Effects of Pioglitazone in Combination with Metformin or a Sulfonylurea Compared to a Fixed-Dose Combination of Metformin and Glibenclamide in Patients with Type 2 Diabetes

Emergency Department, University Hospital St. Martin, Genoa, Italy.
Diabetes Technology &amp Therapeutics (Impact Factor: 2.11). 08/2007; 9(4):387-98. DOI: 10.1089/dia.2006.0023
Source: PubMed


This study was designed to compare the effectiveness of co-administration of pioglitazone with metformin or a sulfonylurea (SU), with a fixed-dose combination of metformin and glibenclamide on glycemic control and beta-cell function in patients with type 2 diabetes.
Patients (n = 250) treated with metformin (<or=3 g/day) or an SU as monotherapy for >3 months and with glycosylated hemoglobin (HbA(1c)) between 7.5% and 11% inclusive were randomized to receive either pioglitazone (15-30 mg/day) as add-on therapy to metformin or an SU or a fixed-dose combination of metformin (400 mg) and glibenclamide (2.5 mg) (up to three tablets per day) for 6 months. HbA(1c) and fasting plasma glucose (FPG) were measured at baseline and 2, 4, and 6 months. C-peptide levels were measured at baseline and 6 months, and post-challenge glucose and insulin responses were measured.
After 6 months, pioglitazone-based and fixed-dose metformin + glibenclamide resulted in similar reductions in HbA(1c) (-1.11% vs. -1.29%, respectively; P = 0.192) and FPG (-2.13 vs. -1.81 mmol/L, respectively; P = 0.370). Patients treated with pioglitazone for 6 months had significantly reduced C-peptide levels compared with baseline (-0.09 nmol/L, P = 0.001), while patients receiving fixed-dose metformin + glibenclamide combination had slightly increased C-peptide levels (+0.04 nmol/L, P = 0.08). Pioglitazone treatment also improved post-challenge insulin responses.
Co-administration of pioglitazone with metformin or an SU is an effective alternative to fixed-dose metformin + glibenclamide combination for patients with type 2 diabetes. The complementary effects of pioglitazone with either metformin or an SU may also have the potential to preserve beta-cell function and delay the progression of type 2 diabetes.

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    • "However, few randomized studies have compared the commonly prescribed oral hypoglycemic combination of a sulfonylurea (SU) plus metformin (Met) (SU + Met) with the Pio combinations Pio + SU [10] or Pio + Met [11,12]. There has only been one randomized study directly comparing the aforementioned 3 combinations [13], and one observational study comparing Pio + Met versus SU + Met [14], and neither evaluated lipid profile. A subanalysis of the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) in patients with T2D and established CVD evaluated the lipid profile of the 3 combinations, among others, but no comparisons were performed among them; rather, Pio + SU and Pio + Met were compared with the respective SU and Met monotherapies plus placebo, and SU + Met + Pio was compared with SU + Met + placebo [15]. "
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    ABSTRACT: Type 2 diabetes (T2D) is strongly associated with cardiovascular risk and requires medications that improve glycemic control and other cardiovascular risk factors. The authors aimed to assess the relative effectiveness of pioglitazone (Pio), metformin (Met) and any sulfonylurea (SU) combinations in non-insulin-treated T2D patients who were failing previous hypoglycemic therapy. Over a 1-year period, two multicenter, open-labeled, controlled, 1-year, prospective, observational studies evaluated patients with T2D (n = 4585) from routine clinical practice in Spain and Greece with the same protocol. Patients were eligible if they had been prescribed Pio + SU, Pio + Met or SU + Met serving as a control cohort, once they had failed with previous therapy. Anthropometric measurements, lipid and glycemic profiles, blood pressure, and the proportions of patients at microvascular and macrovascular risk were assessed. All study treatment combinations rendered progressive 6-month and 12-month lipid, glycemic, and blood pressure improvements. Pio combinations, especially Pio + Met, were associated with increases in HDL-cholesterol and decreases in triglycerides and in the atherogenic index of plasma. The proportion of patients at high risk decreased after 12 months in all study cohorts. Minor weight changes (gain or loss) and no treatment-related fractures occurred during the study. The safety profile was good and proved similar among treatments, except for more hypoglycemic episodes in patients receiving SU and for the occurrence of edema in patients using Pio combinations. Serious cardiovascular events were rarely reported. In patients with T2D failing prior hypoglycemic therapies, Pio combinations with SU or Met (especially Pio + Met) improved blood lipid and glycemic profiles, decreasing the proportion of patients with a high microvascular or macrovascular risk. The combination of Pio with SU or Met may therefore be recommended for T2D second-line therapy in the routine clinical practice, particularly in patients with dyslipidemia.
    Cardiovascular Diabetology 02/2011; 10(1):18. DOI:10.1186/1475-2840-10-18 · 4.02 Impact Factor
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    • "A sulfonylurea–TZD combination offers the added benefit of lowered insulin resistance and potential improvement in β-cell function. The combination of pioglitazone or rosiglitazone with metformin or with a sulfonylurea has been shown to be an effective alternative to combined metformin and sulfonylurea.38,63,65–68 "
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    ABSTRACT: There is a need to evaluate oral glucose-lowering agents not only for their value in achieving glycemic control but also for their impact on cardiac risk factor modification. This article reviews the evidence base for the two thiazolinediones currently available, pioglitazone and rosiglitazone. These drugs exert their effects through actions affecting metabolic control, lipid profiles, and the vascular wall. They have been shown to be as efficacious in establishing glycemic control, in both monotherapy and combination therapy regimens, as more traditional oral agents, and may be able to sustain that control in the long term. Both thiazolidinediones have demonstrated favorable effects on markers of cardiovascular disease. Evidence from the large PROactive outcomes study suggests that pioglitazone may exert protective effects in patients with type 2 diabetes and macrovascular disease. Thiazolidinediones are generally well tolerated but they can cause weight gain, induce fluid retention, and may contribute to bone loss in postmenopausal women. The place of thiazolidinediones in the management of type 2 diabetes is well established. The potential for additional benefits in reducing macrovascular risk encourages further long-term study of these agents.
    Vascular Health and Risk Management 02/2009; 5(1):141-51. DOI:10.2147/VHRM.S4664
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