The epidemics of metabolic disease, in the form of obesity and type 2 diabetes, are a growing public health concern. However, incretin-based therapeutics have transformed our ability to address these Show more
The epidemics of metabolic disease, in the form of obesity and type 2 diabetes, are a growing public health concern. However, incretin-based therapeutics have transformed our ability to address these diseases. While this current generation of incretin analogues show weight regain upon cessation of treatment, the amount of which can depend on the treatment and patient, iterative advancements may improve weight loss durability in the long term. In this review, we discuss the development of glucagon like peptide-1 receptor (GLP-1R) agonists and GLP-1R/ glucose-dependent insulinotropic polypeptide receptor (GIPR) co-agonists, and how future generations will leverage this strategy. We focus our review on glucagon receptor (GCGR) agonism, which has recently been combined with both GLP-1R and GLP-1R/GIPR agonism to generate dual (e.g. survodutide, cotatutide, mazdutide, etc) and triple agonists (e.g. retatrutide, etc) for improved body weight loss via energy expenditure stimulation. We rely on largely pre-clinical evidence for action because clinical data is extremely limited for GCGR agonism. Herein, we review mechanisms by which glucagon receptor agonists act to increase energy expenditure. Finally, we discuss future improvements to incretin-based therapeutics, and how they can include strategies that target the GCGR. The purpose of this review is to discuss mechanisms by which GCGR agonism can reduce body weight and put them in the context of the combination with incretin receptor agonists. Mechanistic data has only currently been evaluated in preclinical rodent models and evidence for similar processes in humans is limited. We also provide perspectives about how treatments can improve for future advancement of obesity treatment. Show less
The purpose of the study was to compare the susceptibility to respiratory morbidity in a cohort of 1129 9-years old children being exposed to congenital and postnatal environmental tobacco exposure wi Show more
The purpose of the study was to compare the susceptibility to respiratory morbidity in a cohort of 1129 9-years old children being exposed to congenital and postnatal environmental tobacco exposure with that of not exposed cohort. Results of the study provides strong evidence that older children who were exposed to ETS in their home environment were considerable more susceptible to acute respiratory tract illnesses than unexposed ones. As there was a dose-response relationship between degree of exposure (for lower ETS exposure OR = 1.32; for higher ETS exposure OR = 1.74) and excess rates of respiratory episodes this supports the existence of a causal explanation for the association observed. The significant trend of increased susceptibility in children to respiratory infections with the level of ETS exposure after exclusions of allergy and smoking in pregnancy suggests the existence of direct effect of ETS exposure on the child's respiratory health that is independent of atopy and in utero exposure to tobacco smoke products. Show less