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.
Educating GPs in the French adaptation of the SDM programme improves glycaemic control in a primary care setting, without significantly increasing healthcare costs.
The pleiotropic effects of statins have been evaluated to assess their potential benefit in the treatment of various inflammatory and immune-mediated diseases including periodontitis. Herein, the adjunctive use of statins in periodontal therapy in vitro, in vivo, and in clinical trials was reviewed. Statins act through several pathways to modulate inflammation, immune response, bone metabolism, and bacterial clearance. They control periodontal inflammation through inhibition of proinflammatory cytokines and promotion of anti-inflammatory and/or proresolution molecule release, mainly, through the ERK, MAPK, PI3-Akt, and NF-κB pathways. Moreover, they are able to modulate the host response activated by bacterial challenge, to prevent inflammation-mediated bone resorption and to promote bone formation. Furthermore, they reduce bacterial growth, disrupt bacterial membrane stability, and increase bacterial clearance, thus averting the exacerbation of infection. Local statin delivery as adjunct to both nonsurgical and surgical periodontal therapies results in better periodontal treatment outcomes compared to systemic delivery. Moreover, combination of statin therapy with other regenerative agents improves periodontal healing response. Therefore, statins could be proposed as a potential adjuvant to periodontal therapy. However, optimization of the combination of their dose, type, and carrier could be instrumental in achieving the best treatment response.
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