What are the effects of Dipeptidyl Peptidase-4 (DPP-4) inhibitors?

From the Guidelines

DPP-4 inhibitors should be used as second-line therapy after metformin or in patients who cannot tolerate other medications, due to their modest A1C reductions and minimal side effects, as shown in the most recent study from 2024 1.

Key Points

• DPP-4 inhibitors are oral medications that block the enzyme dipeptidyl peptidase-4, helping to lower blood glucose levels.
• Common DPP-4 inhibitors include sitagliptin, saxagliptin, linagliptin, and alogliptin, typically taken once daily.
• Standard dosing varies by medication, with dose adjustments needed for patients with kidney impairment.
• DPP-4 inhibitors offer modest A1C reductions (0.5-0.8%) without causing weight gain or hypoglycemia when used alone.
• They are well-tolerated with minimal side effects, making them suitable for elderly patients or those at risk for hypoglycemia.

Considerations

• DPP-4 inhibitors are less potent than other diabetes medications like GLP-1 receptor agonists or SGLT2 inhibitors, which also offer cardiovascular and renal benefits.
• The most recent study from 2024 1 shows that SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality and MACE compared with usual care, while DPP-4 inhibitors do not.
• Another study from 2024 2 confirms that SGLT2 inhibitors and GLP1 agonists reduce severe hypoglycemia and serious adverse events compared with insulin or SU.

Recommendations

• Use DPP-4 inhibitors as second-line therapy after metformin or in patients who cannot tolerate other medications.
• Monitor patients for signs and symptoms of heart failure, as saxagliptin has been associated with increased risk of HF hospitalization 3.
• Adjust dosing according to renal function, as required for sitagliptin, saxagliptin, alogliptin, and vildagliptin 4.

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.

There have been postmarketing reports of acute pancreatitis, heart failure, hypersensitivity reactions, hepatic failure, hypoglycemia, arthralgia, and bullous pemphigoid in patients taking DPP-4 inhibitors.

DPP-4 Inhibitors are a class of medications that include alogliptin and saxagliptin. The main use of DPP-4 inhibitors is as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

• Key benefits: improve glycemic control
• Key risks: + acute pancreatitis + heart failure + hypersensitivity reactions + hepatic failure + hypoglycemia + arthralgia + bullous pemphigoid [5] [6]

From the Research

DPP-4 Inhibitors Overview

• DPP-4 inhibitors are a class of oral antidiabetic drugs that improve glycaemic control without causing weight gain or increasing hypoglycaemic risk in patients with type 2 diabetes mellitus (T2DM) 7.
• There are eight available DPP-4 inhibitors, including alogliptin, anagliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin, which have identical mechanisms of action and similar safety profiles in patients with T2DM 7.

Mechanism of Action and Efficacy

• DPP-4 inhibitors work by inhibiting the inactivation of glucagon-like peptide-1 (GLP-1), thereby increasing insulin secretion and reducing glucagon secretion 8.
• DPP-4 inhibitors have been shown to improve metabolic control in type 2 diabetes in monotherapy and in combination with metformin, sulphonylurea, and thiazolidinediones, with HbA(1c) reductions of approximately 0.6-1.1% in studies up to 52 weeks 8.
• Sitagliptin, a DPP-4 inhibitor, has been shown to enhance postprandial levels of active GLP-1, leading to a rise in insulin release and decrease in glucagon secretion from pancreatic alpha-cells 9.

Safety and Tolerability

• DPP-4 inhibitors are safe and tolerable with no increased risk of adverse events compared to placebo and have a low risk of hypoglycaemia 8.
• DPP-4 inhibitors are body weight-neutral, and significant hypoglycemia and weight gain have not been noted in studies 9, 10.
• The off-target inhibition of selective DPP-4 inhibitors is responsible for multiorgan toxicities such as immune dysfunction, impaired healing, and skin reactions 7.

Combination Therapy with Insulin

• The combination of DPP-4 inhibitors with insulin may be beneficial in patients with type 2 diabetes, as it can limit insulin dose and regimen complexity, and reduce the risk of hypoglycemia and weight gain 11.
• DPP-4 inhibitors may be of special value in decreasing glycemic excursions that are not properly addressed by basal insulin therapy and metformin use, even after optimizing titration of the basal insulin 11.