New treatment for Diabetes Mellitus and Drugs to treat Hypoglycemia
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New treatment for Diabetes Mellitus and Drugs to treat Hypoglycemia

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This ppt covers recently FDA approved treatment of DM and other drugs that are in clinical pipelines or still under consideration. 2nd portion of ppt covers protocol used to treat hypoglycemia in ...

This ppt covers recently FDA approved treatment of DM and other drugs that are in clinical pipelines or still under consideration. 2nd portion of ppt covers protocol used to treat hypoglycemia in different situations.

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New treatment for Diabetes Mellitus and Drugs to treat Hypoglycemia New treatment for Diabetes Mellitus and Drugs to treat Hypoglycemia Presentation Transcript

  • New Treatment For Diabetes Mellitus Drugs To Treat Hypoglycemia Faraza Javed Mphil Pharmacology
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Diabetes Mellitus Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Treatment  Synthetic Amylin Analog  Incretin Mimetics  Oral Agents Insulin Sectretagogues Alpha Glucosidase Inhibitors Dipeptidyl Peptidase IV Inhibitors Insulin Sensitizers
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Synthetic Amylin Analog • Pramlintide, a synthetic analogue of amylin, is an injectible antihyperglycemic agents that modulates postprandial glucose levels and is approved for postprandial use for persons with type 1 and type 2 diabetes. • Pramlintide lowers glucagon during a meal, slows food emptying from the stomach and curbs the appetite.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association • It is administered in addition to insulin who are unable to achieve their target postprandial blood sugar level. • Major adverse effects are hypoglycemia and GI symptoms including nausea, vomiting and anorexia.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Glucagon like Polypeptide- 1 Receptors Agonists • Incretins are intestinal factors that are released in response to nutrients, contributing to blood glucose lowering. • In type 2 Diabetes, the release of glucagon like polypepide is diminished postprandially, which leads to inadequate glucagon suppression and excessive hepatic glucose output.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association • Two synthetic analogues of glucagon likepolypeptide Exenatide and Liraglutide are commercially available to help restore GLP-1 activity. • Exenatide and Liraglutide, along with DPP-4 inhibitors, are currently available to treat patients with T2DM by addressing decreased concentrations of GLP-1.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Insulin Pump Insulin pumps are small computerized devices that deliver insulin in two ways: • In a steady measured and continuous dose (the "basal" insulin) • As a surge ("bolus") dose, at your direction, around mealtime. This FDA Approved Insulin delivery system most closely mimics the body's normal release of insulin.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Combination Therapy • GLP-1 (Glucagon like Polypeptide) Receptor agonist with Insulin Secretagogue or with Insulin. • DPP-4 (Dipeptidyl Peptidase IV) Inhibitor Sitagliptin or Vidagliptin (Glavusmet) in combination with metformin. • Pramlintide in combination with Insulin, Metformin or Sulphonylurea.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Modern Advancement in DM Treatment The current classes of medications are effective initially, but glucose-lowering effects are not typically sustained long term as beta cell dysfunction progresses. Several new classes of medications are currently in development, as well as a new long- acting insulin.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association There are two organizations that are reviewing the DM therapy treatment and encouraging new reasearches: • American Diabetes Association (ADA) • International Diabetes Federation (IDF)
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Sodium Glucose Cotransporter 2 Inhibitors (SGLT-2) SGLT-2, a low-affinity but high-capacity transporter found in the brush border of the proximal tubule, is a mediator of glucose reabsorption in the kidneys. In hyperglycemia, the kidneys may play an exacerbating role by reabsorbing excess glucose, ultimately contributing to chronic hyperglycemia, which in turn contributes to chronic glycemic burden and the risk of microvascular consequences.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association • SGLT-2 inhibitors exert their effects by causing the kidneys to excrete glucose into the urine. The effects are also independent of insulin secretion. • These proposed mechanisms make SGLT-2 a viable target to help combat hyperglycemia in patients with T2DM. These agents decreased A1C anywhere from 0.5 to 1.5%, and demonstrated low incidences of hypoglycemia with minimal side effects.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association SGLT-2 Inhibitors (Phase III) include: • Canagliflozin • Empagliflozin • Dapagliflozin
