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Dipeptidyl Peptidase 4 (DPP-4) Inhibitors

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By Editorial Team

2 min read

Reviewed by: HU Medical Review Board | Last reviewed: August 2024 | Last updated: August 2024

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

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Blocking DPP-4 increases levels of incretin hormones. This helps lower blood sugar levels for people with T2D.1,2

Examples

The US Food and Drug Administration (FDA) has approved 4 DPP-4 inhibitors to treat diabetes:2

  • Januvia®, Zituvio® (sitagliptin)
  • Onglyza® (saxagliptin)
  • Tradjenta® (linagliptin)

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. 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
Treatment results and side effects can vary from person to person. This treatment information is not meant to replace professional medical advice. Talk to your doctor about what to expect before starting and while taking any treatment.