WHO defined diabetes mellitus as “a state ofabsolute or relative insulin deficiency,characterized by hyperglycemia and the risk ofmicrovascular and macrovascular complications.”
Types of DiabetesThere are three main types of diabetes:Type 1 diabetes: results from the bodys failure to produce insulin, and presently requires the person to inject insulin.Type 2 diabetes: results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency.Gestational diabetes: is when pregnant women, who have never had diabetes before, have a high blood glucose level during pregnancy.
Insulin ＆SynthesisFauci AS, Kasper DL, Braunwald E, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th Edition: http://www.accessmedicine.com
Insulin Receptor and Drugs· The insulin receptor is a transmembrane receptor that is activated by insulin.· The main activity of activation of the insulin receptor is inducing glucose uptake.Metformin, sulfonylureas, nonsulfonylurea secretagogues,alpha glucosidase inhibitors, and thiazolidinediones.
common medicines SUs Metformin t1/2: 5h t1/2: 6.2h Side-effect: Hypoglycemia Side-effect: GI system Weight gain Lactic acidosis Metallic taste Acarbose TZDs t1/2: 2h t1/2: 3-7hSide-effect: Hypoglycemia Side-effect: GI symptoms
Victoza®· Helps lower A1C level and lower blood sugar· Helps keep beta cells in pancreas working· Helps lose weight· Easy to use NovoTwist® NovoFine®
In Vitro Assays• Liraglutide was tested for its receptor selectivity in binding and functional assays comprising more than 75 different receptors, ion-channels and drug transporters.• Enhancement of glucose-dependent insulin secretion• Sulfonylureas uncouple the glucose-dependency of GLP-1 induced insulin secretion.
In Vivo Assays• Liraglutide is a potent agonist on cloned GLP-1 receptors from human as well as mouse, rat, rabbit, pig and monkey.• Liraglutide treatment of all animal models of diabetes was characterized by a consistent, acute, and dose-dependent reduction in plasma glucose.
Clinical Data• The efficacy and safety of liraglutide were assessed in five double-blind, randomized, controlled clinical trials involving a total of 3,978 patients with type 2 diabetes.• PhaseⅠ: Liraglutide is reported to produce weight loss and reduce food intake.• Phase Ⅱ: The program was supported by evidence from five phase Ⅱ trials.• Phase Ⅲ: A population pharmacokinetic analysis from the long-term phase 3 Trial 1573 (52-week monotherapy trial).
Outline of Treatment of the FiveLong-term Phase 3 Trials
Conclusion• Diabetes Mellitus is a disease of hyperglycemia• Liraglutide: high effciency, low risk drug• Diet, regular exercises, proper eating habits can reduce diabetes