ABSTRACT
Background: On 18th June 2013, India banned pioglitazone, a peroxisome proliferation activator gamma agonist, and a popular anti-diabetic drug used in the treatment of type 2 diabetes mellitus (T2DM), but on 21st August 2013, ban was revoked after stiff opposition from diabetologists and pioglitazone was reintroduced to the market again. Aim and Objective: The aim of this study was to assess the efficacy and safety of low-dose pioglitazone compared to standard dose pioglitazone in adults with T2DM. Materials and Methods: After obtaining permission from the Institutional Ethics Committee, 50 patients with T2DM who were not under adequate glycemic control with metformin and glimepiride combination therapy were included in the study. The patients were randomly assigned (1:1) into pioglitazone 7.5 mg group and 15 mg group as an add on treatment to the existing therapy. Results: All the glycemic parameters such as Fasting blood sugar (FBS), post prandial blood glucose (PPBS), Glycosylated Hemoglobin (HbA1c) are significantly reduced in both groups from baseline to the end of 12 weeks. FBS reduced from 183.64 ± 20.9 to 152.08 ± 15.2 in the Pioglitazone 7.5 mg group and from 177.32 ± 16.89 to 145.2 ± 11.6 in the pioglitazone 15 mg group (P < 0.05), PPBS was reduced from 260.2 ± 31.09 to 213.8 ± 29.5 and from 256.24 ± 43.72 to 203.52 ± 27.5 (P < 0.05) in 7.5 mg and 15 mg group, respectively. HbA1c was reduced from 8.969 ± 0.88 to 8.508 ± 0.9 in 7.5 mg group (P < 0.05) and in 15 mg group, it was reduced from 8.796 ± 0.79 to 8.19 ± 0.72 (P < 0.05). In the study, Pioglitazone 7.5 mg efficaciously reduced glycemic parameters similar to pioglitazone 15 mg and there was no statistically significant difference between the groups. Three patients reported with pedal edema as adverse effect in pioglitazone 15 mg therapy, whereas only one in 7.5 mg pioglitazone therapy complained of ankle edema. Conclusion: Low-dose pioglitazone offers an attractive alternative option to standard dose pioglitazone as an add on therapy for T2DM due to its effectiveness in reducing glycemic markers and also fewer side effect profile.
ABSTRACT
Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.