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Glycemic control in patients with type 2 diabetes mellitus switched from twice-daily immediate-release metformin to a once-daily extended-release formulation

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      Abstract

      The extended-release formulation of metformin (MXR) prolongs drug absorption in the upper gastrointestinal tract and permits once-daily dosing in patients with type 2 diabetes mellitus. This newer formulation may enhance patient compliance with oral therapy and improve long-term control of diabetes compared with the conventional immediate-release formulation of metformin (MIR).
      The goal of this study was to determine the effects on glycemic control of a switch to MXR therapy in patients with type 2 diabetes currently treated with MIR.
      This was a multicenter, randomized, double-blind, parallel-group study in patients with established type 2 diabetes. Eligible patients were to have a glycated hemoglobin (HbA1c) value ≤8.5% and mean fasting plasma glucose (FPG) concentrations ≤200 mg/dL while receiving MIR 500 mg BID for at least 8 weeks. After a 2-week, single-blind lead-in period, patients were randomly assigned to receive MXR 1000 or 1500 mg QD for 24 weeks or to continue MIR 500 mg BID for 24 weeks. The primary efficacy variable was change in HbA1c from baseline to week 12. Other variables included change in FPG levels; change in HbA1c; distribution of HbA1c values; mean daily blood glucose concentrations (self-monitored); levels of fructosamine, serum insulin, and lipids; and body weight.
      Two hundred seventeen patients were randomized to treatment. The mean change from baseline in HbA1c values at weeks 12 and 24 were small and similar in the 3 treatment groups. At week 12, the mean change from baseline in HbA1c was 0.15% for MIR, 0.23% for MXR 1000 mg, and 0.04% for MXR 1500 mg. The corresponding mean changes at week 24 were 0.06%, 0.25%, and 0.14%.
      In this study, patients with type 2 diabetes who had been receiving twice-daily MIR achieved comparable glycemic control when therapy was switched to once-daily MXR at the same or a greater total daily dose.

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      References

        • UK Prospective Diabetes Study (UKPDS) Group
        Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34).
        Lancet. 1998; 352: 854-865
      1. (Texas Diabetes Council/Texas Department of Health. Glycemic control algorithm for type 2 diabetes mellitus in adults. Available at:)
        (Accessed October 24, 2002)
        • Hawkins D.
        • Bradberry J.C.
        • Cziraky M.J.
        • et al.
        National Pharmacy Cardiovascular Council treatment guidelines for the management of type 2 diabetes mellitus: Toward better patient outcomes and new roles for pharmacists.
        Pharmacotherapy. 2002; 22: 436-444
        • Johnson A.B.
        • Webster J.M.
        • Sum C.F.
        • et al.
        The impact of metformin therapy on hepatic glucose production and skeletal muscle glycogen synthase activity in overweight type II diabetic patients.
        Metabolism. 1993; 42: 1217-1222
        • DeFronzo R.A.
        • Barzilai N.
        • Simonson D.C.
        Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects.
        J Clin Endocrinol Metab. 1991; 73: 1294-1301
        • DeFronzo R.A.
        • Goodman A.M.
        • Multicenter Metormin Study Group
        Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus.
        N Engl J Med. 1995; 333: 541-549
        • Garber A.J.
        • Duncan T.G.
        • Goodman A.M.
        • et al.
        Efficacy of metformin in type II diabetes: Results of a double-blind, placebo-controlled, dose-response trial.
        Am J Med. 1997; 103: 491-497
        • Cusi K.
        • Consoli A.
        • DeFronzo R.A.
        Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus.
        J Clin Endocrinol Metab. 1996; 81: 4059-4067
        • Inzucchi S.E.
        • Maggs D.G.
        • Spollett G.R.
        • et al.
        Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus.
        N Engl J Med. 1998; 338: 867-872
        • Prager R.
        • Schernthaner G.
        • Graf H.
        Effect of metformin on peripheral insulin sensitivity in non insulin dependent diabetes mellitus.
        Diabetes Metab. 1986; 12: 346-350
        • Vidon N.
        • Chaussade S.
        • Noel M.
        • et al.
        Metformin in the digestive tract.
        Diabetes Res Clin Pract. 1988; 4: 223-229
        • Marathe P.H.
        • Arnold M.E.
        • Meeker J.
        • et al.
        Pharmacokinetics and bioavailability of a metformin/glyburide tablet administered alone and with food.
        J Clin Pharmacol. 2000; 40: 1494-1502
        • Donahue S.
        • Marathe P.
        • Guld T.
        • Meeker J.
        The pharmacokinetics and pharmacodynamics of the metformin extended-release tablet versus immediate-release metformin in subjects with type 2 diabetes.
        Diabetes. 2002; 51 (Abstract): A468
        • Marathe P.
        • Turner K.
        Steady-state pharmacokinetics of the metformin extended-release tablet versus the immediate-release metformin tablet in healthy subjects.
        Diabetes. 2002; 51 (Abstract): A474
        • Eisen S.A.
        • Miller D.K.
        • Woodward R.S.
        • et al.
        The effect of prescribed daily dose frequency on patient medication compliance.
        Arch Intern Med. 1990; 150: 1881-1884
        • Cramer J.A.
        • Mattson R.H.
        • Prevey M.L.
        • et al.
        How often is medication taken as prescribed? A novel assessment technique.
        JAMA. 1989; 261: 3273-3277
        • Dezii C.M.
        • Kawabata H.
        • Tran M.
        Effects of once-daily and twice-daily dosing on adherence with prescribed glipizide oral therapy for type 2 diabetes.
        South Med J. 2002; 95: 68-71
        • The Diabetes Control and Complications Trial Research Group
        The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.
        N Engl J Med. 1993; 329: 977-986
        • Melikian C.
        • White T.J.
        • Vanderplas A.
        • et al.
        Adherence to oral antidiabetic therapy in a managed care organization: A comparison of monotherapy, combination therapy, and fixed-dose combination therapy.
        Clin Ther. 2002; 24: 460-467
        • Cusi K.
        • DeFronzo R.A.
        Metformin: A review of its metabolic effects.
        Diabetes Rev. 1998; 6: 89-131
        • Raz I.
        • Delaet I.
        • Goyvaerts H.
        • et al.
        Safety and efficacy of a novel extended-release formulation of metformin in patients with type 2 diabetes.
        Diabetes. 2000; 49 (Abstract): A363
        • Brazg R.
        • Decherney S.
        • Proszynski E.
        • et al.
        Safety and efficacy of a novel extended-release formulation of metformin in patients with type 2 diabetes: A dose-ranging study.
        Diabetes. 2000; 49 (Abstract): A99
      2. Glucophage® and Glucophage® XR [package inserts]. Bristol-Myers Squibb Company, Princeton, NJ2002