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        Repaglinide/Pioglitazone Combination Therapy Appears Safe, Effective for Patients with Type 2 Diabetes

        A DGReview of :"Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone"
        Diabetes Research and Clinical Practice

        02/03/2004
        By Keely S. Solomon, Ph.D.


        Combination therapy with repaglinide and pioglitazone is safe and effective for patients with type 2 diabetes, according to a new American study.

        Previous studies have demonstrated that combination therapy with repaglinide, a short-acting insulin secretagogue, and insulin sensitising agents such as metformin or troglitazone produces greater glycaemic effects than any of the agents as monotherapy. However, combination therapy with repaglinide and pioglitazone, a newer thiazolidinedione, has not been previously evaluated.

        These observations prompted Lois Jovanovic, MD, of Sansum Medical Research Institute, Santa Barbara, California, and colleagues to perform a randomised, controlled study examining the efficacy and safety of repaglinide/pioglitazone combination therapy in a cohort of 246 patients with type 2 diabetes.

        All participants had been unsuccessfully treated with a sulfonylurea or metformin prior to the study. After a 2-week washout period for previous diabetes medications, 61 patients were randomly assigned to treatment with either repaglinide monotherapy (mean age, 57.8; 36 males), 62 to pioglitazone monotherapy mean age, 56.2; 31 males), and 123 to combination therapy (mean age, 58.9; 84 males) for a period of 24 weeks. Pioglitazone dosage for combination or monotherapy was fixed at 30 mg per day, and repaglinide dosage was adjusted (up to maximum of 4 mg per meal) during the first 12 weeks.

        According to Dr. Jovanovic, glycosylated haemoglobin (Hb1Ac) values became significantly lower in the combination group compared with either monotherapy group beginning at week 8. Final changes in Hb1Ac values relative to baseline were -1.76% for combination therapy, -0.18% for repaglinide monotherapy and +0.32% for pioglitazone monotherapy (P < .001 for combination therapy relative to monotherapies). Mean reductions in fasting plasma glucose values were also significantly greater for the combination therapy group (-82 mg/dL) compared with either monotherapy group (repaglinide, -34 mg/dL; pioglitazone, -18 mg/dL; P < .001).

        No events of major hypoglycaemia occurred during the study, and the incidence of minor hypoglycaemic events with combination therapy (5%) was similar to monotherapy (repaglinide, 8%; pioglitazone, 3%). The researchers found weight gains to be directly correlated to reduction of HbA1c values.

        "Use of repaglinide with pioglitazone is safe, well tolerated, and efficacious in improving the glycaemic control of patients with type 2 diabetes," the researchers conclude. They recommend additional trials to determine whether the beneficial effects can be sustained over longer periods.

        Diabetes Res Clin Pract 2004 Feb;63:2:127-34. "Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone"

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