From the Guidelines
Gliptins should not be used as a first-line add-on therapy to metformin for type 2 diabetes, as recommended by the American College of Physicians in 2024 1. When considering the use of gliptins, also known as dipeptidyl peptidase-4 (DPP-4) inhibitors, for type 2 diabetes, it is essential to prioritize the most recent and highest quality evidence. The American College of Physicians (ACP) recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence) 1.
Instead, the ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence) 1. Some key points to consider when using gliptins include:
- They work by preventing the breakdown of incretin hormones (GLP-1 and GIP), which helps increase insulin secretion and decrease glucagon release in a glucose-dependent manner.
- Gliptins are also appropriate for elderly patients or those with renal impairment (with dose adjustments for most gliptins except linagliptin).
- They have minimal drug interactions and can be safely combined with other diabetes medications.
- However, they should be used cautiously in patients with a history of pancreatitis, and they provide modest HbA1c reductions of approximately 0.5-0.8%.
- Side effects are generally mild and may include upper respiratory infections, headache, and rarely joint pain.
From the FDA Drug Label
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. Gliptins, such as saxagliptin, are used to improve glycemic control in adults with type 2 diabetes mellitus.
- They are used as an adjunct to diet and exercise.
- The use of gliptins is not recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis 2.
From the Research
Indications for Gliptins
Gliptins, also known as dipeptidyl peptidase-4 (DPP-4) inhibitors, are a class of oral hypoglycemic agents used in the treatment of type 2 diabetes. The following are indications for gliptins:
- As monotherapy in patients with type 2 diabetes who are not adequately controlled with diet and exercise alone 3, 4, 5
- In combination with metformin in patients with type 2 diabetes who are not adequately controlled with metformin alone 4, 5, 6
- In combination with sulfonylureas and thiazolidinediones in patients with type 2 diabetes who are not adequately controlled with these agents alone 5
- In combination with insulin in patients with type 2 diabetes who are not adequately controlled with insulin alone 5
Patient Populations
Gliptins can be used in various patient populations, including:
- Obese patients with type 2 diabetes 3
- Elderly patients with type 2 diabetes 3
- Patients with type 2 diabetes and established cardiovascular disease 3
- Patients with type 2 diabetes and renal impairment 3
- Chinese patients with type 2 diabetes inadequately controlled with dual combination of traditional oral hypoglycemic agents 7
Efficacy and Safety
Gliptins have been shown to be effective in improving glycemic control in patients with type 2 diabetes, with a low risk of hypoglycemia and no significant effect on body weight 3, 4, 5, 7, 6. They are generally well tolerated, with most adverse events being mild to moderate in intensity 3. However, there is ongoing discussion about the potential increased risk of pancreatitis and pancreatic cancer with incretin-based therapies, including gliptins, although no causal link has been established to date 3.