title: DPP-4 inhibitors: focus on safety.
abstract: BACKGROUND
  Dipeptidyl peptidase inhibitors (DPP-4-i) are highly selective inhibitors of the enzyme DPP-4. They act by increasing levels of incretin hormones, which have potent effects on insulin and glucagon release, gastric emptying, and satiety. Our goal is to review the safety issues related to DPP-4-i.
  
  
  METHODS
  This review is based upon a PubMed search of the literature using keywords alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin, DPP-4-i, glucagon-like polypeptide-1 agonists, as well as extensive personal clinical trial experience with each of these agents. The current DPP-4-i have very different chemical structures. Saxagliptin has significant cytochrome P450 metabolism and carries a risk of drug interactions. Linagliptin has primarily entero-hepatic excretion, a benefit in renally impaired patients. A concern arose related to congestive heart failure in the SAVOR TIMI trial of saxagliptin. Several major cardiac studies are underway, with two concluded. Despite lingering uncertainty related to pancreatitis and pancreatic cancer, large randomized trials have not shown an increased risk with DPP-4-i treatment. Cutaneous adverse effects occur with a low frequency with some of these agents.
  
  
  CONCLUSIONS
  DPP-4-i are an additional choice in the group of anti-hyperglycemics. Their principal advantage is a low incidence of hypoglycemia, making these agents desirable in patients such as the elderly and those with cardiac disease. Several large trials have hinted at less cardiac risk with DPP-4-i than with sulfonylureas. The CAROLINA Trial comparing linagliptin and glimepiride may provide a conclusive answer to this question.
authors.affiliation: Creighton Diabetes Center , 601 North 30th Street, Omaha, NE 68131 , USA.
authors.forename: Sri Harsha
authors.initials: SH
authors.lastname: Tella
authors.forename: Marc S
authors.initials: MS
authors.lastname: Rendell
mesh_terms: D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D007107:Immune System / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D015394:Molecular Structure; D010179:Pancreas / Q000187:drug effects; D012867:Skin / Q000187:drug effects
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents
keywords: alogliptin; dipeptidyl peptidase -4 inhibitors; glucagon-like polypeptide-1; linagliptin; saxagliptin; sitagliptin; vildagliptin