What are DPP-4 (Dipeptidyl Peptidase-4) inhibitors for diabetes?

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Last updated: May 28, 2025View editorial policy

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From the Guidelines

DPP-4 inhibitors are a suitable treatment option for type 2 diabetes, particularly for patients who cannot tolerate metformin or require second-line therapy, due to their moderate glucose-lowering efficacy and minimal risk of hypoglycemia when used alone 1.

Key Characteristics of DPP-4 Inhibitors

  • They work by blocking the enzyme that breaks down incretin hormones, increasing insulin production and reducing glucose production from the liver.
  • Common DPP-4 inhibitors include sitagliptin, saxagliptin, linagliptin, and alogliptin, with typical daily doses of 100mg, 5mg, 5mg, and 25mg, respectively.
  • These medications are generally well-tolerated, with minimal risk of hypoglycemia when used alone and no significant effect on weight gain.

Clinical Use and Considerations

  • DPP-4 inhibitors are often prescribed as second-line therapy after metformin or for patients who cannot tolerate metformin.
  • They are particularly useful for elderly patients or those with kidney disease, although dose adjustments may be necessary for some DPP-4 inhibitors in cases of kidney impairment 1.
  • Side effects are generally mild and may include upper respiratory infections, headache, and rarely joint pain.

Recent Evidence and Recommendations

  • Recent studies have demonstrated the effectiveness of DPP-4 inhibitors in achieving glycaemic control with a low risk of hypoglycaemia in patients with mild-to-moderate hyperglycaemia 1.
  • The 2018 American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) consensus report recommends considering DPP-4 inhibitors as part of a patient-centered approach to managing type 2 diabetes 1.
  • However, it is essential to consider the potential increased risk of heart failure associated with certain DPP-4 inhibitors, such as saxagliptin and alogliptin, particularly in patients with preexisting heart failure or renal impairment 1.

From the FDA Drug Label

Alogliptin tablets are a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. TRADJENTA is a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

DPP-4 medications for diabetes are used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The medications include:

  • Alogliptin 2
  • Linagliptin 3
  • Saxagliptin 4 These medications are not recommended for the treatment of type 1 diabetes or diabetic ketoacidosis.

From the Research

DPP4 Inhibitors for Diabetes Treatment

  • DPP4 inhibitors are a class of oral antidiabetic agents that enhance the body's ability to regulate blood glucose by increasing the active levels of incretins, such as glucagon-like peptide 1 (GLP-1) 5, 6, 7, 8, 9.
  • They work by stimulating glucose-dependent insulin secretion and inhibiting glucagon production, resulting in improved glycemic control 5, 6, 7, 8, 9.

Efficacy and Safety

  • DPP4 inhibitors have been shown to be effective in reducing hemoglobin A1c (HbA1c) levels by approximately 0.6-1.1% as monotherapy or in combination with other oral antidiabetic agents or basal insulin 5, 6, 7, 8, 9.
  • They have a low risk of hypoglycemia and are body weight-neutral, making them a suitable treatment option for patients with type 2 diabetes 5, 6, 7, 8, 9.
  • The safety and efficacy of DPP4 inhibitors have been established in various patient populations, including the elderly and those with renal impairment 5, 7.

Clinical Applications

  • DPP4 inhibitors can be used as monotherapy or in combination with other antidiabetic agents, such as metformin, sulphonylurea, and thiazolidinediones 5, 6, 7, 8, 9.
  • They may also be used in combination with basal insulin, providing an alternative to basal-bolus insulin regimens in hospitalized patients with type 2 diabetes 5.
  • Sitagliptin, a DPP4 inhibitor, has been shown to be effective and well-tolerated in various treatment regimens, including as initial therapy and as add-on therapy for patients with type 2 diabetes 9.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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