A closer look at new FDA actions

Takeda Pharmaceuticals'

Duetact

Takeda Pharmaceuticals North America Inc has received FDA approval for Duetact (pioglitazone HCl and glimepiride) for the treatment of type 2 diabetes in adult patients.^{1,2 The combination tablet consists of 2 hypoglycemic medications with synergistic mechanisms: the pioglitazone component works peripherally to improve insulin sensitivity, while the glimepiride component targets the pancreas to increase insulin release. Both ingredients are currently marketed individually and have established safety and efficacy in the treatment of type 2 diabetes. Duetact is promoted to simplify patients' medication regimens and will be available in 2 strengths: 30 mg/2 mg and 30 mg/4 mg.}2

Mechanism of Action

Pioglitazone hydrochloride, a thiazolidinedione medication, has been shown to inhibit hepatic gluconeogenesis and decrease insulin resistance in the muscle and adipose tissue. Pioglitazone is a very selective agonist of the peroxisome proliferator-activated receptor-gamma, which is responsible for insulin action in the adipose tissue, skeletal muscle, and liver. As a result, insulin resistance is decreased, and circulating insulin has a greater response at its receptors.

Glimepiride, a sulfonylurea agent, exerts its hypoglycemic effects by directly stimulating the release of insulin from the beta cells of the pancreas.1

Clinical Trials

No clinical trials have evaluated therapy with Duetact; however, the safety and efficacy of pioglitazone and glimepiride have been previously demonstrated. Two randomized clinical studies have evaluated pioglitazone with a sulfonylurea agent in patients with type 2 diabetes. In the first study, patients were randomized to receive placebo, 15 mg pioglitazone, or 30 mg pioglitazone daily in addition to treatment with a sulfonylurea. Both hemoglobin A1C and fasting plasma glucose were significantly lower in the pioglitazone groups.

In the second study, the treatment groups had therapy with either a sulfonylurea agent and 30 mg pioglitazone daily or a sulfonylurea agent and 45 mg pioglitazone daily. Both studies found that the addition of pioglitazone to a sulfonylurea regimen resulted in improved glucose control, regardless of the sulfonylurea dose.Safety

Duetact should not be used by any patients with a known hypersensitivity to any of its components. Patients with diabetic ketoacidosis with or without coma should not be treated with Duetact.^{1 A prospective clinical study by the University Group Diabetes Program found that patients receiving the oral hypoglycemic agent tolbutamide were at a higher risk for cardiovascular mortality, compared with patients who controlled their diabetes by diet alone. Although tolbutamide is not a component of Duetact, it is similar in class and structure to glimepiride. As a result, Takeda has included a warning for patients about the potential increased risk of cardiac mortality when using Duetact.}1Treatment with Duetact may result in edema or swelling that may cause or worsen heart failure.^{2 Patients with New York Heart Association Class III and IV cardiac status (moderate-tosevere heart failure) should not be treated with Duetact. Patients with liver disease should not use Duetact; liver function tests are recommended before initiating treatment with Duetact and periodically thereafter.}1,2 As with all sulfonylurea agents, hypoglycemia may occur.^{1 Duetact is not appropriate for patients who are pregnant or breast-feeding.}2 Duetact is not approved for use in pediatric patients. Macular edema has occurred in some patients using pioglitazone or another thiazolidinedione; patients should receive regular eye examinations while using Duetact and should report any changes in vision to a health care professional immediately.^{1 In clinical trials, the most common side effects from Duetact were upper respiratory infections, weight gain, edema, hypoglycemia, and headache.}2Patient Education

Duetact should be taken once daily with the first main meal of the day.1 Patients using Duetact may experience hypoglycemia and should be educated to recognize and respond to its signs and symptoms.References

• Duetact. Prescribing information. Available at: www.actos.com/pi_duetact.pdf. Accessed April 2007.
• Duetact. Product information. Available at: www.tpna.com/duetact.asp. Accessed April 2007.
• Duetact (pioglitazone HCl and glimepiride) Now Available in US Pharmacies. Available at: www.tpna.com/prdetail.asp?articleid=129. Accessed April 2007.