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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pioglitazone is a novel oral anti-diabetic agent belonging to the thiazolidinedione class. Pioglitazone has been shown to be effective and well tolerated in the treatment of patients with type 2 diabetes, as it reduces insulin resistance and improves glycaemic control and abnormal lipid profiles. This double-blind, randomised, placebo-controlled study was conducted for further evaluation of the efficacy and tolerability of once-daily administration of pioglitazone monotherapy alongside dietary measures in patients with type 2 diabetes. Following a 10-week washout period, 251 patients received one of three treatment regimens for 26 weeks: placebo + diet (n = 84), pioglitazone 15 mg once-daily + diet (n = 89), or pioglitazone 30 mg once-daily + diet (n = 78). Pioglitazone, both 15 and 30 mg/day, in addition to dietary control, was associated with significant reductions (vs. placebo) in mean levels of both glycosylated haemoglobin (HbA 1C ) and fasting blood glucose (FBG). HbA 1C was reduced by 0.92 % and 1.05 %, respectively, and FBG was reduced by 34.3 and 36.0 mg/dl, respectively, compared with the control group. Pioglitazone at 15 and 30 mg/day significantly reduced postprandial blood glucose levels at all visits (- 163 and - 165 mg/dl/hour, respectively) compared with an increase of 47.7 mg/dl/hour on placebo. The profile and frequency of adverse events were similar in all treatment groups. These results indicate that pioglitazone monotherapy together with dietary control is both effective and safe in patients with type 2 diabetes.
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PMID:Metabolic efficacy and safety of once-daily pioglitazone monotherapy in patients with type 2 diabetes: a double-blind, placebo-controlled study. 1243 88

Hypertension is often associated with insulin resistance, dyslipidemia and obesity, which indicate a prediabetic state and increased risk of cardiovascular disease. Pioglitazone treatment of patients with type 2 diabetes reduces insulin resistance and improves lipid profiles. The present double-blind placebo-controlled study is the first study to report effects of pioglitazone in non-diabetic patients with arterial hypertension. Following a one week run-in, 60 patients were randomized to receive either pioglitazone (45 mg/day) or placebo for 16 weeks. Insulin sensitivity (M-value) increased by 1.2 +/- 1.7 mg/min/kg with pioglitazone compared with 0.4 +/- 1.4 mg/min/kg (P = 0.022) with placebo. HOMA index was decreased (-22.5 +/- 45.8) by pioglitazone but not by placebo (+0.8 +/- 26.5; P < 0.001). Decreases in fasting insulin and glucose were significantly (P = 0.002 and P = 0.004, respectively) greater with pioglitazone than placebo. Body weight did not change significantly with either treatment. HDL-cholesterol was increased and apolipoprotein B was decreased to a significantly greater extent with pioglitazone. There was a significantly (P = 0.016) greater decrease from baseline in diastolic blood pressure with pioglitazone. These changes would suggest improved glucose metabolism and a possible reduction in risk of cardiovascular disease with pioglitazone treatment of non-diabetic patients with arterial hypertension.
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PMID:Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. 1246 45

(1) Treatment of type 2 (non insulin-dependent) diabetes is based on lifestyle measures and management of cardiovascular risk. (2) The reference first-line drug therapy for type 2 diabetes, when drug therapy is needed, is single-agent treatment with metformin (a biguanide) for overweight patients, or with glibenclamide (a glucose-lowering sulphonylurea) for other patients. (3) If monotherapy fails to control blood glucose levels adequately, most clinical guidelines then recommend a combination of metformin with a glucose-lowering sulphonylurea, although the few available comparative clinical data raise the possibility of excess mortality with this treatment. (4) Rosiglitazone and pioglitazone (glitazones that reduce insulin resistance) have been authorized in the European Union for combination with a glucose-lowering sulphonylurea (for patients in whom metformin is ineffective or poorly tolerated) or with metformin (for obese patients). (5) None of the available trials of rosiglitazone and pioglitazone include data on mortality or morbidity. (6) There are fewer data on pioglitazone than on rosiglitazone. (7) According to short-term comparative trials, rosiglitazone and pioglitazone are more effective than placebo on blood glucose levels. Combinations of rosiglitazone or pioglitazone with metformin or with glucose-lowering sulphonylureas have not been compared with the metformin + glucose-lowering sulphonylurea combination or with insulin. (8) Rosiglitazone and pioglitazone frequently cause weight gain. (9) Pioglitazone has a slightly favourable effect on lipid profiles, unlike rosiglitazone, which increases LDL-cholesterol levels. (10) The main side effect of rosiglitazone and pioglitazone is sodium and water retention, which can provoke oedema, anaemia (by haemodilution), and even heart failure. Rosiglitazone and pioglitazone are also hepatotoxic. (11) Combining rosiglitazone with insulin is contraindicated, owing to the increased risk of heart failure. The same applies to pioglitazone. (12) In practice, neither rosiglitazone nor pioglitazone has a place in the management of type 2 diabetes, except in the context of strictly controlled long-term comparative clinical trials.
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PMID:Rosiglitazone and pioglitazone: new preparations. Two new oral antidiabetics both poorly assessed. 1246 95

