Drugs of today
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When oral hypoglycemic agents do not successfully suppress hyperglycemia, the traditional approach has been to add insulin injections. With the coming of glucagon-like peptide 1 (GLP-1) receptor agonists carrying the benefits of weight loss and reduced risk of hypoglycemia, it has been suggested that GLP-1 agents should be used instead. There is equivalent lowering of HbA1c with either treatment. ⋯ Lower dosage of insulin degludec reduces the risk of hypoglycemia. Liraglutide combats the weight gain that accompanies the introduction of insulin therapy, and a reduced dose of liraglutide induces less GI intolerance. This first combined basal insulin-GLP-1 receptor agonist combination represents a conceptual advance in the treatment of insulin-requiring type 2 diabetes.
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Our increased understanding of the molecular subsets of non-small cell lung cancer (NSCLC) has led to the development of highly effective targeted therapies. In particular, the outcomes of patients with advanced NSCLC driven by the EML4-ALK fusion protein, which comprise 3-5% of cases, have remarkably improved with the use of crizotinib, an oral multi-tyrosine kinase inhibitor that targets ALK. However, patients inevitably develop progression while on crizotinib due to various mechanisms of resistance. ⋯ Due to the impressive results of early phase studies, alectinib was approved for the treatment of advanced ALK-positive NSCLC in Japan, while it has been granted a breakthrough therapy designation by the FDA. A phase III trial is currently ongoing. This review will describe the biology and significance of ALK rearrangements in NSCLC, ALK inhibition by crizotinib and mechanisms of resistance, as well as the preclinical and clinical evidence for the novel ALK inhibitor alectinib.