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Long Acting Basal Insulin Analogue LY2605541 is a long-acting basal insulin analogue that is currently being evaluated in phase III studies in T2DM patients. The primary aim of insulin therapy is to replace endogenous insulin secretion in patients with type 1 or type 2 diabetes in a physiologic manner, mimicking normal secretion patterns to adequately regulate glucose metabolism.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association • The currently available human insulins for basal therapy - neutral protamine Hagedorn (NPH), - and analogs such as insulin glargine, differ in pharmacokinetic properties. • Clinical trial data indicate that insulin glargine may satisfy basal insulin requirements, with an improved safety profile relative to other available insulins used for basal supplementation.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 11-β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors (11-β-HSD1) 11-β-Hydroxysteroid Dehydrogenase or cortison reductase convert cortison to cortisol. Overexpression of this enzyme can lead to obesity insulin resistance.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Preclinical evidence indicates that 11-β-HSD1 has a function in both obesity and metabolic disease in rodents, which suggests that inhibiting this catalyst in liver and adipose tissues may lead to enhanced hepatic and peripheral insulin sensitivity, thus improving overall glucose levels and possibly decreasing overall macrovascular risk.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Vitamin D In DM Recent studies have found that deficiency of Vitamin D results in reduction in insulin secretion and thus in hyperglycemia. Both insulin secretion and sensitivity depends upon intracellular calcium concentration also and Vitamin D is one of the hormone which has been found to regulate calcium flux within the cells. In both observational and case-control studies, an inverse relationship has been reported with level of 25(OH)Vit D and degree of glycemic control.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Stem Cell Therapy A newly created method of placing stem cell-derived pancreatic cells in capsules under the skin to replace insulin is tested in diabetic disease models. The method is successful without producing likely complications. The study confirms the viability of combining stem cells and 'encapsulation' technology to treat insulin-dependent diabetes.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Betatrophin Scientists at Harvard Stem Cell Institute (HSCI) found that a hormone called betatrophin plays a significant role in enhancing the production of insulin by beta cells in mice. If the study also shows similar results in humans, it will be a huge leap forward in the treatment of diabetes.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Islet Cell Transplantation In islet cell transplantation, beta cells are removed from a donor's pancreas and transferred into a person with diabetes.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association • Beta cells are found in the islets of the pancreas and produce insulin, which regulates blood sugar levels. Once transplanted, the donor islets begin to make and release insulin. • As with all organ and tissue transplants, rejection of the donor cells is the greatest challenge.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Brown Fat Transplant May Aid in Diabetes Management There are at least two types of adipose (fat) tissue. • White adipose tissue is the more common type that lies below the skin, stores excess fat in the body, and expands with weight gain. • Brown adipose tissue, on the other hand, is derived from muscle and is highly thermogenic. In other words, it burns energy to produce heat and maintain body temperature in warm-blooded organisms.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association • Unlike white adipose tissue, the quantity of brown fat in the body is inversely proportional to body mass index (BMI), meaning that lean people tend to store more of this type of fat than people that are overweight , leading to the characterization of brown fat as “good” fat.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association • Researchers find out that brown fat transplant had significantly lower body weight, reduced white fat mass, show better sensitivity to insulin, and improved glucose metabolism in labourtary animals. • Now researchers are trying to collect data on humans to evaluate either the study also shows similar results in humans or not.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association The Use of Vanadium Complexes in Diabetes Mellitus Recent researches found that vanadyl ion and its complexes are effective not only in treating or relieving both types of DM but also in preventing the onset of DM. Exact mechanism is still unknown.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Gastric Stimulator DIAMOND, made by the Israeli medical device company MetaCure, is an implantable gastric stimulator with electrodes attached to the outer stomach muscles.