DPP-4 inhibitors


  • Dipeptidyl Peptidase-4 Inhibitors (gliptans) are a class of oral hypoglycemics that block DPP-4. This leads to an increase in the activity of incretins, which inhibit glucagon release, which in turn increase insulin secretion and slow gastric emptying, ultimately decreasing blood glucose levels. These drugs are commonly used in the treatment of type 2 diabetes.
  • Generally used as second or third line treatment for type 2 diabetes mellitus. They may be used as monotherapy or combined therapy.

FDA Approved DPP-4 Inhibitors

Brand Name Active Ingredient(s)
Januvia sitagliptin
Janumet sitagliptin, metformin
Janumet XR sitagliptin, metformin ER
Onglyza saxagliptin
Kombiglyze XR saxagliptin, metformin ER
Tradjenta linagliptin
Glyxambi linagliptin, empagliflozin
Jentadueto linagiptin, metformin
Nesina alogliptin
Kazano alogliptin, metformin
Oseni alogliptin, pioglitazone

Mechanism of Action

  • Inhibit DPP-4, an enzyme expressed on surface of most cell types
  • DPP-4 deacctivates other bioactive peptides, including incretins such as glucagon-like peptide-1 (GLP-1).
  • GLP-1 is secreted in response to nutrients, stimulating glucose-dependent insulin release from pancreatic beta-cells, which in turn decreases blood sugar levels.
  • Also decreases gastric emptying and inhibits postprandial glucagon release

Adverse Effects

  • In controlled studies of sitagliptin (as monotherapy and combination therapy), overall incidence of adverse reactions/discontinuation similar to placebo
  • Most commonly reported adverse reactions include nasopharyngitis, URI, HA
  • Postmarketing surveillance found association with sitagliptin and development of acute pancreatitis
    • Confounding variables such as diabetes, hypercholesterolemia, hypertriglyceridemia, obesity
  • Also postmarketing reports of serious allergic reactions (including anaphylactoid reactions, angioedema, SJS)
  • Studies of other drugs in this class additionally report lymphopenia, cough, peripheral edema, transaminitis, and hypertension.
  • Other side effects reported in patients taking this class of medication include joint pain

See Also