Metformin is generally recommended as a first line treatment as there is some evidence that it decreases mortality; however, this conclusion is questioned. Metformin should not be used in those with severe kidney or liver problems.A second oral agent of another class or insulin may be added if metformin is not sufficient after three months. Other classes of medications include: sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, SGLT2 inhibitors, and glucagon-like peptide-1 analogs. As of 2015 there was no significant difference between these agents. A 2018 review found that SGLT2 inhibitors and GLP-1 agonists, but not DPP-4 inhibitors, were associated with lower mortality than placebo or no treatment.Rosiglitazone, a thiazolidinedione, has not been found to improve long-term outcomes even though it improves blood sugar levels. Additionally it is associated with increased rates of heart disease and death.The effects of Plioglitazone have been compared in a Cochrane systematic review to that of other blood sugar lowering-medicine, including metformin, acarbose, and repaglinide, not showing any benefit in reducing the chance of developing type 2 diabetes in people at risk. It did, however, show reduction of risk of developing type 2 diabetes when compared to a placebo or to no treatment. These results should be interpreted considering that most of the data of the studies included in this review were of low or very-low certainty. Injections of insulin may either be added to oral medication or used alone. Most people do not initially need insulin.
Although European health professionals and scientists preferentially use the term adrenaline, the converse is true among American health professionals and scientists. Nevertheless, even among the latter, receptors for this substance are called adrenergic receptors or adrenoceptors, and pharmaceuticals that mimic its effects are often called adrenergics. The history of adrenaline and epinephrine is reviewed by Rao. Mechanism of Action
As a hormone, adrenaline acts on nearly all body tissues by binding to adrenergic receptors. Its effects on various tissues depend on the type of tissue and expression of specific forms of adrenergic receptors. For example, high levels of adrenaline cause smooth muscle relaxation in the airways but causes contraction of the smooth muscle that lines most arterioles. Adrenaline is a nonselective agonist of all adrenergic receptors, including the major subtypes α1, α2, β1, β2, and β3. Adrenalines binding to these receptors triggers a number of metabolic changes. Binding to α-adrenergic receptors inhibits insulin secretion by the pancreas, stimulates glycogenolysis in the liver and muscle, and stimulates glycolysis and inhibits insulin-mediated glycogenesis in muscle. β adrenergic receptor binding triggers glucagon secretion in the pancreas, increased adrenocorticotropic hormone (ACTH) secretion by the pituitary gland, and increased lipolysis by adipose tissue. Together, these effects increase blood glucose and fatty acids, providing substrates for energy production within cells throughout the body.Adrenaline causes liver cells to release glucose into the blood, acting through both alpha and beta-adrenergic receptors to stimulate glycogenolysis.