Pioglitazone is the second thiazolidine derivative used clinically in the type 2 diabetes mellitus (DM). In the prediabetic stage, hyperinsulinemia or insulin resistance has been suggested to be closely associated with the oxidative stress. The first thiazolidine derivative used to treat DM, troglitazone, is chemically related to alpha-tocopherol, a known antioxidant. Troglitazone prevents tissue damage, but has been reported to produce hepatotoxicity. Pioglitazone strongly increases insulin sensitivity, improves glucose and lipid metabolism and showed no evidence of hepatotoxicity. The mechanism of the antidiabetic action of pioglitazone involves activation of insulin receptors and/or high affinity for peroxisome proliferator-activated receptor gamma (PPARgamma). Hydroxylation of the phenyl and pyridine rings in the chemical structure of pioglitazone may facilitate the scavenging of hydroxyl radicals. The direct antioxidant effect of pioglitazone may contribute to its effect on insulin resistance. The hypoglycemic and hypolipidemic effects of pioglitazone are likely to reduce the expression of TNFalpha. The reduction in the oxidative stress may lead to the suppression of TGFbeta and of collagen accumulation. A decrease in collagen content is likely to improve left ventricular diastolic function and distensibility of the aortic wall. Reduction in the oxidative stress may prevent the proliferation of vascular smooth muscle cells and contribute to the decrease in the aortic wall stiffness.
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PMID:Pioglitazone: cardiovascular effects in prediabetic patients. 1248 Dec 3

We tested the hypothesis that pioglitazone (insulin sensitizer) reduces oxidative stress and improves aortic wall distensibility in the pre-diabetic stage of Otsuka Long-Evans Tokushima Fatty rats, type 2 diabetes mellitus (DM) model. 20 DM and 9 nonDM male rats were divided into 3 groups: treated-DM, untreated-DM, and untreated-nonDM. Pioglitazone (0.01%) was mixed in chow in the treated group from 15 to 20 weeks of age. At baseline and 20 weeks, plasma malondialdehyde (MDA) was measured. At 20 weeks, intravascular ultrasound images and aortic pressure were simultaneously recorded. Stiffness parameter beta was calculated from the cyclic variations of aortic diameter and pressure. From an excised thoracic aorta, aortic wall collagen was measured, and the morphology was histopathologically evaluated by hematoxylin-eosin staining. At 20 weeks, MDA (nmol/ml) in treated-DM (2.3 +/- 0.3) was lower than in untreated-DM (3.2 +/- 0.6, p < 0.0001). beta in treated-DM (0.53 +/- 0.21) was smaller than that in untreated-DM (0.88 +/- 0.26, p = 0.0067). Aortic wall collagen (mg/100 mg dry weight) did not decrease in treated-DM (22.3 +/- 3.2 vs untreated-DM : 19.6 +/- 4.7). Lumen/medial area ratio (L/M) increased in treated-DM (2.79 +/- 0.40 vs untreated-DM : 2.22 +/- 0.20, p = 0.0041, untreated-nonDM : 2.25 +/- 0.55, p = 0.0075). MDA was significantly correlated with beta (r = 0.65, p = 0.0005) or L/M (r = -0.60, p = 0.0008). Pioglitazone may reduce oxidative stress and contribute to improvement of aortic wall stiffness without decrease in collagen content at an early prediabetic stage of type 2 DM.
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PMID:Improvement of aortic wall distensibility and reduction of oxidative stress by pioglitazone in pre-diabetic stage of Otsuka Long-Evans Tokushima fatty rats. 1265 12

