Since enolase is the penultimate step in glycolysis, if it were inhibited (for example by being bound by autoantibodies), one would expect decreased energy production by each cell, leading to resulting atrophy of the affected organ.This would occur most likely through each cell shrinking in size in response to the energy deficit (and/or in extreme situations from some cells dying via either apoptosis or necrosis, depending on location). This may occur as a result of enough ATP not being available to maintain cellular functions - notably, failure of the Na/K ATPase, resulting in a loss of the gradient to drive the Na/Ca antiporter, which normally keeps Ca+2 out of cells so it does not build to toxic levels that will rupture cell lysosomes leading to apoptosis. An additional feature of a low-energy state is failure to maintain axonal transport via dynein/kinesin ATPases, which in many diseases results in neuronal injury to both the brain and/or periphery. Pathology
Very little is known about the pathology of Hashimotos encephalopathy. Post mortem studies of some individuals have shown lymphocytic vasculitis of venules and veins in the brain stem and a diffuse gliosis involving gray matter more than white matter.As mentioned above, autoantibodies to alpha-enolase associated with Hashimotos encephalopathy have thus far been the most hypothesized mechanism of injury.
Adverse reactions for at least 5% of people taking it were hypoglycemia, nausea, nasopharyngitis, diarrhea, upper respiratory tract infections, and headache. In Study A (N=469), symptoms of hypoglycemia were recorded in 25.6% of people with zero cases of severe symptomatic hypoglycemia. Study B (N=365) had a 40% incidence of hypoglycemic events with 1.1% incidence of severe hypoglycemia requiring assistance. Interactions
Lixisenatide and other GLP-1 receptor agonist slow emptying of stomach contents, which may affect the absorption of orally administered medications. For effective use, oral contraceptives should be taken 1 hour before or 11 hours after taking lixisenatide-containing products. Acetaminophen and antibiotics are among other drugs that are affected by this action of lixisenatide. History
Lixisenatide is a GLP-1 receptor agonist that was created by Zealand Pharma A/S of Denmark; in 2003 Zealand licensed it to Sanofi which developed the drug. Lixisenatide was approved by the European Commission on February 1, 2013. Sanofi submitted an NDA in the US, which was accepted for review by the US FDA in February 2013 but after discussions with the FDA about the cardiovascular safety data included in the package (starting in 2008, the FDA had required stronger CV safety data for new anti-diabetes drugs, following the controversy around the risks of Avandia) Sanofi decided to withdraw the NDA and wait for the results of a Phase III study that was scheduled to be completed in 2015.