IntroductionErtugliflozin is a sodium-glucose cotransporter 2 inhibitor in development for type 2 diabetes mellitus (T2DM). The safety and efficacy of ertugliflozin were evaluated over 52 weeks in patients with chronic kidney disease (CKD).MethodsIn this double-blind randomized study (NCT01986855), patients with glycated hemoglobin (A1C) 7.0–10.5% and stage 3 CKD [estimated glomerular filtration rate (eGFR) ≥ 30 to < 60 mL/min/1.73 m2] who were undergoing treatment with standard diabetes therapy (or therapies) including insulin and/or sulfonylureas were randomized to once-daily ertugliflozin 5 mg, 15 mg, or placebo. Patients on metformin underwent a pre-randomization ≥ 10-week wash-off period. The primary endpoint was change from baseline in A1C at week 26 in the overall cohort. Secondary efficacy endpoints were assessed in the stage 3A CKD cohort (eGFR ≥ 45 to < 60 mL/min/1.73 m2) at weeks 26 and 52. Safety was assessed in the overall cohort.Results468 patients were randomized (baseline mean A1C 8.2%). At week 26, reductions from baseline in A1C were observed across groups in the overall cohort [least squares mean changes (95% confidence interval) – 0.3% (– 0.4, – 0.1), – 0.3% (– 0.4, – 0.1), and – 0.4% (– 0.6, – 0.3) for placebo and for ertugliflozin 5 mg and 15 mg, respectively]. Prohibited use of metformin was identified in ~ 17% of patients and impacted evaluation of the primary endpoint. Greater reductions from baseline in body weight, fasting plasma glucose, and systolic blood pressure were observed with ertugliflozin versus placebo at week 26 (stage 3A CKD cohort). The incidences of urinary tract infections, genital mycotic infections, and hypoglycemia adverse events were not meaningfully different between groups. The incidence of hypovolemia-related adverse events was higher with ertugliflozin relative to placebo.ConclusionAlthough surreptitious metformin use impacted the primary analysis, reductions in blood glucose and body weight were observed with ertugliflozin in patients with T2DM and stage 3 CKD; ertugliflozin had an acceptable safety profile.FundingMerck Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and Pfizer Inc.Trial RegistrationClinicaltrials.gov identifier NCT01986855.Electronic supplementary materialThe online version of this article (10.1007/s13300-017-0337-5) contains supplementary material, which is available to authorized users.

In object substitution masking (OSM) a surrounding mask (typically comprising of 4 dots) onsets with a target but lingers after offset; under such conditions, the ability to perceive the target can be significantly reduced. OSM was originally claimed to occur only when a target was not the focus of attention, for instance, when embedded in an array of distractors (Di Lollo, Enns, & Rensink, 2000). It was argued that the distractors influenced the time taken for focal attention to reach the target. Some recent work, however, failed to find any such distractor influence; the effect of mask duration was found to be independent of set size when steps were taken to avoid ceiling effects in the smallest set size condition (Argyropoulos, Gellatly, Pilling, & Carter, 2013; Filmer, Mattingley, & Dux, 2014). In 3 experiments, we repeatedly found that set size manipulations can interact with mask duration (in which neither ceiling nor floor effects are evident), with the effect of the mask on target perceptibility being amplified according to the number of distractor items. However, a further experiment (Experiment 4) showed that crowding by nearby distractors was actually responsible for this "set size" effect. When decoupled from crowding, set size alone did not interact with masking, though it did influence overall accuracy. Thus, the presence of distractors does influence OSM, but not in the way originally assumed by Di Lollo and colleagues in their model. The Crowding × OSM interaction suggests that the 2 phenomena involve partly overlapping mechanisms.

No abstract

No abstract