Pioglitazone, a thiazolidinedione, improves glycemic control primarily by increasing peripheral insulin sensitivity in patients with type 2 diabetes, whereas metformin, a biguanide, exerts its effect primarily by decreasing hepatic glucose output. In the first head-to-head, double-blind clinical trial comparing these two oral antihyperglycemic medications (OAMs), we studied the effect of 32-wk monotherapy on glycemic control and insulin sensitivity in 205 patients with recently diagnosed type 2 diabetes who were naive to OAM therapy. Subjects were randomized to either 30 mg pioglitazone or 850 mg metformin daily with titrations upward to 45 mg (77% of pioglitazone patients) and 2550 mg (73% of metformin patients), as indicated, to achieve fasting plasma glucose levels of less than 7.0 mmol/liter (126 mg/dl). Pioglitazone was comparable to metformin in improving glycemic control as measured by hemoglobin A1C and fasting plasma glucose. At endpoint, pioglitazone was significantly more effective than metformin in improving indicators of insulin sensitivity, as determined by reduction of fasting serum insulin (P = 0.003) and by analysis of homeostasis model assessment for insulin sensitivity (HOMA-S; P = 0.002). Both OAM therapies were well tolerated. Therefore, pioglitazone and metformin are equally efficacious in regard to glycemic control, but they exert significantly different effects on insulin sensitivity due to differing mechanisms of action. The more pronounced improvement in indicators of insulin sensitivity by pioglitazone, as compared with metformin monotherapy in patients recently diagnosed with type 2 diabetes who are OAM-naive, may be of interest for further clinical evaluation.
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PMID:Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes. 1267 50

The effect of pioglitazone on splanchnic glucose uptake (SGU), endogenous glucose production (EGP), and hepatic fat content was studied in 14 type 2 diabetic patients (age 50 +/- 2 years, BMI 29.4 +/- 1.1 kg/m(2), HbA(1c) 7.8 +/- 0.4%). Hepatic fat content (magnetic resonance spectroscopy) and SGU (oral glucose load- insulin clamp technique) were quantitated before and after pioglitazone (45 mg/day) therapy for 16 weeks. Subjects received a 7-h euglycemic insulin (100 mU. m(-2). min(-1)) clamp, and a 75-g oral glucose load was ingested 3 h after starting the insulin clamp. Following glucose ingestion, the steady-state glucose infusion rate during the insulin clamp was decreased appropriately to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in glucose infusion rate during the 4 h after glucose ingestion from the ingested glucose load. 3-[(3)H]glucose was infused during the initial 3 h of the insulin clamp to determine rates of EGP and glucose disappearance (R(d)). Pioglitazone reduced fasting plasma glucose (10.0 +/- 0.7 to 7.5 +/- 0.6 mmol/l, P < 0.001) and HbA(1c) (7.8 +/- 0.4 to 6.7 +/- 0.3%, P < 0.001) despite increased body weight (83 +/- 3 to 86 +/- 3 kg, P < 0.001). During the 3-h insulin clamp period before glucose ingestion, pioglitazone improved R(d) (6.9 +/- 0.5 vs. 5.2 +/- 0.5 mg. kg(-1). min(- 1), P < 0.001) and insulin-mediated suppression of EGP (0.21 +/- 0.04 to 0.06 +/- 0.02 mg. kg(-1). min(-1), P < 0.01). Following pioglitazone treatment, hepatic fat content decreased from 19.6 +/- 3.6 to 10.4 +/- 2.1%, (P < 0.005), and SGU increased from 33.0 +/- 2.8 to 46.2 +/- 5.1% (P < 0.005). Pioglitazone treatment in type 2 diabetes 1) decreases hepatic fat content and improves insulin-mediated suppression of EGP and 2) augments splanchnic and peripheral tissue glucose uptake. Improved splanchnic/peripheral glucose uptake and enhanced suppression of EGP contribute to the improvement in glycemic control in patients with type 2 diabetes.
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PMID:Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. 1276 45

