Sitagliptin is used to treat diabetes mellitus type 2. It is generally less preferred than metformin or sulfonylureas. It is taken by mouth. It is also available within a single pill as metformin/sitagliptin.
Adverse effects from sitagliptin are similar to placebo, except for rare nausea, common cold-like symptoms, and photosensitivity. It does not increase the risk of diarrhea. No significant difference exists in the occurrence of hypoglycemia between placebo and sitagliptin. In those taking sulphonylureas, the risk of low blood sugar is increased. The existence of rare case reports of kidney failure and hypersensitivity reactions is noted in the United States prescribing information, but a causative role for sitagliptin has not been established. Several postmarketing reports of pancreatitis have been made in people treated with sitagliptin and other DPP-4 inhibitors, and the U.S. package insert carries a warning to this effect, although the causal link between sitagliptin and pancreatitis has not yet been fully substantiated. One study with lab rats published in 2009 concluded that some of the possible risks of pancreatitis or pancreatic cancer may be reduced when it is used with metformin. However, while DPP-4 inhibitors showed an increase in such risk factors, as of 2009, no increase in pancreatic cancer has been reported in individuals taking DPP-4 inhibitors. The updated prescribing information cautions that multiple postmarketing reports have been made of serious hypersensitivity reactions in patients receiving sitagliptin. Merck notes: In 2015, FDA added a new Warning and Precaution about the risk of "severe and disabling" joint pain to the labels of all DPP-4 inhibitor medicines. In addition to sitagliptin, other DPP-4 inhibitors such as saxagliptin, linagliptin, and alogliptin must also carry the new FDA Warning and Precaution label.
Mechanism of action
Sitagliptin works to competitively inhibit the enzymedipeptidyl peptidase 4. This enzyme breaks down the incretins GLP-1 and GIP, gastrointestinal hormones released in response to a meal. By preventing breakdown of GLP-1 and GIP, they are able to increase the secretion of insulin and suppress the release of glucagon by the alpha cells of the pancreas. This drives blood glucose levels towards normal. As the blood glucose level approaches normal, the amounts of insulin released and glucagon suppressed diminishes, thus tending to prevent an "overshoot" and subsequent low blood sugar, which is seen with some other oral hypoglycemic agents. Sitagliptin has been shown to lower HbA1c level by about 0.7% points versus placebo. It is slightly less effective than metformin when used as a monotherapy. It does not cause weight gain and has less hypoglycemia compared to sulfonylureas. Sitagliptin is recommended as a second-line drug after the combination of diet/exercise and metformin fails.
History
Sitagliptin was approved by the U.S. Food and Drug Administration on October 17, 2006, and is marketed in the US as Januvia by Merck & Co. On April 2, 2007, the FDA approved an oral combination of sitagliptin and metformin marketed in the US as Janumet. On October 7, 2011, the FDA approved an oral combination of sitagliptin and simvastatin marketed in the US as Juvisync.
