Glipizide

The present research demonstrates the five novel cocrystals of glipizide (GPZ) with picolinic acid (PA), adipic acid (AA), isonicotinic
acid (INA), fumaric acid (FA) and sorbic acid (SRA). The cocrystals were prepared via green supramolecular mechanosynthesis
approach and exhibited 1:1 stoichiometric ratio. The cocrystals were characterized by thermal (DSC) and spectroscopic (PXRD, FTIR
and SSNMR) techniques. PXRD data was used to elucidate the crystal structure. GPZ-PA, GPZ-AA, GPZ-INA, GPZ-FA and GPZ-SRA
were found to be crystallized in triclinic and monoclinic crystal systems, which exist in P-1, P1 and P21 space groups. Remarkable
improvement in solubility and intrinsic dissolution rate (IDR) was observed along with significant reduction in rat blood serum
glucose level and high Cmax in comparison to GPZ.

The current practice of using calibration curves with narrow concentration ranges during bioanalysis of new chemical entities has some limitations and is time consuming. In the present study we describe a split calibration curve approach, where sample dilution and repeat analysis can be avoided without compromising the quality and integrity of the data obtained. A split calibration curve approach is employed to determine the drug concentration in plasma samples with accuracy and precision over a wide dynamic range of approximately 0.6 to 15,000 ng/ml for dapsone and approximately 1 to 25,000 ng/ml for cyclophosphamide and glipizide. A wide dynamic range of concentrations for these three compounds was used in the current study to construct split calibration curves and was successfully validated for sample analysis in a single run. Using this method, repeat analysis of samples can be avoided. This is useful for the bioanalysis of toxicokinetic studies with wide dose ranges and studies...

We recently demonstrated a beneficial effect of metformin compared with glipizide in type 2 diabetic patients regarding cardiovascular outcomes for 3-year treatment in the SPREAD-DIMCAD study. However, the potential mechanism for the clinical effects remains unclear. Here, we performed a comprehensive lipidomics study to evaluate the different lipid metabolites in serum samples obtained from participants in this study. Liquid chromatography-quadrupole time of flight-mass spectrometry was used to evaluate the different lipid metabolites in serum samples obtained from the participants (21 patients in glipizide group and 23 patients in metformin group) before and after each year of treatment (at 0 [baseline], 1, 2, and 3 years of study drug administration). A total of 118 serum lipid molecular species was identified and quantified. During treatment, metformin induced a substantially greater change in serum lipid species compared with glipizide, especially at the 2- and 3-year time poin...

Hypoglycemia is common in patients with diabetes. The risk of hypoglycemia after acute kidney injury (AKI) is not well defined. The purpose of this study was to compare the risk for postdischarge hypoglycemia among hospitalized patients with diabetes who do and do not experience AKI. We performed a propensity-matched analysis of patients with diabetes, with and without AKI, using a retrospective national cohort of veterans hospitalized between 2004 and 2012. AKI was defined as a 0.3 mg/dL or 50% increase in serum creatinine from baseline to peak serum creatinine during hospitalization. Hypoglycemia was defined as hospital admission or an emergency department visit for hypoglycemia or as an outpatient blood glucose <60 mg/dL. Time to incident hypoglycemia within 90 days postdischarge was examined using Cox proportional hazards models. Prespecified subgroup analyses by renal recovery, baseline chronic kidney disease, preadmission drug regimen, and HbA were performed. We identified ...

RESULTS—One patient in the sibutramine group was excluded during the study period because of hypertension; thus, a total of 29 data sets were analyzed for this group. In the placebo group, five patients had to be excluded because of low treatment efficacy, leaving a total ...