The efficacy and safety of combination therapy (repaglinide plus pioglitazone) was compared to repaglinide or pioglitazone in 24-week treatment of type 2 diabetes. This randomized, multicenter, open-label, parallel-group study enrolled 246 adults (age 24-85) who had shown inadequate response in previous sulfonylurea or metformin monotherapy (HbA(1c) > 7%). Prior therapy was withdrawn for 2 weeks, followed by randomization to repaglinide, pioglitazone, or repaglinide/pioglitazone. In the first 12 weeks of treatment, repaglinide doses were optimized, followed by 12 weeks of maintenance therapy. Pioglitazone dosage was fixed at 30 mg per day. Baseline HbA(1c) values were comparable (9.0% for repaglinide, 9.1% for pioglitazone, 9.3% for combination). Mean changes in HbA(1c) values at the end of treatment were -1.76% for repaglinide/pioglitazone, -0.18% for repaglinide, +0.32% for pioglitazone. Fasting plasma glucose reductions were -82 mg/dl for combination therapy, -34 mg/dl for repaglinide, -18 mg/dl for pioglitazone. Minor hypoglycemia occurred in 5% of patients for the combination, 8% for repaglinide, and 3% for pioglitazone. Weight gains for combination therapy were correlated to individual HbA(1c) reductions. In summary, for patients who had previously failed oral antidiabetic monotherapy, the combination repaglinide/pioglitazone had acceptable safety, with greater reductions of glycemic parameters than therapy using either agent alone.
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PMID:Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone. 1473 53

Glitazones are used in the treatment of type 2 diabetes as efficient insulin sensitizers. They can, however, induce peripheral edema through an unknown mechanism in up to 18% of cases. In this double-blind, randomized, placebo-controlled, four-way, cross-over study, we examined the effects of a 6-wk administration of pioglitazone (45 mg daily) or placebo on the blood pressure, hormonal, and renal hemodynamic and tubular responses to a low (LS) and a high (HS) sodium diet in healthy volunteers. Pioglitazone had no effect on the systemic and renal hemodynamic responses to salt, except for an increase in daytime heart rate. Urinary sodium excretion and lithium clearance were lower with pioglitazone, particularly with the LS diet (P < 0.05), suggesting increased sodium reabsorption at the proximal tubule. Pioglitazone significantly increased plasma renin activity with the LS (P = 0.02) and HS (P = 0.03) diets. Similar trends were observed with aldosterone. Atrial natriuretic levels did not change with pioglitazone. Body weight increased with pioglitazone in most subjects. Pioglitazone stimulates plasma renin activity and favors sodium retention and weight gain in healthy volunteers. These effects could contribute to the development of edema in some subjects treated with glitazones.
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PMID:Effects of the peroxisomal proliferator-activated receptor-gamma agonist pioglitazone on renal and hormonal responses to salt in healthy men. 1500 99

Patients with type 2 diabetes have dual defects: insulin resistance and beta-cell dysfunction. Thiazolidinediones (TZDs), a new class of oral drugs used for the treatment of type 2 diabetes, reduce insulin resistance via an action on peroxisome proliferator-activated receptors. There is also growing evidence that TZDs may preserve beta-cell function. Pioglitazone is a TZD that provides appropriate monotherapy or combination treatment for patients with type 2 diabetes. Studies of up to 32-week duration have shown that pioglitazone significantly reduces HbA1c and fasting plasma glucose when used alone or in combination with another glucose-lowering agent. Four recently published 52-week clinical trials, involving over 3700 patients with type 2 diabetes, show that pioglitazone is an effective long-term treatment, both as monotherapy and in combination with metformin or sulphonylurea. As well as maintaining glycaemic control over the long term, pioglitazone also confers benefits in terms of improvements in fasting insulin, lipid parameters, C-peptide and 32,33-split proinsulin (independent predictors of cardiovascular risk) and hypoglycaemia compared with other monotherapies or combination therapies. It is well tolerated, with a low incidence of adverse events. These long-term data support the concept that pioglitazone should be used earlier in the treatment of type 2 diabetes, either as monotherapy or as add-on therapy.
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PMID:Long-term glycaemic control with pioglitazone in patients with type 2 diabetes. 1505 68


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