DPP-4 inhibitors

Focus on safety

Sri Harsha Tella, Marc S. Rendell

Research output: Contribution to journalReview article

21 Citations (Scopus)

Abstract

Introduction: 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.Areas covered: 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.Expert opinion: 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.

Original languageEnglish
Pages (from-to)127-140
Number of pages14
JournalExpert Opinion on Drug Safety
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

glimepiride
Safety
Glucagon-Like Peptides
Dipeptidyl-Peptidase IV Inhibitors
Incretins
Gastric Emptying
Expert Testimony
Enzyme Inhibitors
Glucagon
Pancreatic Neoplasms
Drug Interactions
Hypoglycemia
PubMed
Pancreatitis
Cytochrome P-450 Enzyme System
Uncertainty
Heart Diseases
Heart Failure
Clinical Trials
Hormones

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)
  • Medicine(all)

Cite this

DPP-4 inhibitors : Focus on safety. / Tella, Sri Harsha; Rendell, Marc S.

In: Expert Opinion on Drug Safety, Vol. 14, No. 1, 01.01.2015, p. 127-140.

Research output: Contribution to journalReview article

Tella, Sri Harsha ; Rendell, Marc S. / DPP-4 inhibitors : Focus on safety. In: Expert Opinion on Drug Safety. 2015 ; Vol. 14, No. 1. pp. 127-140.
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