From the Guidelines
Januvia (sitagliptin) works by inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4), which normally breaks down incretin hormones like glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), as stated in the most recent study 1.
Mechanism of Action
By blocking DPP-4, Januvia increases the levels of these incretin hormones in the bloodstream. These hormones stimulate insulin release from pancreatic beta cells when blood glucose is elevated, while simultaneously suppressing glucagon secretion from pancreatic alpha cells. This dual action helps lower blood glucose levels in a glucose-dependent manner, meaning it works more effectively when blood sugar is high and less when blood sugar is normal, which reduces the risk of hypoglycemia.
Key Characteristics
- Januvia is typically prescribed at a dose of 100 mg once daily for patients with type 2 diabetes who have normal kidney function, with lower doses (50 mg or 25 mg daily) for those with moderate to severe renal impairment, as noted in 1 and 1.
- Unlike some other diabetes medications, Januvia is weight-neutral and does not cause hypoglycemia when used alone, making it a valuable option for managing type 2 diabetes, particularly in combination with other antidiabetic medications like metformin.
- The use of DPP-4 inhibitors, including sitagliptin, has been shown to have a neutral effect on cardiovascular disease, as reported in 1 and 1.
Clinical Considerations
- Dose adjustment is required based on kidney function for sitagliptin, as stated in 1.
- Januvia has been shown to have a moderate glucose-lowering efficacy and is well-tolerated, with a minimal risk of hypoglycemia when used as monotherapy, as noted in 1.
- Rare but increased rates of pancreatitis and musculoskeletal side effects have been reported with the use of DPP-4 inhibitors, including sitagliptin, as mentioned in 1 and 1.
From the Research
Mechanism of Action of Sitagliptin
- Sitagliptin is a selective antagonist of dipeptidylpeptidase-4 (DPP-4), an enzyme that degrades glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) 2, 3, 4, 5.
- By inhibiting DPP-4, sitagliptin increases the levels of active GLP-1 and GIP, which in turn stimulate insulin secretion and inhibit glucagon secretion in a glucose-affected manner 2, 3, 4, 5.
- The increased levels of GLP-1 and GIP enhance the postprandial insulin response, leading to improved glycemic control 2, 3, 4, 5.
Effects on Glycemic Control
- Sitagliptin improves glycemic control by reducing hemoglobin A1c (HbA1c) levels, postprandial glucose excursion, and fasting plasma glucose 2, 3, 6, 5.
- It has been shown to be effective as monotherapy or in combination with other oral antidiabetic agents, including metformin, sulfonylureas, and thiazolidinediones 2, 3, 6, 5.