We are sharing with you a summary of an excellent article from The Medical Letter, Vol.1 issue 1 Sept 2002, which outlines all of these medications. One of the interesting aspects of this excellent review is a comparison of the costs of each medication that is based on retail cost for 30 days’ treatment with the lowest daily dosage. We hope you can use it to discuss you care with your physician and health care team.
First, we will examine the medications used to treat type 2 diabetes. Then we will look at the types of insulin used in both type 1 and type 2 diabetes. Currently it is thought that type 2 diabetes is a result of a combination of metabolic abnormalities including insulin resistance, excess hepatic glucose production, and diminished insulin secretion.
Basically, most medication available today falls into 2 categories: those that increase insulin supply (we called these the pancreas jump starters in our articles). These are sulfonylureas, other secretagogues, and insulin. The second group takes on the job of decreasing insulin resistance or improves its effectiveness. They are called biguanides, and thiazolidinediones. Alpha-glucosidase inhibitors reduce the rate of glucose inhibitors reduce the rate of glucose absorption.
Oral Medications
Sulfonylureas:
There are two generations of these medications. The first generation, the oldest have names like Diabinese and Tolinase, and cost between $26 and $27 per month.
Second generation drugs, which are used more often because they are more potent, are as efficacious, and differ in dosage and duration of action, include medications such as Amaryl, Glucotrol and Glucotrol XR, as well as DiaBeta, Microase, Glynase and Prestab. Most of these can be purchased in a generic pill that is usually half the price of the non-generic, which is in the $22 to $24 range.
Failure rates with this class of medication are about 5-10% per year; when they fail, another should be tried. These medications interact with ATP-sensitive potassium channels in the beta cell membrane to increase secretion of insulin. The adverse reactions to these medications include weight gain and hypoglycemia, the later particularly in the elderly.
Non-Sulfonylurea Secretagogues:
These include name brands of Starlix and Prandin. They do not have generic brands available and cost from $77 to $84.00 per month.
These drugs bind to the same ATP-sensitive potassium channels as the Sulfonylureas to increase insulin release. Starlix appears to be more effective than Prandin in lowering HbA1c levels. Both are rapidly absorbed, resulting in peaking within 30 to 60 minutes and return to baseline before the next meal.
For that reason it must be taken before each meal. If you don’t eat, don’t take the pill. They are used in people with renal impairment and in people who don’t eat a lot. Hypoglycemia is an adverse reaction although it may be at a lower rate than with sulfonylureas.
Biguanides:
Glucophage, Glucophage XR and Glucovance are the brand names of this category, with the first two available in generic form. They range in price for generic at $51 and $52 to $69 for the name brands.
The drug works to decrease hepatic glucose output and to a lesser extent, increases peripheral glucose utilization. The XR is taken only once a day and all are about as effective as sulfonylurea in lowering HbA1c.
Alone these medications do not cause hypoglycemia nor does it cause weight gain. It may even cause weight loss perhaps because of gastrointestinal effects. Lactic acidosis is rare, but potentially a fatal complication. It can be avoided by observing the contraindications to the use of this medication, which include impaired renal function and other diseases that predispose to acidosis such as congestive heart failure, liver failure or major surgery.
The medication should not be taken when you are injected with iodinated contrast for radiographic studies. It should be started again in 48 hours after the study, after evaluating renal function. This class of medication decreases serum concentration of triglycerides and total LDL cholesterol. It may also increase fibrinolysis or lead to a resumption of menses in women with polycystic disease.
In a study of 3234 patients with impaired glucose tolerance, the medication decreased the incidence of diabetes by 31% compared to a 58% decrease with a regime of exercise and weight loss.
Thiazolidinediones:
Actos and Avandia are the only two brand names of this class of medication available in the US and no generics are available. The cost is from $76 to $88 per month.
They work by decreasing insulin resistance and increase the insulin sensitivity in adipose tissue, skeletal muscle, and the liver. Both take from 6 to 14 weeks to achieve their maximum effect. They are approved to use alone or combined with sulfonylurea or metformin.
The first thiazolidinedione, Troglitazone was removed from the market because of fatal hepatic toxicity. Clinical trials of these two medications did not detect this problem, but the FDA recommends monitoring liver function every 2 months for the first year and less frequently thereafter.