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association • Its original purpose was to treat obesity But its developers discovered that in the hundreds of people implanted with DIAMOND worldwide, the device also effectively controls blood glucose levels as well as, or better than, synthetic insulin and other diabetes medications. It also helped improve diabetes- associated conditions such as high blood pressure, cholesterol and triglycerides.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association The Dead Sea The mineral-rich Dead Sea has long been known as a natural treatment for skin, rheumatic and respiratory diseases. According to a study by health sciences researchers at Ben-Gurion University, the salty water also help lower blood glucose levels and could improve the medical conditions of diabetics.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association • After soaking in a pool filled with Dead Sea water for 20 minutes, there was a considerable decrease – up to 13 percent in some cases – in the blood glucose levels. • It’s still a bit early to draw conclusions, but further testing will determine if one day a Dead Sea dunk could be prescribed as a way to lessen the dose of insulin needed.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Hypoglycemia Hypoglycemia is a condition characterized by abnormally low blood glucose (blood sugar) levels, usually less than 70 mg/dl. • Hypoglycemia is not a disease itself – it is the result of an underlying issue or combination of them.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Causes • Drugs e.g. Insulin, Sulphonylurea • Endocrinopathies (Glucagon Deficiency) • Tumor of B cells • Poisoning (ethanol inhibits gluconeogenesis) • Renal Failure
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Mild Symptoms • Trembling/shakiness • Sweating • Anxiety • Irritability • Pallor • Palpitations • Headache
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Severe Symptoms • Concentration problems • Confusion • Irrational and disorderly behavior • Seizures • Loss of consciousness
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Treatment Protocol Initially • Glucose 10-20 g is given by mouth, either in liquid form or as granulated sugar (2 teaspoons) or sugar lumps. • GlucoGel® - formerly known as Hypostop® Gel - may be used. • Repeat capillary blood glucose after 10-15 minutes; if the patient is still hypoglycaemic then the above can be repeated (probably up to 1-3 times).
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 1 1. Mild to moderate hypoglycemia should be treated by oral ingestion of 15 g carbohydrate; glucose or sucrose crystals/ solutions are preferable to orange juice and glucose gels. Patients should retest blood sugar in 15 minutes and retreat with another 15 g of carbohydrates if BG remains <70mg/dl
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 2 2. Severe hypoglycemia in a conscious person should be treated by oral ingestion of 20 g of carbohydrate, preferable as glucose tablets or equivalent. Blood sugar should be retested in 15 minutes, and then retreated with a further 15 g of glucose if BG remains <70 mg/dl.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 3 3. Severe hypoglycemia in an unconscious individual: – No IV access: 1 mg of glucagon should be administered subcutaneously or intramuscularly. – Hypoglycemic effects (specially due to drugs) may persist for 12-24 hours and ongoing glucose infusion or other therapies such as octreotide may be required.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association • With IV access: 10-25 g (20-50 cc of D50W) of glucose should be given intravenously over 1-3 minutes. • Retest in 15 minutes to ensure the BG >70mg/dl and retreat with a further 15 g of carbohydrate if needed. • Once conscious, eat usual snack or meal due at that time of day or a snack with 15 g carbohydrate plus protein.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 4 Prolonged Hypoglycemic Coma: Use IV mannitol and dexamethasone with constant glucose monitoring and IV glucose to keep serum level at 70-80mg/dl until either consciousness has been restored or permanent brain damage is diagnosed.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 3. Once the patient is more alert, carbohydrate should be given, e.g. toast, or a normal meal. For inpatients, an infusion of 10% glucose may be administered if required.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 5 • Patients receiving antihyperglycemic agents that may cause hypoglycemia should be counseled about strategies for prevention, recognition and treatment of hypoglycemia.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association References Katzung Pharmacology, 11th Edition www.idf.org SGC2I in DM Treatmet, Jcem. (2010) vol.95(1) NIDDK, NIH Review (2014) www.diabetes.org.uk CDA clinical practice guidelines ND Cohen, JE Shaw - Internal medicine journal, 2007. C Kelly, NH McClenaghan - Stem cells international, 2011. www.guidelines.diabetes.ca Alexander, G Caleb. (2008). Trends in DM treatment. Archives of internal medicine. 168(19):2088-2094.
  • guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association