Sitagliptin

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Sitagliptin
Clinical data
Pronunciation/sɪtəˈɡlɪptɪn/ ⓘ
Trade namesJanuvia, Zituvio, others
AHFS/Drugs.comMonograph
MedlinePlusa606023
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability87%
Protein binding38%
MetabolismLiver (CYP3A4- and CYP2C8-mediated)
Elimination half-life8 to 14 h[6]
ExcretionKidney (80%)[6]
Identifiers
  • (R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine
JSmol)
  • Fc1cc(c(F)cc1F)C[C@@H](N)CC(=O)N3Cc2nnc(n2CC3)C(F)(F)F
  • InChI=1S/C16H15F6N5O/c17-10-6-12(19)11(18)4-8(10)3-9(23)5-14(28)26-1-2-27-13(7-26)24-25-15(27)16(20,21)22/h4,6,9H,1-3,5,7,23H2/t9-/m1/s1 checkY
  • Key:MFFMDFFZMYYVKS-SECBINFHSA-N checkY
  (verify)

Sitagliptin, sold under the brand name Januvia among others, is an

fixed-dose combination medication sitagliptin/metformin (Janumet, Janumet XR).[7]

Common side effects include headaches, swelling of the legs, and

dipeptidyl peptidase-4 (DPP-4) inhibitor class and works by increasing the production of insulin and decreasing the production of glucagon by the pancreas.[7]

Sitagliptin was developed by

generic medication in Canada but not the United States.[12][13]

Medical uses

Sitagliptin is used to treat type 2 diabetes.

fixed-dose combinations of sitagliptin/metformin (Janumet, Janumet XR)[7] and sitagliptin/simvastatin (Juvisync).[14]

Sitagliptin should not be used to treat type 1 diabetes. In December 2020, the U.S. Food 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.[15] The drugs are approved to improve blood sugar control in adults aged 18 and older with type 2 diabetes.[15]

Adverse effects

Adverse effects from sitagliptin are similar to

sulphonylureas, the risk of low blood sugar is increased.[20]

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.[2]

Several postmarketing reports of pancreatitis (some fatal) have been made in people treated with sitagliptin and other DPP-4 inhibitors,[21][22] and the U.S. package insert carries a warning to this effect,[2] although the causal link between sitagliptin and pancreatitis has not yet been fully substantiated.[23] 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.[24]

In 2015, the U.S. 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.[25]

Mechanism of action

See also:
Dipeptidyl peptidase-4 inhibitors

Sitagliptin works to

GLP-1 and GIP, gastrointestinal hormones released in response to a meal.[26] 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 lower

monotherapy. 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.[27]

History

See also:
Development of dipeptidyl peptidase-4 inhibitors

Sitagliptin was approved by the U.S. Food and Drug Administration (FDA) in October 2006,[28] and is marketed in the US as Januvia by Merck & Co. On April 2, 2007, the FDA approved an oral combination of sitagliptin/metformin sold in the US under the brand name Janumet. On October 7, 2011, the FDA approved an oral combination of sitagliptin/simvastatin marketed in the US as Juvisync.[14]

References

  1. ^ "Product monograph brand safety updates". Health Canada. February 2024. Retrieved March 24, 2024.
  2. ^ a b c "Januvia- sitagliptin tablet, film coated". DailyMed. Archived from the original on October 27, 2021. Retrieved October 15, 2021.
  3. ^ "Zituvio- sitagliptin tablet". DailyMed. November 1, 2023. Retrieved December 25, 2023.
  4. ^ "Zituvio- sitagliptin tablet". DailyMed. November 1, 2023. Retrieved December 25, 2023.
  5. ^ "Januvia EPAR". European Medicines Agency. September 17, 2018. Archived from the original on October 23, 2021. Retrieved October 15, 2021.
  6. ^
    S2CID 20935646
    .
  7. ^ a b c d e f g h i j "Sitagliptin Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on March 4, 2016. Retrieved March 3, 2019.
  8. ^
    ISBN 9780857113382
    .
  9. ^ "Sitagliptin Pregnancy and Breastfeeding Warnings". Drugs.com. Archived from the original on March 6, 2019. Retrieved March 3, 2019.
  10. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on January 15, 2024. Retrieved January 14, 2024.
  11. ^ "Sitagliptin - Drug Usage Statistics". ClinCalc. Retrieved January 14, 2024.
  12. ^ "Generic Januvia Availability". Drugs.com. Retrieved December 1, 2023.
  13. ^ "JAMP Pharma Group receives Health Canada approval for PrJAMP Sitagliptin, a new generic alternative for the treatment of type 2 diabetes" (Press release). JAMP Pharma. January 6, 2023. Retrieved June 19, 2023 – via Newswire.
  14. ^
    U.S. Food and Drug Administration. October 7, 2011. Archived from the original
    on August 24, 2014. Retrieved November 17, 2013.
  15. ^ a b "Diabetes drug not proven to improve blood sugar in pediatric patients". U.S. Food and Drug Administration. December 4, 2020. Archived from the original on December 4, 2020. Retrieved December 5, 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  16. ^ a b "Januvia Side Effects & Drug Interactions". RxList.com. 2007. Archived from the original on November 20, 2007. Retrieved November 28, 2007.
  17. PMID 25419118
    .
  18. PMID 22398230. Archived
    from the original on April 8, 2019. Retrieved June 6, 2019.
  19. ^ "Januvia side effect: Photosensitivity reaction - eHealthMe". www.ehealthme.com. Archived from the original on June 7, 2019. Retrieved June 6, 2019.
  20. PMID 27142267
    .
  21. PMID 20167189
    .
  22. ^ "FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes". U.S. Food and Drug Administration (FDA). June 21, 2019. Archived from the original on May 10, 2022. Retrieved May 10, 2022.
  23. ^ National Prescribing Service (August 2010). "Sitagliptin for Type 2 Diabetes". Archived from the original on July 18, 2010. Retrieved August 27, 2010.
  24. PMID 19403868
    .
  25. ^ "DPP-4 Inhibitors for Type 2 Diabetes: Drug Safety Communication—May Cause Severe Joint Pain". U.S. Food and Drug Administration (FDA). August 28, 2015. Archived from the original on December 13, 2019. Retrieved September 1, 2015.
  26. S2CID 45849328
    .
  27. doi:10.4137/CMT.S2313
    .
  28. ^ "FDA Approves New Treatment for Diabetes" (Press release). U.S. Food and Drug Administration (FDA). October 17, 2006. Archived from the original on February 28, 2009. Retrieved October 17, 2006.
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