Amino-acid substitution at position 8 prevents chemical breakdown by dipeptidyl peptidase-4. In addition, the lysine at position 26 is in its derivative form (acylated with stearic diacid). Acylation with a spacer and C-18 fatty diacid chain increases the drugs binding to blood protein (albumin), which enables longer presence in the blood circulation. History
Semaglutide was developed in 2012, by a team of researchers at Novo Nordisk as a longer-acting alternative to liraglutide as a once-weekly diabetes therapy. It was given the brand name Ozempic. Clinical trials were started on 6 January 2016, and completed on 19 May 2017.Researchers at the University of Leeds and Novo Nordisk reported in 2017, that it can also be used for the treatment of obesity. It reduces hunger, food craving and body fat. A phase 3 randomized controlled trial found that once-weekly injection of 2.4 mg of the drug resulted in an average change of −14.9% body weight at 68 weeks compared to −2.4% for the placebo.The US FDA New Drug Application (NDA) was filed in December 2016, and in October 2017, the FDA Advisory Committee approved it unanimously. It can be administered by injection or orally.
After total ischemia occurs, the myocardium switches immediately from aerobic glycolysis to anaerobic glycolysis resulting in the reduced ability to produce high energy phosphates such as ATP and Creatinine Phosphate. At this point, the lack of the energy and lactate accumulation results in cessation of contraction within 60 seconds of ischemia (i.e. Vessel Occlusion). Subsequent to this is a period of "myocardial stunning," in which reversible ischemic damage is taking place. At approximately 30 minutes after the onset of total ischemia the damage becomes irreversible, thereby ending the phase of myocardial stunning. The generation of oxygen-derived [free radicals] during the initial period of reperfusion after ischemia is believed to contribute to the pathogenesis of myocardial stunning.Some evidence suggests that brief, repetitive episodes of myocardial ischemia may result in chronic myocardial stunning and ventricular contractile impairment. Diagnosis
Imaging techniques such as echocardiography, ventriculography, and nuclear imaging can be used to detect a contractile dysfunction following reperfusion after an episode of ischemia. The area of dysfunction should also maintain normal perfusion, detected via Positron Emission Tomography, echocardiography with contrast, and/or thallium scintigraphy in order for a diagnosis of myocardial stunning to be considered. However, there are many practical challenges to diagnosing myocardial stunning using these methods. Accurate detection of regional myocardial blood flow and contraction function abnormalities must be detected at levels of high sensitivity. The diagnosis of myocardial stunning must also be differentiated from other conditions such as hibernating myocardium and persistent (silent) subendocardial ischemia, which can also co-exist with superimposed stunning.