DPP-4 Inhibitors for Type 2 Diabetes
The commonly used DPP-4 inhibitors for type 2 diabetes treatment include sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin. 1, 2
Mechanism of Action
- DPP-4 inhibitors work by increasing endogenous levels of GLP-1 by preventing its deactivation, which enhances insulin secretion and inhibits glucagon secretion in a glucose-dependent manner 3
- These oral medications have moderate glucose-lowering efficacy, typically reducing HbA1c by approximately 0.4% to 0.9% 3, 4
- They specifically target postprandial glucose control by reducing postprandial glucagon secretion 3, 5
Available DPP-4 Inhibitors
- Sitagliptin: One of the first approved and most widely used DPP-4 inhibitors 2, 6
- Vildagliptin: Well-established DPP-4 inhibitor with proven efficacy 2, 4
- Saxagliptin: Metabolized by CYP3A4/5 to an active metabolite; requires dose adjustment with strong CYP3A4/5 inhibitors 5, 7
- Linagliptin: Unique among DPP-4 inhibitors as it has minimal renal excretion and doesn't require dose adjustment in renal impairment 1, 8
- Alogliptin: Another commonly used DPP-4 inhibitor 2, 8
- Other less common DPP-4 inhibitors include anagliptin, gemigliptin, and teneligliptin 2
Clinical Use
- DPP-4 inhibitors can be used as monotherapy or in combination with other antidiabetic medications such as metformin, thiazolidinediones, sulfonylureas, or insulin 1, 7
- They have minimal risk of hypoglycemia when used as monotherapy, making them suitable for various patient populations 1
- When added to sulfonylurea therapy, the risk for hypoglycemia is increased by approximately 50% compared to sulfonylurea therapy alone 1
Safety Considerations
- Most DPP-4 inhibitors require dose adjustment based on renal function, with linagliptin being the exception as it has minimal renal excretion 1, 3
- Cardiovascular safety trials have demonstrated cardiovascular safety but no cardiovascular benefit for sitagliptin, saxagliptin, and alogliptin 1
- Saxagliptin and alogliptin have been associated with imbalances regarding heart failure risk 1
- Rare but increased rates of pancreatitis and musculoskeletal side effects have been reported with DPP-4 inhibitors 1, 3
Pharmacokinetic Differences
- Most DPP-4 inhibitors have minimal drug-drug interactions due to limited binding to plasma proteins 7
- Saxagliptin is metabolized by CYP3A4/5 and may have significant interactions with strong inhibitors (ketoconazole, diltiazem) or inducers (rifampicin) of these enzymes 5, 7
- DPP-4 inhibitors are generally weight-neutral, unlike some other diabetes medications 1, 4