Efficacy and Safety of Pioglitazone Versus Metformin in Patients with Type 2 Diabetes Mellitus: A Double-Blind, Randomized Trial

Università degli Studi di Perugia, Perugia, Umbria, Italy
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 02/2005; 89(12):6068-76. DOI: 10.1210/jc.2003-030861
Source: PubMed


Pioglitazone increases the insulin sensitivity of peripheral tissues and may provide an alternative first-line treatment for type 2 diabetes. This study compared metabolic control in drug-naive type 2 diabetes patients given either pioglitazone or metformin. Eleven hundred and ninety-nine patients with poorly controlled type 2 diabetes mellitus [glycosylated hemoglobin (HbA1c), 7.5-11%; normal, 4.3-6.1%] were randomized to receive either pioglitazone (< or =45 mg/d) or metformin (< or =850 mg, three times daily). HbA1c, fasting plasma glucose (FPG), insulin levels, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, triglycerides, free fatty acids, and urinary albumin/creatinine ratio were measured. Mean HbA1c decreased in both treatment groups from baseline to wk 52 (-1.4% and -1.5%). Significantly greater mean reductions in FPG were observed in the pioglitazone group (-45.0 mg/dl; -2.5 mmol/liter) than in the metformin (-39.6 mg/dl; -2.2 mmol/liter) group (P = 0.016). Favorable changes in triglycerides and HDL-C were more pronounced with pioglitazone. Although low density lipoprotein cholesterol and TC levels increased with pioglitazone, TC/HDL-C ratios decreased similarly with both treatments. The urinary albumin/creatinine ratio was reduced by 19% with pioglitazone treatment, but remained unchanged with metformin therapy (-1%; P = 0.002). There was an increase in body weight of 1.9 kg in the pioglitazone group and a decrease of 2.5 kg in the metformin group. The overall frequency of adverse events was similar between treatment groups, but adverse event profiles were different between treatment groups. HbA1c reduction is similar after pioglitazone and metformin monotherapies, but differences in FPG, plasma lipids, and adverse effects between the two compounds may influence decision-making in individual prescribers.

