Long-term effects of DPP-4 inhibitors on mortality and morbidity are so far inconclusive, although adverse effects, including nasopharyngitis, headache, nausea, hypersensitivity and skin reactions, have been observed in clinical studies. Consistent with this FDA approval of Novartis' DPP-4 inhibitor vildagliptin (Galvus®) was delayed because of skin lesions with blistering observed in nonhuman primate toxicology studies; One year later, Novartis CEO Dan Vasella remained uncertain as to their ability to ever file to market the drug in the United States. Other possible adverse effects, including hypersensitivity reactions and pancreatitis, have been reported. These effects may relate to DPP-4's function in restricting the inflammatory actions of the chemokineCCL11/eotaxin, so that inhibiting DPP-4 might unleash the recruitment of inflammatory cells.
An in vitro study found that DPP-4 inhibitors, together with GLP-2, increased proliferation and migration of colon cancer cells, which might encourage cancer cells to metastasize,
Dr. Peter C. Butler, Chief of Endocrinology at UCLA and former editor of Diabetes, the flagship journal of the American Diabetes Association, studied the DPP-4 inhibitor "Januvia" and "found worrisome changes in the pancreases of the rats that could lead to pancreatic cancer". His follow-up studies now threaten the future of not only Januvia but all the drugs in its class (DPP-4 inhibitors). There are currently more than 100 lawsuits representing 575 plaintiffs around the country are claiming injury from the GLP-1 agonist, Byetta, according to the latest quarterly regulatory filing from Bristol-Myers. Forty-three suits claim that another DPP-4 inhibitor, Januvia, caused pancreatic cancer, according to Merck. Dr. Butler and colleagues found far more cases of pancreatitis and pancreatic cancer reported for the [DPP-4 inhibitor] drugs than for Avandia. In Dr. Butler’s study of human pancreases obtained from 34 organ donors who had died for reasons unrelated to pancreatic disease, seven of the donors happened to have taken Januvia and one had taken Byetta. the pancreases of those eight people tended to have more precancerous lesions than the organs of the diabetics who had not taken those drugs, or those of the nondiabetics. There was also one case of a neuroendocrine tumor, a type of pancreatic cancer. Also, the pancreases of the incretin drug users were heavier, with faster growth of certain cells. “There were strange growths” that “you’d never see in a normal human pancreas,” Dr. Alexandra Butler said. 
A 2013 study showed roughly a doubling of the risk of acute pancreatitis among users of the DPP-4 inhibitors. 
In March of 2013, the FDA issued a Drug Safety Communication announcing investigations into DDP-4 inhibitors due to findings by academic researchers that could lead to new warnings and possible removal from the market if the findings are confirmed.  A few weeks later, the European Medicines Agency launched a similar investigation into GLP-1 agonists and DPP-4 inhibitors that could lead to similar warnings, restrictions or removals from market. 
In August of 2013, a federal judiciary panel approved the consolidation of dozens of lawsuits against manufacturers of DPP-4 inhibitors before a judge in U.S. District Court in San Diego. Claims involving allegations of pancreatitis, pancreatic cancer and other side effects attributed to the use of Januvia, Janumet, Byetta and Victoza will continue to be eligible for review. The U.S. Judicial Panel on Multidistrict Litigation in its order described the common allegations: “Plaintiffs in all actions allege that the use of one or more of four anti-diabetic incretin based medications – Janumet (sitagliptin combined with metformin), Januvia (sitagliptin), Byetta (exenatide) and Victoza (liraglutide) – caused them or their decedent to develop pancreatic cancer,” the panel said. The order referenced the March 2013 FDA study announcement that included the drugs exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). 
Herper, Matthew; Langreth, Robert (27 April 2006). "Diabetes Drugs to Watch". Forbes.com. Pharmaceuticals. Retrieved 26 April 2009 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 Today10 (10): 703–10. doi:10.1016/S1359-6446(05)03460-4. PMID15896683. Includes table describing an overview of type 2 diabetes drug therapies; 76 references.
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^Joanne Bronson, Amelia Black, T. G. Murali Dhar, Bruce A. Ellsworth, and J. Robert Merritt. To Market, To Market - 2012. "Teneligliptin (Antidiabetic)". Annual Reports in Medicinal Chemistry48: 523–524.
^Goldstein, Jacob (January 17, 2008). "Novartis Diabetes Drug May Never Be Sold in U.S.". Wall Street Journal Health Blog. Wall Street Journal. Retrieved 2011-09-19. "“It’s on the cards, that we won’t refile, but it’s also on the cards that we will,” [Novartis CEO Dan Vasella] said, according to Dow Jones Newswires. “But what is certainly clear, is that refiling without new data makes no sense.""