From the Guidelines
DPP-4 inhibitors play a significant role in antidiabetic treatment by increasing the endogenous level of GLP-1, which enhances insulin secretion and inhibits glucagon secretion in a glucose-dependent manner 1.
Key Characteristics of DPP-4 Inhibitors
- Examples of DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin, linagliptin, and alogliptin 1.
- Glucose-lowering efficacy is moderate, with a reduction in HbA1c level by 0.4% to 0.9% in clinical trials 1.
- Neutral effect on weight and minimal risk of hypoglycemia when used as monotherapy, but increased risk of hypoglycemia when added to sulfonylurea therapy 1.
- Cardiovascular safety has been demonstrated in CVOTs, but no cardiovascular benefit has been shown for saxagliptin, alogliptin, and sitagliptin 1.
Important Considerations
- Renal function monitoring is essential, as DPP-4 inhibitors are primarily excreted by the kidneys, and dosage adjustments may be necessary for patients with renal dysfunction, except for linagliptin which has minimal renal excretion 1.
- Caution in patients with a history of pancreatitis or hypersensitivity reactions, as rare but increased rates of pancreatitis and musculoskeletal side effects have been reported 1.
- Individualized treatment and regular monitoring for efficacy and potential side effects are crucial when using DPP-4 inhibitors.
From the FDA Drug Label
Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes mellitus, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved Saxagliptin is a competitive DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients 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.
The role of DPP-4 inhibitors in antidiabetic treatment is to:
- Slow the inactivation of incretin hormones such as GLP-1 and GIP
- Increase the bloodstream concentrations of these hormones
- Reduce fasting and postprandial glucose concentrations in a glucose-dependent manner
- Improve glycemic control in adults with type 2 diabetes mellitus, as an adjunct to diet and exercise 2, 2, 2. Key benefits of DPP-4 inhibitors include:
- Glucose-dependent insulin secretion: reducing the risk of hypoglycemia
- Reduced glucagon secretion: decreasing hepatic glucose production
- Improved glycemic control: as an adjunct to diet and exercise in adults with type 2 diabetes mellitus.
From the Research
Role of DPP-4 Inhibitors in Antidiabetic Treatment
- DPP-4 inhibitors are a class of oral anti-hyperglycemic agents that inhibit the enzyme DPP-4, thus augmenting the biological activity of the "incretin" hormones (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) and restoring many of the pathophysiological problems of diabetes 3.
- They have a favorable therapeutic profile and are safe and effective in the majority of patients with type 2 diabetes mellitus, with a low risk of hypoglycemia and a weight-neutral effect 4, 5, 6.
- DPP-4 inhibitors are often used as second-line therapy after metformin, and are available as fixed-dose combination pills with metformin or with SGLT-2 inhibitors 7.
Mechanism of Action
- DPP-4 inhibitors act by increasing endogenous GLP-1 and GIP concentrations, which stimulates insulin secretion and inhibits glucagon secretion in a glucose-dependent manner 6.
- This mechanism of action results in a low risk of hypoglycemia and a weight-neutral effect, making DPP-4 inhibitors a desirable treatment option for patients with type 2 diabetes 4, 5.
Efficacy and Safety
- DPP-4 inhibitors have been shown to be effective in improving glycemic control and have a favorable safety profile, with a low risk of hypoglycemia and no significant effect on weight 4, 5, 6.
- However, some DPP-4 inhibitors may have a small increased risk of acute pancreatitis, and individual agents may have differing chemistries and/or pharmacokinetic profiles that can affect their therapeutic use and potential off-target adverse effects 4.