Other side effects include weight gain and fluid retention, which can lead to congestive heart failure. If you have been diagnosed with heart disease, discuss the safety of using either product with your cardiologist. Neither is recommended for use during pregnancy, as they retarded fetal growth in animal studies.
Alpha-glucosidase inhibitors:
Again, there are no generic medications in this class. The brand names are Acarbose and Miglitol which cost from $53 to $57 per month.
These medications inhibit the alph-glucosidase enzymes that line the brush border of the small intestines, interfering with hydrolysis of carbohydrates and delaying absorption of glucose and other monosaccharide. They must be taken with a meal.
One study found that prophylactic use of Acarbose effective in delaying the development of type 2 diabetes in people with impaired glucose tolerance. The adverse reactions include abdominal pain and flatulence due to the results of unabsorbed carbohydrates. For this reason, the medication may be stopped by patients. It should be started with low doses to minimize these effects.
Fatal hepatic failure after taking acarbose has been reported in Japan. Alone these drugs do not cause hypoglycemia, but taken with a sulfonylurea or insulin may increase the risk for this complication. Glucose, not sucrose, must be given if hypoglycemia occurs. This class of medication is contraindicated in people with chronic intestinal diseases, inflammatory bowel disease, colonic ulceration, or degrees of intestinal obstruction.
The drug for drug therapy of type 2 diabetes is generally an HbA1c of less than 7%. Used alone, oral hypoglycemic drugs generally lower HbA1c by less than 2%. A sulfonylurea or metformin is a reasonable first choice, but most people will need a second medication.
In general, oral agents achieve 70-80% of their maximum recommended dose. Adding a second drug, therefore, may be preferable to increasing dosage in people with persistent hyperglycemia.
Even with drug treatment, type 2 diabetes is a progressive disease with increasing hyperglycemia. After 3 years, 50% of people need a second medication; after 9 years this rate is 75%. When adding a second drug, one with a different mechanism of action is usually chosen. The most common combination is a sulfonylurea with metformin.
Recently a combination of glyburide and metformin that is known as Glucovance has come on the market. As the disease progresses a third medication may need to be added or insulin will be prescribed. Most experts suggest that the addition of insulin not be postponed when poor glycemic control is evident in spite of multiple oral medications.
Insulin
Short and rapid- acting insulins
There are two rapid-acting insulin analogs on the market. Both have rapid onset and shorter duration of action than regular insulin. These are Humalog (insulin lispro) and Novolog (insulin aspart. Depending on whether you purchase them in a vial cartridge, you will pay about $46 or $78.
They are more effective than regular insulin in controlling postprandial blood sugar. In caparison studies, there seems to be no difference in glucose control. Regular insulin costs from $25 for a vial to $70 for a 3-ml cartridge. As with all insulins, the greatest risk factor for these types of insulin is hypoglycemia. The rapid-acting insulins should be injected just before eating.
Long-acting insulins
Intermediate insulins such as NPH or lente, and long-acting insulins like ultralente (Humalin U) and insulin glargine (Lantus) are used in combination with short and rapid-acting insulins. They range in price from $23 for Humalin to $43 for Lantus.
All are effective as basic insulins given twice a day. They come already combined such as Humalin and Novolin 70/30, Humalog Mix 75/25, and Novolog Mix 70/30.
Insulin glargine forms microprecipitates in subcutaneous tissue, delaying its absorption, and prolonging its duration of action. Unlike NPH and ultralente insulin, it has no peak concentration, so it mimics a continuous infusion of rapid-acting regular insulin from a subcutaneous pump.
In people who use glargine as an basal insulin, there is a lower incidence of hypoglycemia, lower fasting blood sugars and less weight gain than with NPH. All insulins can cause hypoglycemia. Glargine may cause mild pain at the injection site. The long term use of NPH, lente and ultralente has been well established.
There is not information on whether glargine leads to long term complications of diabetes such as retinopathy or tumors associated with insulin-like growth factors.
Have any questions? After reading this review, you should find it easier to speak to your health care team or physician about your medications and how they work. You will be able to discuss various medications and insulins and not feel that you need definitions just to begin the conversation. Good luck.
