In this study in patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitagliptin concentration of 100 nm or greater, and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT.

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The prospective, multicenter, double-blind study presented in this report evaluated whether or not intravenous (IV) administration of doripenem, a carbapenem with bactericidal activity against gram-negative and gram-positive uropathogens, is inferior to IV administration of levofloxacin in the treatment of complicated urinary tract infection (cUTI). Patients (n ‫؍‬ 753) with complicated lower UTI or pyelonephritis were randomly assigned to receive IV doripenem at 500 mg every 8 h (q8h) or IV levofloxacin at 250 mg q24h. Patients in both treatment arms were eligible to switch to oral levofloxacin after 3 days of IV therapy to complete a 10-day treatment course if they demonstrated significant clinical and microbiological improvements. The microbiological cure rate (primary end point) was determined at the test-of-cure (TOC) visit occurring 5 to 11 days after the last dose of antibiotic. For the microbiologically evaluable patients (n ‫؍‬ 545), the microbiological cure rates were 82.1% and 83.4% for doripenem and levofloxacin, respectively (95% confidence interval [CI] for the difference, ؊8.0 to 5.5%); in the microbiological modified intent-to-treat cohort (n ‫؍‬ 648), the cure rates were 79.2% and 78.2%, respectively. Clinical cure rates at the TOC visit were 95.1% in the doripenem arm and 90.2% in the levofloxacin arm (95% CI around the difference in cure rates [doripenem cure rate minus levofloxacin cure rate], 0.2% to 9.6%). Both treatment regimens were generally well tolerated. Doripenem was found not to be inferior to levofloxacin in terms of therapeutics and is now approved for use in the United States and Europe for the treatment of adults with cUTI, including pyelonephritis. As fluoroquinolone resistance increases, doripenem may become a more important option for successful treatment of cUTIs, including treatment of pyelonephritis.