Dipeptidyl Peptidase 4 (DPP-4) Inhibitors

Reviewed by: HU Medical Review Board | Last reviewed: August 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

  • Headache
  • 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

  • Diet
  • Exercise
  • 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:
    • Vitamins
    • Supplements
    • Over-the-counter drugs

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