Glucagon is a polypeptide hormone identical to human glucagon that increases blood glucose and relaxes smooth muscle of the gastrointestinal tract. Glucagon is synthesized in a special non-pathogenic laboratory strain of Escherichia coli bacteria that has been genetically altered by the addition of the gene for glucagon. Glucagon generally elevates the concentration of glucose in the blood by promoting gluconeogenesis and glycogenolysis. Glucagon also decreases fatty acid synthesis in adipose tissue and the liver, as well as promoting lipolysis in these tissues, which causes them to release fatty acids into circulation where they can be catabolised to generate energy in tissues such as skeletal muscle when required. Glucose is stored in the liver in the form of the polysaccharide glycogen, which is a glucan (a polymer made up of glucose molecules). Liver cells (hepatocytes) have glucagon receptors. When glucagon binds to the glucagon receptors, the liver cells convert the glycogen into individual glucose molecules and release them into the bloodstream, in a process known as glycogenolysis. As these stores become depleted, glucagon then encourages the liver and kidney to synthesize additional glucose by gluconeogenesis. Glucagon turns off glycolysis in the liver, causing glycolytic intermediates to be shuttled to gluconeogenesis. Glucagon also regulates the rate of glucose production through lipolysis. Glucagon induces lipolysis in humans under conditions of insulin suppression (such as diabetes mellitus type 1). Glucagon increases blood glucose concentration and is used in the treatment of hypoglycemia. Glucagon administered through a parenteral route relaxes smooth muscle of the stomach, duodenum, small bowel, and colon. Glucagon is also indicated as a diagnostic aid in the radiologic examination of the stomach, duodenum, small bowel, and colon when diminished intestinal motility would be advantageous.

Saxagliptin is an orally active hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. FDA approved on July 31, 2009. Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor antidiabetic for the treatment of type 2 diabetes. DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver. [Bristol-Myers Squibb Press Release] DPP-4 is a membrane associated peptidase which is found in many tissues, lymphocytes and plasma. DPP-4 has two main mechanisms of action, an enzymatic function and another mechanism where DPP-4 binds adenosine deaminase, which conveys intracellular signals via dimerization when activated. Saxagliptin forms a reversible, histidine-assisted covalent bond between its nitrile group and the S630 hydroxyl oxygen on DPP-4. The inhibition of DPP-4 increases levels active of glucagon like peptide 1 (GLP-1), which inhibits glucagon production from pancreatic alpha cells and increases production of insulin from pancreatic beta cells.

Pioglitazone (brand name Actos) is a prescription drug of the thiazolidinedione class with hypoglycemic action used in the treatment of type 2 diabetes. Pioglitazone selectively stimulates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and to a lesser extent PPAR-α. It modulates the transcription of the genes involved in the control of glucose and lipid metabolism in the muscle, adipose tissue, and the liver. As a result, pioglitazone reduces insulin resistance in the liver and peripheral tissues, decreases gluconeogenesis in the liver, and reduces the quantity of glucose and glycated hemoglobin in the bloodstream. Pioglitazone is used to lower blood glucose levels in the treatment of diabetes mellitus type 2 (T2DM) either alone or in combination with a sulfonylurea, metformin, or insulin. Pioglitazone cannot be used in patients with a known hypersensitivity to pioglitazone, other thiazolidinediones or any of components of its pharmaceutical forms. It is ineffective and possibly harmful to diabetes mellitus type 1 and diabetic ketoacidosis. Pioglitazone can cause fluid retention and peripheral edema. As a result, it may precipitate congestive heart failure (which worsens with fluid overload in those at risk). It may cause anemia. Mild weight gain is common due to increase in subcutaneous adipose tissue. In studies, patients on pioglitazone had an increased proportion of upper respiratory tract infection, sinusitis, headache, myalgia and tooth problems.