Sitagliptin was developed byMerck & Co. and approved for medical use in the United States in 2006.[8] In 2023, it was the 123rd most commonly prescribed medication in the United States, with more than 5million prescriptions.[11][12] It is available as ageneric medication, but not in the United States.[13][14][15]
Sitagliptin should not be used to treat type 1 diabetes. In December 2020, the USFood and Drug Administration (FDA) approved labeling changes stating that Januvia (sitagliptin), Janumet (sitagliptin and metformin hydrochloride), and Janumet XR (sitagliptin and metformin hydrochloride extended-release) are not proven to improve glycemic (blood sugar) control in children aged 10 to 17 with type 2 diabetes.[17] The drugs are approved to improve blood sugar control in adults aged 18 and older with type 2 diabetes.[17]
The existence of rare case reports ofkidney failure and hypersensitivity reactions is noted in the United States prescribing information, but a causative role for sitagliptin has not been established.[2]
Severalpostmarketing reports ofpancreatitis (some fatal) have been made in people treated with sitagliptin and other DPP-4 inhibitors,[23][24] and the US FDA package insert carries a warning to this effect,[2] although the causal link between sitagliptin and pancreatitis has not yet been fully substantiated.[25] 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.[26]
In 2015, the US Food and Drug Administration (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.[27]
Sitagliptin works tocompetitively inhibit theenzyme dipeptidyl peptidase 4 (DPP-4). This enzyme breaks down theincretinsGLP-1 and GIP,gastrointestinal hormones released in response to a meal.[28] 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.[medical citation needed] This drives blood glucose levels towards normal.[medical citation needed] 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 (hypoglycemia), which is seen with some other oral hypoglycemic agents.[medical citation needed]
Sitagliptin has been shown to lowerHbA1c level by about 0.7% points versus placebo. It is slightly less effective than metformin when used as amonotherapy. It does not cause weight gain and has less hypoglycemia compared to sulfonylureas. Sitagliptin is recommended as a second-line drug (in combination with other drugs) after the combination of diet/exercise and metformin fails.[29]
Sitagliptin was approved by the USFood and Drug Administration (FDA) in October 2006,[30] and is sold under the brand name Januvia.[31] In April 2007, the FDA approved an oral combination ofsitagliptin/metformin sold under the brand name Janumet.[32] In October 2011, the FDA approved an oral combination ofsitagliptin/simvastatin sold under the brand name Juvisync.[33][16] The extended release version of sitagliptin/metformin was approved in February 2012.[34]
^abHerman GA, Stevens C, van Dyck K, Bergman A, Yi B, De Smet M, et al. (December 2005). "Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses".Clinical Pharmacology and Therapeutics.78 (6):675–688.doi:10.1016/j.clpt.2005.09.002.PMID16338283.S2CID20935646.{{cite journal}}: CS1 maint: overridden setting (link)
^Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W, et al. (August 2006). "Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects".Journal of Clinical Pharmacology.46 (8):876–886.doi:10.1177/0091270006289850.PMID16855072.S2CID45849328.{{cite journal}}: CS1 maint: overridden setting (link)
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