AVANDIA - GENERIC

BACKGROUND: Thiazolidinediones are antidiabetic agents that improve insulin sensitivity (IS). Accumulating data indicate that these agents provide beneficial effects beyond glycemic control, such as improvement in vascular function. The aim of this study was to determine the effect of rosiglitazone on urine albumin excretion (UAE) in patients with type 2 diabetes mellitus (DM) and hypertension. METHODS: The study involved 20 subjects with type 2 DM who were already on 15 mg glibenclamide daily but were achieving poor glycemic control and who had either poorly controlled or newly diagnosed hypertension. In these patients, rosiglitazone (4 mg daily) was added to the existing therapeutic regimen for 26 weeks. At baseline and the end of the treatment, subjects gave a 24-h urine collection for direct measurement of albumin and a spot specimen for determination of the albumin-to-creatinine ratio (ACR). Subjects also had a hyperinsulinemic euglycemic clamp and an ambulatory blood pressure (BP) monitoring. RESULTS: At the end of the study, UAE was significantly reduced versus baseline, as measured either directly in the 24-h collection (22.4 +/- 4.6 v 13.8 +/- 3.0 mg/day, P < .05) or with ACR (20.9 +/- 3.8 v 14.0 +/- 2.8 mg/g, P < .05). The percentage changes in UAE (DeltaALB for the 24-h collection and DeltaACR for ACR) correlated with the respective changes in IS (r = -0.64, P < .01 for DeltaALB and r = -0.48, P < .05 for DeltaACR), systolic BP (r = 0.63, P < .01 and r = 0.58, P < .01 respectively), and diastolic BP (r = 0.56, P < .05 and r = 0.50, P < .05 respectively). CONCLUSIONS: In this study, treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly decreased UAE. Lowering of BP and improvement of IS should play roles in this UAE reduction.

Abstract Resistin is a protein secreted from adipose tissue that is thought to play a role in insulin sensitivity. We examined the effects of rosiglitazone and metformin on the plasma resistin levels in individuals with type 2 diabetes mellitus. Patients with type 2 diabetes mellitus who showed poor glycemic control with glimepiride (4 mg/d) were randomized to rosiglitazone (4 mg/d) and metformin (500 mg bid) treatment groups. All subjects continued glimepiride treatment as well. The plasma concentrations of resistin were measured at baseline and at 6 months of treatment for both groups. The anthropometric parameters, fasting plasma glucose, HbA1c, total cholesterol, triglyceride, high-density lipoprotein cholesterol, free fatty acids, and adiponectin concentrations were also measured. After 6 months of treatment, the reduction in plasma glucose levels was similar between the 2 groups. There were no significant changes in the lipid profiles of either group during the study period. The plasma resistin levels decreased in the rosiglitazone group (2.49 +/- 1.93 vs 1.95 +/- 1.59 ng/ml; P < .05) but increased in the metformin group (2.61 +/- 1.69 vs 5.13 +/- 2.81 ng/ml; P < .05). The plasma adiponectin concentrations were increased in the rosiglitazone group (2.91 +/- 1.46 vs 4.23 +/- 1.77 mu g/ml; P < .05) but were unchanged in the metformin group. In summary, rosiglitazone treatment decreased the plasma resistin levels whereas metformin treatment increased them in patients with type 2 diabetes mellitus showing poor glycemic control with sulfonylurea therapy. These results suggest that the observed changes in plasma resistin levels are not the consequences of improved insulin resistance, nor are they consequences of glycemic control. Considering the potential role of resistin in insulin resistance, decrease in resistin levels may contribute to improving insulin action with rosiglitazone treatment.

