DPP-4 inhibitors: Uses, common brands, and safety information

Dipeptidyl peptidase-4 (DPP-4) inhibitors are used to manage blood sugar in people with Type 2 diabetes. Common DPP-4 inhibitors include Nesina (alogliptin), Tradjenta (linagliptin), saxagliptin, and Januvia (sitagliptin). DPP-4 inhibitors can be used on their own, or combined with other diabetes medications, such as metformin.

Here, we’ll take a detailed look at DPP-4 inhibitors, including how they work, who should use them, side effects, interactions, and more.

What are DPP-4 inhibitors?

DPP-4 inhibitors are a class of prescription medications that are FDA-approved for people with Type 2 diabetes. They work by increasing the body’s release of insulin, which helps lower blood sugar. They are meant to be used in combination with diet and exercise to manage and control blood sugar. Sometimes DPP-4 inhibitors are combined with other diabetes medications, and other times they are used on their own.

How do DPP-4 inhibitors work?

DPP-4 inhibitors work by increasing your body’s ability to produce insulin, which is a hormone that helps regulate your blood sugar, explains Sean Ormond, MD, dual board-certified in anesthesiology and interventional pain management physician at Atlas Pain Specialists. Dr. Ormond frequently sees patients with complex health issues, including diabetes.

The main way DPP-4 inhibitors help regulate blood is by slowing down an enzyme called DPP-4 that normally breaks down hormones including GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide), which help your body make insulin after you eat, Dr. Ormond describes. “By blocking this enzyme, the medication lets those hormones stick around longer, so your body releases more insulin to lower blood sugar right after meals.” Taking a DPP-4 inhibitor is like giving your body a boost to help manage blood sugar better, he says.

Although DPP-4 inhibitors are a newer class of diabetes medication, they are known to be effective in helping people lower their blood glucose and hemoglobin A1c (HbA1c) levels. According to Frontiers in Endocrinology, patients with diabetes who take DPP-4 inhibitors can potentially lower their A1c by 0.5-1%.

Other DPP-4 inhibitors

There are four DPP-4 inhibitors approved by the FDA: sitagliptin, saxagliptin, linagliptin, and alogliptin.

What are DPP-4 inhibitors used for?

DPP-4 inhibitors are meant for people with Type 2 diabetes only. They may be used alone or in combination with other antidiabetic agents, such as metformin, as part of a comprehensive plan for managing diabetes, says Erika Gray, PharmD, founder and chief medical officer at MyToolBox Genomics.

“It is important to note that this class of medication should not be used for or is for Type 1 diabetes, as DPP-4 inhibitors rely on the body being able to make some insulin in response to rising blood sugar,” Dr. Gray emphasizes. “Since those with Type 1 diabetes have little to no insulin-producing beta cells in their pancreas, DPP-4 inhibitors cannot effectively work to improve glycemic control.” 

According to Dr. Gray, some benefits of DPP-4 inhibitors include:

• Allows insulin to be released over a longer period of time

• Improved glucose control after eating

• Doesn’t increase hypoglycemic (low blood sugar) risk

• Doesn’t increase body weight

• Generally safe and low risk

Types of DPP-4 inhibitors

There are four DPP-4 inhibitors (and combination drugs that use DPP-4 inhibitors). They all work in the same way, inhibiting the production of the enzyme DPP-4, which helps raise insulin levels in the body and regulate blood sugar.

Here’s what to know about each DPP-4 inhibitor:

Sitagliptin 

Sold under the brand name Januvia, taken once daily and prescribed in 25, 50, or 100 mg doses.

Saxagliptin 

Previously sold under the brand name Onglyza, this drug is now only available as a generic. It is taken once daily and prescribed in 2.5 or 5 mg doses.

Linagliptin 

Sold under the brand name Tradjenta, taken once daily and prescribed in 5 mg doses.

Alogliptin 

Sold under the brand name Nesina, taken once daily and typically prescribed in 25 mg doses.

When these medications are combined with metformin, they are usually taken twice daily.

Who can take DPP-4 inhibitors?

Overall, DPP-4 inhibitors can be taken by most adults with Type 2 diabetes. “Most adults with Type 2 diabetes can take them safely,” says Dr. Ormond. Here’s what to know.

