Comparative review of dipeptidyl peptidase-4 inhibitors and sulphonylureas

Diabetes Obes Metab. 2016 Apr;18(4):333-47. doi: 10.1111/dom.12610. Epub 2016 Jan 8.


Type 2 diabetes (T2DM) is a progressive disease, and pharmacotherapy with a single agent does not generally provide durable glycaemic control over the long term. Sulphonylurea (SU) drugs have a history stretching back over 60 years, and have traditionally been the mainstay choice as second-line agents to be added to metformin once glycaemic control with metformin monotherapy deteriorates; however, they are associated with undesirable side effects, including increased hypoglycaemia risk and weight gain. Dipeptidyl peptidase (DPP)-4 inhibitors are, by comparison, more recent, with the first compound being launched in 2006, but the class now globally encompasses at least 11 different compounds. DPP-4 inhibitors improve glycaemic control with similar efficacy to SUs, but do not usually provoke hypoglycaemia or weight gain, are relatively free from adverse side effects, and have recently been shown not to increase cardiovascular risk in large prospective safety trials. Because of these factors, DPP-4 inhibitors have become an established therapy for T2DM and are increasingly being positioned earlier in treatment algorithms. The present article reviews these two classes of oral antidiabetic drugs (DPP-4 inhibitors and SUs), highlighting differences and similarities between members of the same class, as well as discussing the potential advantages and disadvantages of the two drug classes. While both classes have their merits, the choice of which to use depends on the characteristics of each individual patient; however, for the majority of patients, DPP-4 inhibitors are now the preferred choice.

Keywords: GLP-1; alogliptin; anagliptin; antidiabetic drug; diabetes mellitus; evogliptin; gemigliptin; glibenclamide; gliclazide; glimepiride; glipizide; glyburide; glycaemic control; incretin; linagliptin; omarigliptin; saxagliptin; sitagliptin; teneligliptin; trelagliptin; vildagliptin.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Administration, Oral
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Angiopathies / epidemiology
  • Diabetic Angiopathies / prevention & control
  • Diabetic Cardiomyopathies / epidemiology
  • Diabetic Cardiomyopathies / prevention & control
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glycated Hemoglobin / analysis
  • Humans
  • Hyperglycemia / prevention & control*
  • Hypoglycemia / chemically induced
  • Hypoglycemia / epidemiology
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use
  • Risk
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / adverse effects
  • Sulfonylurea Compounds / pharmacokinetics
  • Sulfonylurea Compounds / therapeutic use
  • Weight Gain / drug effects


  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • hemoglobin A1c protein, human