GENERIC NAME: rosiglitazone maleate
BRAND NAME: Avandia

DRUG CLASS AND MECHANISM: Rosiglitazone is a drug that reduces the amount of glucose (sugar) in the blood. It is in a class of anti-diabetic drugs called "thiazolidinediones" that are used in the treatment of type II diabetes. The other member in this class is pioglitazone (Actos). (Another member of this class, troglitazone or Rezulin, was removed from the market because of liver toxicity.) Patients with type II diabetes cannot make enough insulin, and the cells of their body do not respond normally to the reduced amounts of insulin that are present. (Insulin is the hormone produced by the pancreas that stimulates cells to remove glucose from the blood.) Rosiglitazone often is referred to as an "insulin sensitizer" because it attaches to the insulin receptors on cells throughout the body and causes the cells to become more sensitive (more responsive) to insulin. As a result, more glucose is removed from the blood. At least some insulin must be produced by the pancreas in order for rosiglitazone to function. Rosiglitazone was approved by the FDA on May 28, 1999.

PREPARATIONS: Film-coated tablets: 2, 4, and 8 mg.

STORAGE: Film-coated tablets should be kept at room temperature, 15-30°C (59-86°F).

PRESCRIBED FOR: Rosiglitazone is used for the treatment of type II diabetes along with a healthy diabetic diet, regular exercise, weight control, smoking reduction, and careful monitoring of blood glucose. Rosiglitazone may be used alone or in combination with metformin, another type of anti-diabetic drug that also lowers blood glucose, sulfonylureas, another class of anti-diabetic drug, or insulin in type II diabetes. Since it requires naturally-secreted insulin to be effective, rosiglitazone is not recommended in type I diabetes where the amount of insulin is very low or absent.

DOSING: Rosiglitazone may be taken once or twice daily, with or without meals. Daily doses range from 4 to 8 mg either with or without metformin. Studies do not demonstrate additional effects when more than 8mg per day are taken.

DRUG INTERACTIONS: Drug interactions seen with the other two anti-diabetic thiazolidinedione drugs have not been seen with rosiglitazone because it has a different method of elimination from the body. Studies using rosiglitazone, 4-8 mg per day, did not cause changes in blood levels of the commonly-used drugs, digoxin and warfarin. Alcohol did not interact with rosiglitazone (reduce the level of blood sugar further) when the alcohol consumption was limited to a single episode of moderate consumption.

PREGNANCY: There are no adequate studies of rosiglitazone in pregnant women. Rosiglitazone may be used in pregnancy if the physician judges the potential risks to be outweighed by the benefits.

NURSING MOTHERS: It is unknown if rosiglitazone is secreted in breast milk. Therefore, the safety of rosiglitazone to nursing infants also is unknown.

SIDE EFFECTS AND PRECAUTIONS: The most common side effects seen with rosiglitazone alone or in combination with metformin are upper respiratory tract infection, headache, back pain, hyperglycemia, fatigue, sinusitis, diarrhea, and hypoglycemia. Rosiglitazone has been shown to cause mild to moderate accumulation of fluid (edema) and can lead to heart failure. In addition, anemia occurs with rosiglitazone alone or combined with metformin but also does not require discontinuation of either drug.

Since troglitazone, a related drug, was associated with liver injury, it is recommended that periodic monitoring of liver tests be done in patients taking rosiglitazone. Side effects of rosiglitazone which may suggest liver injury include unexplained nausea, vomiting, abdominal pain, fatigue, anorexia (loss of appetite), or dark urine.

Rosiglitazone may cause ovulation in women who have stopped ovulating and who are considered premenopausal and are resistant to insulin. Rosiglitazone may improve insulin sensitivity sufficiently and lead to ovulation. Therefore, there is the potential for pregnancy to occur.

Studies testing rosiglitazone excluded New York Heart Association Class III and IV patients who have more serious heart disease. Therefore, it is not known how these classes of patients will respond to treatment. The concern is that fluid accumulation may be more likely to lead to heart failure in these patients.

Rosiglitazone alone or combined with metformin have demonstrated various effects on blood lipids . Studies have shown elevated total and low-density cholesterol (LDL) levels within the first two months of rosiglitazone therapy with or without metformin, while high-density cholesterol (HDL) levels increase and free fatty acids decrease with continued therapy.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.