Long Term Safety of Glyburide for Diabetes Mellitus

Pioglitazone is an oral antidiabetic agent of the thiazolidinedione class indicated for use in patients with type 2 diabetes mellitus as an adjunct to diet and exercise or in combination with a sulfonylurea, metformin, or insulin when diet and exercise alone do not result in adequate glycemic control. Thiazolidinediones act on peroxisome proliferator-activated receptors (PPARs), which regulate glucose, lipid, and protein metabolism and influence cell proliferation, differentiation, and apoptosis. Through selective agonism of PPAR-g receptors, thiazolidinediones inhibit hepatic glucogenesis and increase insulin sensitivity in muscle and adipose tissue, lowering glucose levels.3 Because thiazolidinediones do not stimulate insulin secretion but enhance the effects of circulating insulin, the antihyperglycemic effect can be achieved only in the presence of insulin.

In addition to glycemic control, selected thiazolidinediones have been shown to have a beneficial effect on lipid profiles. In support of these findings, several randomized controlled trials have demonstrated improved glycemic control and favorable lipid-altering effects with once-daily pioglitazone or with a combination of pioglitazone plus metformin, a sulfonylurea, repaglinide, or insulin.[4-9] In addition, a recent head-to-head comparison trial of the thiazolidinediones pioglitazone and rosiglitazone demonstrated comparable effects on glycemic control, although pioglitazone significantly lowered triglyceride levels, increased high-density lipoprotein cholesterol levels, and decreased the number of small, dense low-density lipoprotein cholesterol particles compared with rosiglitazone.

Although thiazolidinediones have been associated with weight gain, edema, and slight reductions in hemoglobin and hematocrit levels (as a result of plasma volume expansion), several reports indicate that these adverse events are generally mild to moderate and infrequently lead to discontinuation of pioglitazone or rosiglitazone. Neither pioglitazone nor rosiglitazone has been associated with hepatotoxicity, which is linked to the thiazolidinedione troglitazone.

Oral drugs of the sulfonylurea class, such as glyburide, stimulate insulin secretion by binding to and blocking adenosine 5¢-triphosphate- dependent potassium channels in β-cell membranes. This action increases intracellular calcium concentrations, inducing insulin secretion. Because the therapeutic effect of sulfonylureas depends on their insulin secretory action, development of hypoglycemia is associated with their use.

Type 2 diabetes mellitus is a lifelong disorder requiring long-term treatment. Because, to our knowledge, no long-term safety and efficacy data comparing glyburide with pioglitazone have been collected yet, this study was conducted to determine whether long-term treatment with glyburide versus pioglitazone is safe and effective in achieving and maintaining glycemic control in patients with recently diagnosed type 2 diabetes mellitus inadequately controlled with diet and exercise.

Stop taking glyburide and seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives).

Other, less serious side effects from glyburide result mostly from blood sugar levels that are either too high or too low. You should be familiar with the symptoms of both high and low blood sugar levels and know how to treat both conditions. Also, be sure your family and close friends know how to help you in an emergency situation.

Low blood sugar may occur when too much glyburide is taken; when meals are missed or delayed; if you exercise more than usual; during illness, especially with vomiting or diarrhea; if you take other medications; after drinking alcohol; and in other situations.

Hypoglycemia or Low blood sugar has the following symptoms:

* shaking;
* headache;
* cold sweats;
* pale, cool skin;
* anxiety; and
* difficulty concentrating.

Keep hard, sugary candy; chocolate; fruit juice; or glucose tablets on hand to treat episodes of low blood sugar.

Increased blood sugar may occur when not enough glyburide is taken; if you eat significantly more food than usual; if you exercise less than usual; if you take other medications; during fever or other illness; and in other situations.

Hyperglycemia or High blood sugar has the following symptoms:

* increased thirst,
* increased hunger, and
* increased urination.

There may be an increased risk of death due to cardiovascular (heart and blood vessels) complications with the use of glyburide when compared to the treatment of diabetes with diet or diet plus insulin. The long-term use of glyburide should be discussed with your doctor.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.