New combination pill approved for Type 2 diabetes

August 11, 2008

A fixed-dose combination pill from Novo Nordisk and Sciele Pharma will give patients with diabetes a new option.

A new fixed-dose combination pill from Novo Nordisk and Sciele Pharma will now offer patients with diabetes mellitus another treatment option. The Food and Drug Administration (FDA) approved PrandiMet, the first and only fixed-dose combination that comprises a fast-acting secretagogue repaglinide (Prandin) and insulin sensitizer, metformin, for patients unable to achieve glycemic control using the single therapy of meglitinide or metformin.

According to Novo Nordisk and Sciele Pharma, PrandiMet works to optimize glycemic control by counteracting the three abnormalities of Type 2 diabetes: impaired insulin secretion, insulin resistance, and excessive hepatic glucose production.

"This new combination drug brings together two anti-diabetic agents with different mechanisms of action," Sum Lam, Pharm.D., CGP, BCPS, assistant clinical professor at St. John's University, said.

PrandiMet's approval was based on a clinical trial in which 83 patients with Type 2 diabetes with inadequate glycemic control on metformin were randomized to receive add-on repaglinide, repaglinide monotherapy, or continued treatment with metformin monotherapy. Patients receiving combination therapy of metformin and repaglinide had a statistically significant improvement in HbA1c and fasting plasma glucose compared with both monotherapy arms (p<0.05).

PrandiMet is administered twice daily with meals. The starting dose should be individualized, based on the patient's current regimen, effectiveness, and tolerability. For patients who have inadequate glycemic control with metformin monotherapy, the initial recommended dose of PrandiMet is 1 mg repaglinide/500 mg metformin and titrated to reduce the risk of hypoglycemia with repaglinide. To reduce gastrointestinal side effects associated with starting metformin therapy, the recommended initial dosage for patients inadequately controlled with repaglinide therapy and starting PrandiMet is 1mg replaglinide/500 mg metformin, or 2 mg repaglinide/500 mg metformin.

PrandiMet can be given two to three times a day, but it should not exceed the maximum recommended daily dose of 10 mg repaglinide/2500 mg metformin. The total dose per meal should not exceed 4 mg repaglinide/1000 mg.

Since PrandiMet contains the component metformin, there is a potential for lactic acidosis due to metformin accumulation; this is mentioned as a black box warning. Lactic acidosis is a serious but rare complication that patients need to be aware of and the risk is intensified with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, and acute congestive heart failure. As a preventative measure against lactic acidosis, PrandiMet should be temporarily discontinued prior to radiologic studies involving intravascular iodinated contrast materials and restarted after 48 hours of stabilized renal function.

Patients' ≥ 80 years old should not be prescribed this medication unless there is a determination of normal renal function. Additionally, patients with existing renal impairment may have an increased risk of lactic acidosis; it is important to remember that metformin is contraindicated in those with serum creatinine levels of ≥ 1.5 mg/dL for males or ≥ 1.4 mg/dL for females.

Other contraindications include using this medication in patients with metabolic acidosis and diabetic ketoacidosis. PrandiMet should also be avoided in patients with hepatic impairment.

TIPS TO REMEMBER PrandiMet

THE AUTHOR is a writer based in New York.