Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

During the last decade, oral cyclosporin (CsA) has proven to be effective, in randomized controlled trials, for the treatment of atopic dermatitis (AD) in human patients. The purpose of this blinded randomized controlled trial was to test the hypothesis that CsA was successful in reducing the gravity of clinical signs of AD in dogs. Thirty dogs with nonseasonal AD were randomly allocated to receive an oral solution of either NEORAL CsA (5 mg kg-1) or prednisolone (0.5 mg kg-1) once daily for 6 weeks. Before, and 3 and 6 weeks after therapy, skin lesions were graded by clinicians using the Canine AD Extent and Severity Index (CADESI). Pruritus was assessed by the owners using a visual analog scale (PVAS). In both groups, CADESI and PVAS values were significantly lower at 6 weeks post treatment than before the initiation of therapy (Friedman test, P < 0.0004). The percentage reductions in CADESI and PVAS values from baseline were not statistically different between groups (Mann-Whitney test, P > 0.3). In this experiment, the tolerability and safety of oral CsA and prednisolone appeared similar. One-fifth of dogs given oral CsA occasionally developed diarrhoea or soft stools. One dog that was given CsA developed a generalized papillomatous skin eruption during the second half of the trial. Our study provides randomized controlled trial evidence that CsA reduces the severity of clinical signs in dogs with nonseasonal AD. Moreover, the anti-allergic efficacy of CsA appears comparable with that of prednisolone. We propose that oral CsA should be considered as a valuable alternative to glucocorticoid therapy in dogs with AD.

In this pilot investigation, the TCC group exhibited improvements in HRQL and self-esteem from baseline to 6 and 12 weeks, while the support group exhibited declines. Randomized, controlled clinical trials with larger sample sizes are needed.

A total of 52 weeks of therapy with RSG (4 mg b.i.d.) did not adversely affect cardiac structure or function in patients with type 2 diabetes and produced significant and sustained reductions in hyperglycemia. Decreases in ambulatory diastolic blood pressure with RSG were superior to those with GLB.

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In canine and human atopic patients, the intracutaneous injection of offending allergens is followed by the development of both immediate and late-phase reactions. The present study was performed to expand on the characterization and dynamics of inflammatory cell subsets during IgE-mediated late-phase reactions in canine skin. Three normal dogs and three Dermatophagoides farinae-allergic dogs were selected for this experiment. All dogs were challenged intradermally with mite allergen, purified anticanine IgE antibodies (positive control) or phosphate-buffered saline (negative control). Skin biopsies were obtained before and 6, 12 and 24 h post-injection. Sections were stained with metachromatic and eosinophil-specific histological stains. Additionally, we used an immunohistochemical method with antibodies specific for canine leukocyte antigens. This study confirmed the occurrence of a late-phase reaction in atopic skin following allergen challenge, and in normal and atopic canine skin after intradermal injection of IgE-specific antibodies. Whereas early emigrating dermal cells were composed chiefly of neutrophil and activated eosinophil granulocytes, there was an influx of alpha beta T-lymphocytes and dermal dendritic cells in later stages of the late-phase reactions. Because IgE-mediated late-phase reactions resemble spontaneous atopic canine skin lesions, both at macroscopic and microscopic levels, we propose the use of similar challenges to study the anti-inflammatory effects of anti-allergic drugs in a pre-clinical setting.

Cholecystokinin (CCK) decreases meal size through activation of CCK-A receptors on vagal afferents. We tested the hypothesis that the selective CCK-A agonist GI181771X induces weight loss in obese patients. Patients with body mass index > or = 30 or > or = 27 kg/m2 with concomitant risk factors were randomized to 24-week, double-blind treatment with different GI181771X doses or matching placebo together with a hypocaloric diet. The primary efficacy end point was the absolute change in body weight. To monitor pancreatic and gallbladder effects, patients underwent abdominal ultrasound and magnetic resonance imaging before and after treatment. We randomized 701 patients to double-blind treatment. GI181771X did not reduce body weight and had no effect on waist circumference or other cardiometabolic risk markers. Gastrointestinal side effects were more common with GI181771X than with placebo treatment, whereas hepatobiliary or pancreatic abnormalities did not occur. CCK-A by itself does not have a central role in long-term energy balance.