Dipeptidyl peptidase-4 inhibitor

# Overview
Inhibitors of dipeptidyl peptidase 4, also DPP-4 inhibitors or gliptins, are anti-diabetic drugs and a class of oral hypoglycemics that block DPP-4. They can be used to treat diabetes mellitus type 2.
The first agent of the class - sitagliptin  - was approved by the FDA in 2006.
Glucagon increases blood glucose levels, and DPP-4 inhibitors reduce glucagon and blood glucose levels. The mechanism of DPP-4 inhibitors is to increase incretin levels (GLP-1 and GIP), which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels.
DPP-4 inhibitors may reduce mortality when used for treating diabetes mellitus type 2.

# Examples
Drugs belonging to this class are :
- Sitagliptin (FDA approved 2006, marketed by Merck & Co. as Januvia),
- Vildagliptin (EU approved 2007, marketed in the EU by Novartis as Galvus),
- Saxagliptin (FDA approved in 2009, marketed as Onglyza),
- Linagliptin (FDA approved in 2011, marketed as Tradjenta by Eli Lilly Co and Boehringer Ingelheim),
- Anagliptin (approved in Japan in 2012, marketed by Sanwa Kagaku Kenkyusho Co., Ltd. and Kowa Company, Ltd.)
- Teneligliptin (approved in Japan in 2012)
- Alogliptin (FDA approved 2013, marketed by Takeda Pharmaceutical Company)
- Gemigliptin (being developed by LG Life Sciences)
- Dutogliptin (being developed by Phenomix Corporation), Phase III
Other chemicals which inhibit DDP4 include:
- Berberine, the common herbal dietary supplement, too inhibits dipeptidyl peptidase-4, which at least partly explains its antihyperglycemic  activity.
- Lupeol, found in mango, red alder (Alnus rubra), and dandelion coffee.

# Risks and side effects
Adverse effects, including nasopharyngitis, headache, nausea, hypersensitivity and skin reactions, have been observed in clinical studies.

## Heart failure (possible association)
Dipeptidyl-Peptidase IV Inhibitors may or may not be associated with heart failure.

## Pancreatic cancer (possible association)
A 2013 study of the DPP-4 inhibitor sitagliptin reported found "worrisome changes in the pancreases of the rats that could lead to pancreatic cancer". A second paper by the same authors reported an increase in precancerous lesions in the pancreases of organ donors who had taken GLP-1 inhibitors. In response to these reports, the United States FDA and the European Medicines Agency each undertook independent reviews of all clinical and preclinical data related to the possible association of DPP-IV inhibitors with pancreatic cancer. In a joint letter to the New England Journal of Medicines, the agencies stated that "Both agencies agree that assertions concerning a causal association between incretin-based drugs and pancreatitis or pancreatic cancer, as expressed recently in the scientific literature and in the media, are inconsistent with the current data. The FDA and the EMA have not reached a final conclusion at this time regarding such a causal relationship. Although the totality of the data that have been reviewed provides reassurance, pancreatitis will continue to be considered a risk associated with these drugs until more data are available; both agencies continue to investigate this safety signal.
Lawsuits have been filed in which plantiffs who developed pancreatic cancer claim that DPP-IV inhibitors or incretins had a causative role in the development of their cancers.

# Further reading
- Herper, Matthew; Langreth, Robert (27 April 2006). "Diabetes Drugs to Watch". Forbes.com. Pharmaceuticals. Retrieved 26 April 2009..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}See pages of this article for Galvus aka LAF237 (Novartis) and Januvia aka MK-0431 (Merck)
- Nielsen, L (2005). "Incretin mimetics and DPP-IV inhibitors for the treatment of type 2 diabetes". Drug Discovery Today. 10 (10): 70310. doi:10.1016/S1359-6446(05)03460-4. PMID 15896683.Includes table describing an overview of type 2 diabetes drug therapies; 76 references.