Diabetes Mellitus Pharmalogic Treatment
From Ask Dr Wiki
By Nadia Ali M.D, M.B.B.S
Contents |
Biguanides
Metformin is the available agent in this goup. It is the first line treatment used for type 2 diabetes mellitus. The mechanism of actions of this drug are as follows.
- It suppresses hepatic gluconeogenesis.
- It increases insulin sensitivity in peripheral tissues such as skeletal muscles and liver.
- It decreases serum free fatty acids and triglycerides.
- It leads to a modest weight loss in obese individuals.
It causes less hypoglycemia than the other group of Sulphonylureas. The most serious side effect of Metformin is lactic acidosis. Hence it is relatively contraindicated in conditions which predispose to lactic acidosis such as renal insufficiency [Cr > 1.4 in women and >1.5 in men], respiratory insufficiency causing hypoxia, congestive heart failure, reduced tissue perfusion, severe infection, liver disease, alcohol abuse and use of radiographic contrast agents.
Sulfonylureas
This class stimulates the secretion of insulin from the beta cells of the islets of pancreas. They can be used alone or in conjunction with other hypoglycemic medications. The second generation of sulfonylureas are more effective than the first generation and hence commonly used. Glipizide, Glimepride and Gluburide are the examples of the second generation. The main side effect is hypoglycemia and hence caution is required in patients with renal insufficiency, alcohol abuse and other conditions that might exacerbate hypoglycemia.
Meglitinides
This is another class of hypoglycemics that are secretogogues, meaning that they stimulate the release of insulin from pancreas. They are shorter acting than sulfonylureas and are given at mealtimes. The main side effect is hypoglycemia. Repaglinide and [Nateglinide]] are the examples from this class.
Alpha-Glucosidase Inhibitors
Acarbose and Miglitol belong to this group. These hypoglycemics inhibit the intestinal enzyme alpha glucosidase resulting in slower glucose absorption and improved post prandial blood sugars. These can be used in both type 1 and type 2 diabetics. Their main side effect is flatulence and diarrhea.
Lipase Inhibitors
It is an adjunctive treatment for obese type 2 diabetics. Orlistat is the available medication in this class which inhibits intestinal lipases. In doing so it brings about improved blood sugar control. It also causes a reduction in LDL and an elevation in HDL. The main side effects are related to the gastrointestinal tract.
Thiazolidinediones
This group increase glucose uptake and increase insulin sensitivity by binding to peroxisome proliferator-activated receptors PPARγ. PPARγ receptor is located in the adipose tissue as well other peripheral tissues of the body. Rosiglitazone and Pioglitazone act as agonists to the PPARγ receptors. This binding leads to down regulation of cytokines such as resistin which inhibit glucose uptake by the peripheral tissues. Their side effects are weight gain, edema and fluid retention. For the latter two effects they are contraindicted in heart failure. A recent meta analysis concluded that Rosiglitazone is associated with increased risk of death from cardiovascular causes.
Incretin Mimetics
Incretins are intestinal derived factors that increase glucose stimulated insulin secretion. The two incretins are Glucagon-Like Peptide 1 [GLP-1] and Gastric Inhibitory Peptide [GIP]. The incretin effect is deficient in type 2 diabetes. The GLP 1 is secreted by the L cells of the intestinal mucosa after meals. Exenatide mimics GLP-1 and has the following functions. Recently FDA has issued a new warning about the possibility of acute pancreatities with Byetta-the available brand of exenatide
- It stimulates insulin secretion.
- It suppresses Glucagon secretion.
- It delays gastric emptying.
- It enhances satiety leading to weight loss.
- It enhances beta cell replication
- It is indicated in type 2 diabetic patients with uncontrolled blood sugars on 1 or more oral hypoglycemics. The side effects are related to gastrointestinal tract such as nausea and hypoglycemia.
Amylin Agonist
Amylin is a peptide secreted by the pancreatic beta cells along with insulin in response to a meal. Type 1 diabetes is an amylin deficient state. Pramlintide is a synthetic amylin analogue. It is injected 15 minutes before a meal and has the following actions
- It slows gastric emptying hence blunts post prandia hyperglycemia.
- It suppresses plasma levels of glucagon.
- It increases satiety
- The side effects are nausea and hypoglycemia.
Insulin
Insulin has short acting, intermediate acting and long acting preparations.
The short term insulins are used in combination with basal insulin such as Lantus or intermediate insulin such as NPH.
Inhaled Insulin
Last year FDA approved the first inhalable form of insulin. It’s a recombinant insulin that comes in a powdered form and used with a special inhalation delivery system that delivers about 40% of it to the lungs. It has a quick onset of action and is used three times a day. The serious side effects are hypoglycemia and loss of pulmonary function indicated by reduced FEV1 and carbon monoxide diffusion capacity. It is contraindicated in smokers, asthmatics and those with COPD and pulmonary diseases.
