Pharmacokinetics, safety, and efficacy of DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus and renal or hepatic impairment. A systematic review of the literature

Endocrine. 2014 Aug;46(3):406-19. doi: 10.1007/s12020-014-0179-0. Epub 2014 Feb 8.


Renal or hepatic impairment, often encountered in patients with type 2 diabetes, influences the pharmacokinetics and bioavailability of antihyperglycemic agents. An emerging concern is whether pharmacotherapy with incretin-based agents, the most recent drug classes to be introduced for type 2 diabetes, can be safely used in patients with renal insufficiency or hepatic damage. This literature review examines the results of studies on these novel drug classes, with a view to provide the practitioner with a balanced, evidence-based position when considering incretin-based therapies in patients with type 2 diabetes and impaired kidney or liver function. All currently available dipeptidyl peptidase-4 (DPP-4) inhibitors appear to be appropriate pharmacotherapeutic choices in patients with declining renal function, with linagliptin affording the added advantage of not requiring dose adjustment or periodic monitoring of drug-related kidney function. In contrast, caution is warranted with the use of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with moderate or severe renal impairment. The slightly wider evidence base for liraglutide than for exenatide or lixisenatide is not sufficient to support its use in severe renal impairment. What little evidence there is for incretin-based therapies in hepatic impairment has come from a few past hoc analysis of clinical trials, with most precautions and warnings reflecting the paucity of knowledge about incretin efficacy or safety in this condition.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use*
  • Kidney / drug effects
  • Kidney / physiopathology*
  • Liver / drug effects
  • Liver / physiopathology*
  • Receptors, Glucagon / antagonists & inhibitors*
  • Treatment Outcome


  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Receptors, Glucagon