Adults

Adults—both men and women—can take DPP-4 inhibitors, as long as they have Type 2 diabetes. “They’re mainly used to help people with Type 2 diabetes control their blood sugar when diet and exercise alone aren’t enough,” says Dr. Ormond. “They aren’t used for other conditions or for Type 1 diabetes.”

Older adults

Most sources consider DPP-4 inhibitors to be mostly safe for older adults with Type 2 diabetes. They present a low risk for hypoglycemia (low blood sugar) in older adults. However, dosing for DPP-4 inhibitors may need to be adjusted for older adults

Who should not take DPP-4 inhibitors?

There are certain individuals who should not take DPP-4 inhibitors.

Children

As of now, DPP-4 inhibitors are not approved for use in children, so children should not take them.

Pregnant and breastfeeding women

We lack clinical evidence on the safety of DPP-4 inhibitors in both pregnant and breastfeeding women. “They are not indicated in pregnancy or breast-feeding,” says Betul Hatipoglu, MD, a professor of medicine at Case Western Reserve University. “We don’t know how safe they might be.”

People with certain medical conditions

DPP-4 inhibitors are safe for most people. However, people with the following medical conditions should not take DPP-4 inhibitors, according to Dr. Gray:

• People with a history of pancreatitis

• People with Type 1 diabetes

• People with hypersensitivities to DPP-4 inhibitors

• People in diabetic ketoacidosis

People with liver issues or kidney issues should exercise caution when taking DPP-4 inhibitors, according to Dr. Hatipoglu.

Are DPP-4 inhibitors safe?

Are DPP-4 inhibitors safe overall? “In general, they are safe medications,” Dr. Hatipoglu affirms. Here, we’ll take a thorough look at the safety profile of DPP-4 inhibitors.

Side effects

Many people don’t experience significant side effects while taking DPP-4 inhibitors. “They cause flu-like symptoms in some individuals,” says Dr. Hatipoglu. “They can cause skin rash in others.”

These are some common side effects of DPP-4 inhibitors:

• Low blood sugar (hypoglycemia), especially when used in combination with insulin or certain diabetes medicines

• Cold symptoms

• Respiratory infections

• Headaches

• Nausea

• Diarrhea

• Stomachaches

• Urinary tract infections (UTIs)

• Swelling in your legs, feet, and ankles (peripheral edema)

Recalls

There are no recent or current recalls on any DPP-4 inhibitors. You can search the FDA’s database to find updated recalls. 

Restrictions

You shouldn’t take DPP-4 inhibitors if:

• You are under the age of 18

• You have Type 1 diabetes

• You are in diabetic ketoacidosis

• You have a hypersensitivity to any DPP-4 inhibitor

• You are pregnant or breastfeeding

• You have a history of pancreatitis

Are DPP-4 inhibitors controlled substances?

No, DPP-4 inhibitors are not controlled substances.

How much do DPP-4 inhibitors cost?

The cost of DPP-4 inhibitors varies based on which medication you are buying, whether your health insurance company will cover it, and whether you are using coupons to help cover cost. The average cost of DPP-4 inhibitors if you are paying full price ranges from $1200 to $1600 per year.

Remember, DPP-4 inhibitors can be used on their own or in combination with other diabetes drugs like metformin or insulin. Consider reaching out to your healthcare provider to discuss the role that DPP-4 inhibitors can play in your diabetes management plan.

Sources

• Information on dipeptidyl peptidase-4 (DPP-4) inhibitors, U.S. Food and Drug Administration (2016)

• Clinical use of DPP-4 inhibitors, Frontiers in Endocrinology (2019)

• Dipeptidyl peptidase IV (DPP IV) inhibitors, StatPearls (2023)

• The Johns Hopkins Guide to Diabetes, DPP-IV inhibitors (2024)

• Antidiabetic medications in older adults, Arkansas Geriatric Education Collaborative (2017)

• DPP-IV inhibitors, Johns Hopkins Medicine (2018)

• Recalls, market withdrawals, & safety alerts, U.S. Food and Drug Administration (2025)

• Out-of-pocket costs for new guideline-directed antidiabetes drugs under Medicare part D, NEJM Journal Watch (2020)