DPP-4 inhibitors
Contents
Background
- 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
DPP-4 inhibitors inhibit the enzyme DPP-4, which is expressed on the surface of most cell types. DPP-4 deactivates other bioactive peptides, including incretins like glucagon-like peptide-1 (GLP-1). GLP-1 is secreted in the small intestines in response to nutrients, stimulating glucose-dependent insulin release from the pancreatic beta-cells, which then decrease blood sugar levels. Additionally, it decreases gastric emptying and inhibits postprandial glucagon release.
Adverse Effects
In controlled clinical studies of sitagliptin as monotherapy and combination therapy, the overall incidence of adverse reactions and the discontinuation of therapy in those taking sitagliptin was similar to that in those taking the placebo. The most commonly reported adverse reactions include nasopharyngitis, upper respiratory tract infection and headache.
Postmarketing surveillance found an association between those taking sitagliptin and development of acute pancreatitis, though confounding variables include risk factors such as diabetes, hypercholesterolemia, hypertriglyceridemia and obesity. Approximately 3 months after sitigliptin initiation, there were also reports of serious allergic reactions including anaphylactoid reactions, angioedema and exfoliate dermatologic reactions such as Stevens-Johnson syndrome.
Studies of other drugs in this class additionally report lymphopenia, cough, peripheral edema, transaminitis, and hypertension.
Patients taking DPP-4 inhibitors have also been found to develop joint pain, which often ceased within a month of discontinuation of the medication.
