations in insulin-using patients with diabetes. Satiety. SYMLIN administered prior to a meal has been shown to reduce total caloric intake. This effect appears to be independent of the nausea that can accompany SYMLIN treatment. www.accessdata.fda.gov/drugsatfda_docs/label/2007/021332s006lbl.pdf
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