Dipeptidyl Peptidase 4 (DPP-4) Inhibitors
Reviewed by: HU Medical Review Board | Last reviewed: August 2023 | Last updated: September 2023
Dipeptidyl peptidase 4 (DPP-4) inhibitors are drugs used to treat type 2 diabetes (T2D). They help lower blood sugar (glucose) by increasing the levels of certain hormones. Four DPP-4 inhibitors are currently approved to treat people with T2D.
DPP-4 inhibitors are not the first treatment option for T2D. If diet, exercise, and other drugs are not effective, your doctor may suggest trying DPP-4 inhibitors. Talk to your doctor about the specific benefits and risks of DPP-4 inhibitors.
How do DPP-4 inhibitors work?
DPP-4 inhibitors work by altering levels of certain hormones called "incretin" hormones. These are hormones that help reduce blood sugar levels after eating. Two incretin hormones are glucagon-like peptide-1 and gastric inhibitory peptide.1
Your gut releases these hormones right after you eat. Your pancreas then releases insulin. This process removes glucose from the blood. The DPP-4 enzyme in your body breaks down these hormones.1,2
Blocking DPP-4 increases levels of incretin hormones. This helps lower blood sugar levels for people with T2D.1,2
The US Food and Drug Administration (FDA) has approved 4 DPP-4 inhibitors to treat diabetes:2
- Nesina® (alogliptin)
- Januvia® (sitagliptin)
- Onglyza® (saxagliptin)
- Tradjenta® (linagliptin)
Another DPP-4 inhibitor, vildagliptin, is only available outside the United States. The choice between DPP-4 inhibitors depends on a number of factors, including:2
- Personal preference
- Insurance coverage
- Other medical conditions you may have, such as chronic kidney disease
What are the possible side effects?
Side effects can vary depending on the specific DPP-4 inhibitor you are taking. But DPP-4 inhibitors usually do not cause serious side effects. Two side effects with a very low risk of happening when you take DPP-4 inhibitors are changes in your weight and low blood sugar (hypoglycemia). The risks increase when you use DPP-4 inhibitors at the same time as sulfonylureas.1,2
The risk for side effects varies for each DPP-4-inhibiting drug. The most common side effects of DPP-4 inhibitors include:1,2
- Symptoms of a common cold (nasopharyngitis)
- Other infections of the upper respiratory tract
More serious side effects of DPP-4 inhibitors are possible, but very rare. These include:1,2
- Allergic reactions (such as anaphylaxis and angioedema)
- Inflammation of the pancreas (pancreatitis)
- Liver or kidney problems
- Inflammatory bowel disease
- Joint pain
- Skin reactions
These are not all the possible side effects of DPP-4 inhibitors. Talk to your doctor about what to expect when taking DPP-4 inhibitors. You also should call your doctor if you have any changes that concern you when taking DPP-4 inhibitors, including changes in your symptoms.
Other things to know
DPP-4 inhibitors are not the first choice of therapy for people with T2D. Most people will start with:1,2
- Metformin or other drugs
If these treatments do not work, your doctor may then suggest using DPP-4 inhibitors.1,2
DPP-4 inhibitors are usually taken by mouth once a day, with or without food. Take DPP-4 inhibitors exactly as your doctor tells you. Your doctor may perform kidney function and other tests before and during treatment. Before starting treatment, tell your doctor if:1,2
- You have any other medical conditions
- You have any allergies
- You take any other drugs, including:
- Over-the-counter drugs