Drugs Used in Controlling Diabetes

Prof. Hadyanto Lim, MD, PhD, FESC, FIBA

Department of Pharmacology and Molecular Science, Faculty of Medicine, Methodist University of Indonesia - Medan Molecular Biology Research, Postgraduate School, University of Sumatra Utara - Medan

Hypoglycemic Agents
Insulin

Oral Antidiabetic

The Characteristics of Type I and Type II DM, Classified by

National Diabetes Data Group in 1979

HLA, Human Leucocyte Antigen

Time course of plasma glucose concentrations, endogenous insulin secretion, and exogenous insulin action

Insulin signaling and action

Metabolic signaling pathway Activation of phosphatidylinositol -3-kinase leads to the movement of glucose transporter (GLU) 4 containing vesicles to the cell membrane, increased glycogen and lipid synthesis, and stimulation of other metabolic pathways.

PDK, phospholipid-dependent kinase PKB/Akt, protein kinase B GSK3, glycogen synthase kinase GS, glycogen synthase; P, inactive phosphorylated form; UDPG, uridine diphosphate glucose dehydrogenase

Pharmacokinetic Profiles of Insulin

Oral Antidiabetic Drugs

Hypoglycemic Drugs - Sulfonylurea drugs
- Meglitinide drugs - Rapaglinide (Prandin) - Nateglinide (Starlix) Antiglycemic Drugs Metformin Thiazolidinediones - Pioglitazone (Actos) - Rosiglitazone (Avandia) -Glucosidase Inhibitors - Acarbose (Precose) , - Miglitol (Glyset)

Therapeutic effects of Diet, Exercise, and Oral Drugs used in the treatment of patients with type II DM

Mechanism of Action of Oral Hypoglycemic Agents

GLUT-2, Glucose transpoter KIR inwardly rectifying K+ channel TCA, tricarboxylic acid

Minneman KP, Wecker L. Brodys Human Pharmacology. 2005

Pharmacologic Properties of Oral Antidiabeic Drugs

Brenner GM, Stevens CW. Pharmacology 2006

Effects of Oral Antidiabetic Drugs

FPG, Fasting Plasma Glucose Concentration Brenner GM, Stevens CW. Pharmacology 2006 PPG, Postprandial glucose concentration HBA1c , Glycosylated hemoglobin conc.

Cumulative Incidences of Events, According to Glucose-Control Strategy

Patel A. et al. The ADVANCE collaborative Group N Engl J Med 2008; 358: 2560-72

P = 0.16

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group

Median glycated hemoglobin level of 8.1% Intensive therapy (targeting a glycated hemoglobin level below 6.0%) or Standard therapy (targeting a level from 7.0 to 7.9%).

P = 0.04

N Engl J Med 2008;358:2545-2559