Effect of pioglitazone on insulin secretion in patients with both impaired fasting glucose and impaired glucose tolerance

Medical Research Unit in Clinical Epidemiology, Hospital of Specialties, Medical Unit of High Specialty, West National Medical Center, Mexican Institute of Social Security, Guadalajara, Mexico.
Diabetes Research and Clinical Practice (Impact Factor: 2.54). 02/2007; 75(1):115-8. DOI: 10.1016/j.diabres.2006.05.003
Source: PubMed

ABSTRACT To evaluate the effect of a thiazolidinedione, pioglitazone, on insulin secretion in patients with both impaired fasting glucose and impaired glucose tolerance.
A randomized, double-blind, placebo-controlled clinical trial was carried out in 18 overweight or obese patients with both impaired fasting glucose and impaired glucose tolerance. Pharmacological intervention consisted of an oral morning administration of pioglitazone (30 mg) or a placebo with a similar presentation for 30 days. Before and after the intervention, glucose, creatinine, lipid profile and uric acid concentrations were measured. To evaluate insulin secretion (early, late and total phases) and insulin sensitivity, a hyperglycemic-hyperinsulinemic clamp was also performed.
There were significant reductions (p=0.008) in fasting insulin concentration (121 versus 45 pmol/l), late (565 versus 307 pmol/l) and total insulin secretion (474 versus 254 pmol/l), as well as, in 2h postload glucose levels (9.7 versus 6.9 mmol/l, p=0.028), with an increment in insulin sensitivity after pioglitazone administration (7.5 versus 9.9).
Pioglitazone administration during a period of 4 weeks decreased late and total insulin secretion phases, fasting insulin and 2h postload glucose levels, and improved insulin sensitivity in patients with both impaired fasting glucose and impaired glucose tolerance.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this meta-analysis of randomized clinical trials (RCT) was to assess whether pioglitazone is also associated with increased cardiovascular risk, as recently reported for rosiglitazone. RCT of pioglitazone were retrieved from Medline (any date up to 31 August 2007; English language only). Unpublished RCT were identified through or websites, and results on cardiovascular outcomes were retrieved from investigators and/or sponsors, whenever possible. RCT were included in meta-analysis if pioglitazone was compared with other treatments (placebo, active comparators or no treatment) for at least 4 weeks. Ninety-four trials, 10 of which were unpublished, were retrieved; those included in the analysis, which excluded PROspective PioglitAzone Clinical Trial In MacroVascular Events (PROACTIVE), enrolled 11 268 and 9912 patients in the pioglitazone and comparator groups respectively. Data for analysis, extracted independently by two observers, included all-cause and cardiovascular mortality and incidence of non-fatal coronary events and heart failure. Proportions of outcome measures across treatment groups were compared by odds ratios (ORs) and 95% confidence interval. Pioglitazone was associated with reduced all-cause mortality [OR 0.30 (0.14-0.63); p < 0.05], with no relevant effect on non-fatal coronary events. The observed increase in incidence of non-fatal heart failure was not statistically significant [OR 1.38 (0.90-2.12)]. The use of pioglitazone does not appear to be harmful in terms of cardiovascular events and all-cause deaths.
    Diabetes Obesity and Metabolism 12/2008; 10(12):1221-38. DOI:10.1111/j.1463-1326.2008.00892.x · 5.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To assess the effect of diacerein on insulin secretion and metabolic control in drug-naïve patients with type 2 diabetes. A randomized, double-blind, placebo-controlled clinical trial was carried out in 40 drug-naïve adult patients with type 2 diabetes. A metabolic profile including interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and fasting insulin levels was carried out before the intervention and 2 months afterward. A hyperglycemic-hyperinsulinemic clamp technique was performed to assess the phases of insulin secretion and insulin sensitivity. After randomization, 20 patients received diacerein (50 mg once daily) for the first 15 days and twice daily for 45 additional days. The remaining patients received placebo. Intra- and intergroup differences were calculated by Wilcoxon signed rank and Mann-Whitney U tests. There were significant increases in first (102±63 vs. 130±75 pmol/L; P<0.01), late (219±111 vs. 280±135 pmol/L; P<0.01), and total insulin (178±91 vs. 216±99 pmol/L; P<0.01) secretions without changes in insulin sensitivity after diacerein administration. There were significant decreases in fasting glucose (7.9±1.4 vs. 6.8±1.0 mmol/L; P<0.01) and in A1C levels (8.3±1.0 vs. 7.0±0.8%; P<0.001) after diacerein administration. There were no significant changes after placebo administration in the above-mentioned evaluations. Insulin secretion increased and metabolic control improved after diacerein administration in drug-naïve patients with type 2 diabetes.
    Diabetes care 05/2011; 34(7):1591-4. DOI:10.2337/dc11-0357 · 8.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Several classes of drugs have been developed to treat type 2 diabetes mellitus (T2DM). Pioglitazone is now the only thiazolidinedione approved for the treatment of T2DM and can be administered in combination with metformin, sulfonylureas, exenatide, dipeptidyl peptidase 4 (DPP-4) inhibitors or insulin. It improves glycemic control with an extremely low incidence of hypoglycemia. In addition to reducing insulin resistance, it may also improve pancreatic beta-cell secretory function. Moreover, it exhibits a variety of favorable pleiotropic effects. The latter include anti-inflammatory, antioxidant, vasoprotective, antihypertensive and hypolipidemic actions. Finally, this agent has been shown to improve experimental diabetic neuropathy and alleviate neuropathic pain, as well as decreasing urinary albumin excretion in patients with diabetes. Thus, pioglitazone emerges as a valuable hypoglycemic agent for combination therapy in T2DM. Importantly, however, patients should be appropriately selected, especially to avoid those with heart failure, in order to minimize adverse events attributable to water retention.
    Expert Opinion on Pharmacotherapy 07/2011; 12(10):1457-61. DOI:10.1517/14656566.2011.568477 · 3.09 Impact Factor