What are Dipeptidyl Peptidase-4 Inhibitors (DPP4I) medications?

From the Guidelines

DPP4 inhibitors are a suitable treatment option for type 2 diabetes, offering a moderate glucose-lowering efficacy with a low risk of hypoglycemia, making them a viable choice for patients with mild-to-moderate hyperglycemia. According to the most recent evidence from 2021 1, DPP4 inhibitors have been shown to be well tolerated and effective for glycaemic control in the hospital setting, with a low risk of hypoglycaemia. The study found that sitagliptin plus basal insulin was as effective as basal–bolus insulin therapy in patients with type 2 diabetes with mild hyperglycaemia.

Key Characteristics of DPP4 Inhibitors

• They are oral medications that increase insulin secretion and reduce glucagon secretion in a glucose-dependent manner 1
• They have a neutral effect on weight and minimal risk of hypoglycemia when used as monotherapy 1
• They are suitable for elderly patients or those with renal impairment, though dose adjustments may be needed for some agents 1
• Common DPP4Is include sitagliptin (Januvia, 100mg daily), saxagliptin (Onglyza, 2.5-5mg daily), linagliptin (Tradjenta, 5mg daily), and alogliptin (Nesina, 25mg daily)

Clinical Use of DPP4 Inhibitors

• They are typically used as second-line therapy after metformin or as initial therapy in patients who cannot tolerate metformin
• They offer the convenience of once-daily oral dosing and do not cause significant gastrointestinal side effects or promote weight loss, unlike GLP-1 receptor agonists
• Linagliptin has been shown to result in a substantial reduction in the incidence of hypoglycaemia compared with basal–bolus therapy 1

Side Effects and Safety

• Side effects are generally mild and may include upper respiratory infections, headache, and rarely joint pain 1
• Rare but increased rates of pancreatitis and musculoskeletal side effects have been reported 1
• CVOTs have demonstrated the cardiovascular safety but no cardiovascular benefit of three DPP-4 inhibitors (saxagliptin, alogliptin, and sitagliptin) as well as imbalances regarding HF for saxagliptin and alogliptin 1

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. 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.

DPP4I medications are used to improve glycemic control in adults with type 2 diabetes mellitus.

• Saxagliptin and alogliptin are examples of DPP4I medications.
• They are indicated as an adjunct to diet and exercise.
• Not recommended for the treatment of type 1 diabetes or diabetic ketoacidosis 2, 3, 3.

From the Research

DPP4I Medications Overview

• DPP4I medications 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) 4.
• There are eight available DPP-4 inhibitors, including alogliptin, anagliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin, which are small molecules used orally with identical mechanism of action and similar safety profiles in patients with T2DM 4.

Mechanism of Action and Efficacy

• DPP-4 inhibitors work by inhibiting the activity of DPP-4, an enzyme that breaks down incretin hormones, thereby increasing the levels of these hormones and enhancing glucose-dependent insulin secretion 5, 6.
• DPP-4 inhibitors have been shown to improve metabolic control in type 2 diabetes in monotherapy and also in combination with metformin, sulphonylurea, and thiazolidinediones, with a reduction in HbA(1c) of approximately 0.6-1.1% in studies up to 52 weeks 6, 7.
• The addition of a DPP-4 inhibitor to basal insulin is an attractive option, as it lowers both postprandial and fasting plasma glucose concentrations without increasing the risk of hypoglycemia or weight gain 7.

Safety and Tolerability

• DPP-4 inhibitors are generally well-tolerated with a low risk of hypoglycaemia, a neutral effect on body weight, and once-daily dosing 4, 5, 8.
• The safety and efficacy of DPP4 inhibitors as monotherapy or in combination with other oral antidiabetic agents or basal insulin are well established, with a favourable therapeutic profile and low risk of adverse events 5, 7.
• However, there is a potential small increased risk of acute pancreatitis associated with DPP-4 inhibitors, and off-target adverse effects such as immune dysfunction, impaired healing, and skin reactions have been reported 4, 5.