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    • "Interestingly, the current study showed a 4.1 mmHg increase in systolic blood pressure with TZD therapy in the thirdline setting, a significant increase versus add-on glimepiride. However, previous studies have shown reduced systolic blood pressure with pioglitazone [31] [32]. In the PROactive study, systolic blood pressure was significantly lowered by 3 mmHg in the 2605 patients exposed to pioglitazone [33]. "
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    ABSTRACT: AimsThe EUREXA trial extension evaluated third-line thiazolidinedione or glimepiride therapy in patients inadequately controlled on metformin + exenatide twice daily (BID), and third-line exenatide BID in patients inadequately controlled on metformin + glimepiride.Materials and methodsIn this randomized, open-label, multicenter trial, 144 patients with type 2 diabetes inadequately controlled (glycated hemoglobin [HbA1c] >9% [75 mmol/mol] after 3 months’ treatment or >7% [53 mmol/mol] at 2 consecutive visits 3 months apart after 6 months’ treatment) on metformin + exenatide BID were re-randomized to add-on thiazolidinedione or glimepiride, and 166 patients inadequately controlled on metformin + glimepiride received add-on exenatide BID. Changes in HbA1c, body mass index (BMI), lipids, hypoglycemia, and vital signs were evaluated.ResultsMedian triple therapy duration was ~2 years. In patients inadequately controlled on metformin + exenatide BID, add-on thiazolidinedione decreased HbA1c significantly better than add-on glimepiride (130-week difference 0.48%, 95% CI 0.19–0.77 [5.2 mmol/mol, 2.1–8.4], p = 0.001), but with significantly increased BMI and systolic blood pressure. Ratio of documented symptomatic (blood glucose ≤70 mg/dl) hypoglycemia rates for add-on glimepiride to add-on thiazolidinedione was 8.48 (p < 0.0001). Add-on exenatide BID after metformin + glimepiride significantly reduced HbA1c (mean [SD] change from baseline −0.35 [0.89]% [−3.8 (9.7) mmol/mol]) and BMI (−0.82 [1.9] kg/m2) at 130 weeks, with a slightly increased rate of documented symptomatic hypoglycemia from metformin + glimepiride (ratio 1.49).Conclusions Thiazolidinedione, but not glimepiride, was an effective and well tolerated third-line therapy in patients without glycemic control after long-term therapy with metformin + exenatide BID. Exenatide BID was an effective and well tolerated third-line therapy in patients inadequately controlled on metformin + glimepiride.(NCT00359762)
    Full-text · Article · Apr 2015 · Diabetes Obesity and Metabolism
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    • "In a similar way, PPAR-␥ agonists have shown their value in the aging kidney (Table 2). In terms of surrogate endpoints, thiazolidinediones significantly reduce urinary albumin and protein excretion in patients with diabetes, when used in addition to RAS blockade (Lebovitz et al., 2001; Schernthaner et al., 2004; Matthews et al., 2005; DREAM Trial Investigators et al., 2008; Sarafidis et al., 2010; Morikawa et al., 2011; Pistrosch et al., 2012). Thiazolidinediones may well prove to have an important role in the treatment of chronic renal disease particularly in obese and insulin-resistant patients. "
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    Full-text · Article · Mar 2014 · Ageing Research Reviews
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    • "The UK National Institute for Health and Clinical Excellence (NICE) recommended metformin if the patients are at danger under hypoglycaemia [1]. The latest recommendations of ADA [2] and NICE [1] were updated with the results of UKPDS [6,7], post-trial monitoring of UKPDS [8], and systematic reviews of comparing metformin with placebo, sulfonylureas and other anti-diabetic drugs [7,9], as well as the randomized controlled trials (RCTs) comparing metformin monotherapy with pioglitazone [10], metformin plus nateglinide [11], metformin plus rosiglitazone [12] and other non-metformin treatments [13]. A meta-analysis of RCTs on the efficacy of metformin in treating T2DM [14] found metformin lacking clear evidence for efficacy over the conventional or placebo treatment. "
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    ABSTRACT: Metformin treatment has been the most recommended monotherapy of type 2 diabetes mellitus (T2DM) for decades but is challenged by new antidiabetic drugs. This study conducted a meta-analysis of randomized controlled trials (RCT) comparing the efficacy of metformin and glimepiride in monotherapy of T2DM. A literature search for RCTs on glimepiride and metformin was conducted on the bibliographic databases, including PubMed, Cochrane Library and ScienceDirect, from their inceptions to 25 Mar 2013. All RCTs were selected according to pre-specified eligibility criteria. The quality of articles was assessed with the Cochrane's risk of bias tool. Statistical meta-analysis evaluated the overall effects and biochemical indices of T2DM. Sensitivity and subgroup analyses evaluated the robustness and explained the heterogeneity of the results. Begg and Egger's tests quantified possible publication biases. Results were represented as "standard mean difference or odds ratio [95% confidence internals] P value". Fifteen RCTs with 1681 adult T2DM patients were included for meta-analysis. Metformin was not better than glimepiride in overall efficacy in controlling the levels of HbA1c, postprandial blood sugar (PPBS), fasting plasma insulin (FINS), systolic and diastolic blood pressures (SBP and DBP), and high density lipoprotein (HDL). Metformin was only more effective than glimepiride in controlling the levels of total cholesterol (TC, 0.33 [0.03, 0.63], P = 0.03), low-density lipoprotein (LDL, 0.35 [0.16, 0.53], P = 0.0002) and triglycerides (TG, 0.26 [0.05, 0.46], P = 0.01). Odds ratios of adverse events showed that glimepiride was more likely to induce hypoglycemia episodes and metformin was with a higher risk of gastrointestinal upset. Metformin was not significantly better than glimepiride in glycemic control of T2DM, suggesting that glimepiride would be a good choice second to metformin in the monotherapy of T2DM.
    Full-text · Article · Nov 2013 · Diabetology and Metabolic Syndrome
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