Pioglitazone Metabolic Effect in Metformin-Intolerant Obese Patients Treated with Sibutramine

Objective: Metformin is the drug of choice to treat obese type 2 diabetes patients because it reduces either insulin-resistance and body weight. We aimed to comparatively test the efficacy and tolerability of pioglitazone and sibutramine in metformin-intolerant obese type 2 diabetic patients treated with sibutramine. Materials and Methods: Five hundred and seventy-six consecutive Caucasian obese type 2 diabetic patients were evaluated during a 12-months period and fifty-two patients were resulted intolerant to metformin at maximum dosage (3,000 mg/day). All intolerant patients to metformin received a treatment with pioglitazone (45 mg/day) and sibutramine (10 mg/day) and they were compared with fifty-three patients treated with metformin (3,000 mg/day) and sibutramine (10 mg/day) for 6 months in a single-blind controlled trial. We assessed body mass index, waist circumference, glycated hemoglobin, Fasting Plasma glucose, postprandial plasma glucose, fasting plasma insulin, postprandial plasma insulin, lipid profile, systolic blood pressure, diastolic blood pressure and heart rate at baseline and after 3, and 6 months. Results: No body mass index change was observed at 3, and 6 months in pioglitazone + sibutramine group, while a significant reduction of body mass index and waist circumference was observed after 6 months in metformin + sibutramine group (p<0.05). A significant decrease of glycated hemoglobin, Fasting Plasma glucose, postprandial plasma glucose, fasting plasma insulin, postprandial plasma insulin and HOMA index was observed after 3, and 6 months in both groups (p<0.05, and p<0.01, respectively). A significant Tg reduction was present after 6 months (p<0.05) in both groups respect to the baseline values. No systolic blood pressure, diastolic blood pressure and heart rate change was obtained after 3, and 6 months in both groups. Conclusion: Pioglitazone and sibutramine combination appears to be a short-term equally efficacious and well-tolerated therapeutic alternative respect to metformin-intolerant obese type 2 diabetic patients treated with sibutramine

Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in combined dyslipidemia.

PURPOSE: To evaluate the distribution of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and their specific inhibitors in a sample of patients affected by mild dyslipidemia but not yet treated with antihyperlipidemic drugs. METHODS: One hundred and sixty-eight Caucasian patients aged >or=18 yr of either sex with combined dyslipidemia and who had never previously taken lipid-lowering medications were evaluated. As a control population, we enrolled 179 Caucasian healthy subjects, aged >or=18 yr of either sex. We evaluated body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) Lp(a), plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct), fibrinogen (Fg), high sensitivity C-reactive protein (Hs-CRP), adiponectin (ADP), MMP-2, MMP-9, tissue inhibitors of metalloproteinase-1 (TIMP-1), and tissue inhibitors of metalloproteinase-2 (TIMP-2). RESULTS: TC, Tg, and LDL-C were higher (P < < 0.05, P < < 0.01 and P < < 0.05, respectively) in the dyslipidemic group, while HDL-C levels were lower (P < < 0.01) compared with the control group. Increases of PAI-1, Hct, Fg, and Hs-CRP (P < < 0.01, P < < 0.05, P < < 0.05, and P < < 0.05, respectively) were present in the dyslipidemic group, while ADP level was lower (P < < 0.01) in the dyslipidemic patients compared with controls. MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were higher (P < < 0.0001) in the dyslipidemic group. CONCLUSIONS: Combined hyperlipidemic patients have increased levels of prothrombotic and microinflammatory parameters and higher levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 than control subjects. The prognostic importance of this observation has to be evaluated in adequately designed prospective studies

Effects of insulin therapy with continuous subcutaneous insulin infusion (CSII) in diabetic patients: comparison with multi-day insulin injections therapy (MDI)

We compared the effects of continuous subcutaneous insulin infusion (CSII) and multi-daily insulin injections therapy (MDI) on glicemic control and on lipid profile in type 1 and type 2 diabetic patients. We divided the patients in two groups: in the first one (n=32) CSII was administered, in the second one (n=32) MDI was administered. HbA(1C) value was lower after 3, 6, 9, and 12 months with CSII compared to MDI. Fasting plasma glucose (FPG) value was lower with CSII after 3, 6, and 12 months compared to MDI. Post-prandial glucose (PPG) value was lower in the group with CSII after 3, 6, 9, and 12 months compared to MDI. A significant TC decrease was observed in the group treated with CSII at 9, and 12 months while a significant TC increase was observed with MDI at 6, and 12 months. A significant LDL-C decrease was obtained with CSII after 9, and 12 months while no significant changes were observed with MDI. A significant HDL-C increase was observed with CSII after 12 months. A significant Tg decrease was observed with CSII after 12 months while a significant Tg increase was observed with MDI at 6, and at 12 months. CSII therapy allows a faster and better achievement of the therapeutic target and also gives an improvement of the lipid profile