Sitagliptin

Overview

Sitagliptin, sold under the brand name Januvia among others, is an anti-diabetic medication used to treat type 2 diabetes. It is in the dipeptidyl peptidase-4 (DPP-4) inhibitor class and works by increasing the production of insulin and decreasing the production of glucagon by the pancreas. In the United Kingdom it is listed as less preferred than metformin or a sulfonylurea. It is taken by mouth. It is also available in the fixed-dose combination medication sitagliptin/metformin (Janumet, Janumet XR).[1][2] WP

Common side effects include headaches, swelling of the legs, and upper respiratory tract infections. Serious side effects may include angioedema, low blood sugar, kidney problems, pancreatitis, and joint pain. Whether use in pregnancy or breastfeeding is safe is unclear.[1][3] WP

Sitagliptin was developed by Merck & Co. and approved for medical use in the United States in 2006. In 2023, it was the 123rd most commonly prescribed medication in the United States, with more than 5 million prescriptions. It is available as a generic medication, but not in the United States.[1][4–8] WP

Uses, dosage and effects

Medical uses

Sitagliptin is used to treat type 2 diabetes. It is generally less preferred than metformin or sulfonylureas. It is taken by mouth. It is also available as the fixed-dose combinations of sitagliptin/metformin (Janumet, Janumet XR) and sitagliptin/simvastatin (Juvisync).[1][2][9] WP

Sitagliptin should not be used to treat type 1 diabetes. In December 2020, the US 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. The drugs are approved to improve blood sugar control in adults aged 18 and older with type 2 diabetes.[10] WP

Risks and side effects

Adverse effects

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.[11–15] WP

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.[16] WP

Several postmarketing reports of pancreatitis (some fatal) have been made in people treated with sitagliptin and other DPP-4 inhibitors, and the US FDA 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.[16–20] WP

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.[21] WP

Pharmacology

Mechanism of action

Sitagliptin works to competitively inhibit the enzyme dipeptidyl peptidase 4 (DPP-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 (hypoglycemia), which is seen with some other oral hypoglycemic agents.[22] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

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 (in combination with other drugs) after the combination of diet/exercise and metformin fails.[23] WP

History

History

Sitagliptin was approved by the US Food and Drug Administration (FDA) in October 2006, and is sold under the brand name Januvia. In April 2007, the FDA approved an oral combination of sitagliptin/metformin sold under the brand name Janumet. In October 2011, the FDA approved an oral combination of sitagliptin/simvastatin sold under the brand name Juvisync. The extended release version of sitagliptin/metformin was approved in February 2012.[9][24–28] WP

Chemistry

Formula

C16H15F6N5O PC

CAS number

486460-32-6 PC

Molar mass (g/mol)

407.31 PC

IUPAC name (computed by PubChem)

(3R)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one PC

SMILES

C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)C[C@@H](CC3=CC(=C(C=C3F)F)F)N PC

InChIKey

MFFMDFFZMYYVKS-SECBINFHSA-N PC

PubChem CID

4369359

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Sitagliptin Monograph for Professionals
2. Other British national formulary: BNF 76. 2018
3. Other Sitagliptin Pregnancy and Breastfeeding Warnings
4. Other Top 300 of 2023
5. Other Sitagliptin Drug Usage Statistics, United States, 2014 - 2023
6. Other Generic Januvia Availability
7. Other JAMP Pharma Group receives Health Canada approval for PrJAMP Sitagliptin, a new generic alternative for the treatment of type 2 diabetes. January 6, 2023
8. Journal / agency Sitagliptin SUN EPAR. December 9, 2021
9. Journal / agency FDA Approves Combination Therapy Juvisync. October 7, 2011
10. Journal / agency Diabetes drug not proven to improve blood sugar in pediatric patients. December 4, 2020
11. Other Januvia Side Effects & Drug Interactions. 2007
12. Journal / agency Zhao Q, Hong D, Zheng D, Xiao Y, Wu B. Risk of diarrhea in patients with type 2 diabetes mellitus treated with sitagliptin: a meta-analysis of 30 randomized clinical trials. Drug Design, Development and Therapy. 2014. doi:10.2147/DDDT.S70945 · PMID 25419118 · PMC4234286
13. Journal / agency Stricklin SM, Stoecker WV, Rader RK, Hood AF, Litt JZ, Schuman TP. Persistent edematous-plaque photosensitivity observed with sitagliptin phosphate (Januvia®). Dermatology Online Journal. February 2012. doi:10.5070/D30D70K7B2 · PMID 22398230
14. Other Januvia side effect: Photosensitivity reaction - eHealthMe
15. Journal / agency Salvo F, Moore N, Arnaud M, Robinson P, Raschi E, De Ponti F, Bégaud B, Pariente A. Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: systematic review and meta-analysis. BMJ. May 2016. doi:10.1136/bmj.i2231 · PMID 27142267 · PMC4854021
16. Journal / agency Januvia- sitagliptin tablet, film coated
17. Journal / agency Olansky L. Do incretin-based therapies cause acute pancreatitis?. Journal of Diabetes Science and Technology. January 2010. doi:10.1177/193229681000400129 · PMID 20167189 · PMC2825646
18. Journal / agency 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. June 21, 2019
19. Other National Prescribing Service. Sitagliptin for Type 2 Diabetes. August 2010
20. Journal / agency Matveyenko AV, Dry S, Cox HI, Moshtaghian A, Gurlo T, Galasso R, Butler AE, Butler PC. Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin. Diabetes. July 2009. doi:10.2337/db09-0058 · PMID 19403868 · PMC2699878
21. Journal / agency DPP-4 Inhibitors for Type 2 Diabetes: Drug Safety Communication—May Cause Severe Joint Pain. August 28, 2015
22. Journal / agency Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W, Chen L, Snyder K, Hilliard D, Tanen M, Tanaka W, Meehan AG, Lasseter K, Dilzer S, Blum R, Wagner JA. Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. Journal of Clinical Pharmacology. August 2006. doi:10.1177/0091270006289850 · PMID 16855072
23. Journal / agency Gadsby R. Efficacy and Safety of Sitagliptin in the Treatment of Type 2 Diabetes. Clinical Medicine: Therapeutics. 2009. doi:10.4137/CMT.S2313
24. Journal / agency FDA Approves New Treatment for Diabetes. October 17, 2006
25. Journal / agency Drug Approval Package: Januvia (Sitagliptin Phosphate) NDA #021995
26. Journal / agency Drug Approval Package: Janumet (Sitagliptin/Metformin Hydrochloride) NDA #022044. July 8, 2008
27. Journal / agency Drug Approval Package: Juvisync (sitagliptin and simvastatin fixed-dose combination) Tablets NDA #202343. July 13, 2012
28. Journal / agency Drug Approval Package: Janumet XR (sitagliptin/metformin hydrochloride) NDA #202270. September 3, 2013

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.