From the Guidelines
Linagliptin's mechanism of action involves inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4), increasing the half-life and concentration of incretin hormones like GLP-1 and GIP, which stimulate insulin secretion in a glucose-dependent manner, and it is primarily excreted through the fecal route with minimal renal elimination, making it unique among DPP-4 inhibitors as it doesn't require dose adjustment in patients with renal impairment.
Key Points
- The primary mechanism of action of linagliptin is the inhibition of DPP-4, which increases the levels of GLP-1 and GIP, enhancing insulin secretion and suppressing glucagon release in a glucose-dependent manner 1.
- Linagliptin is primarily excreted through the fecal route (approximately 85%) with minimal renal elimination (less than 5%), which distinguishes it from other DPP-4 inhibitors and eliminates the need for dose adjustments in patients with renal impairment 1.
- This glucose-dependent action of linagliptin reduces the risk of hypoglycemia, as it works more effectively when blood glucose levels are elevated and has minimal effect when glucose levels are normal 1.
- Linagliptin is administered as a 5 mg oral tablet once daily and can be taken with or without food, making it a convenient option for type 2 diabetes management 1.
- Its long half-life of approximately 100 hours allows for consistent 24-hour DPP-4 inhibition with once-daily dosing, contributing to its efficacy in managing type 2 diabetes 1.
Clinical Considerations
- The unique pharmacokinetic profile of linagliptin, with its primary fecal excretion and minimal renal elimination, makes it an attractive option for patients with renal impairment, as it does not require dose adjustments based on renal function 1.
- The glucose-dependent mechanism of action of linagliptin reduces the risk of hypoglycemia, making it a safer option for patients, especially when compared to other antidiabetic medications that can cause hypoglycemia regardless of blood glucose levels 1.
- Linagliptin can be used as monotherapy or in combination with other antidiabetic medications, offering flexibility in treatment regimens for type 2 diabetes management 1.
From the FDA Drug Label
12 CLINICAL PHARMACOLOGY
1 Mechanism of Action Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation Both incretin hormones are involved in the physiological regulation of glucose homeostasis.
3 Pharmacokinetics The pharmacokinetics of linagliptin has been characterized in healthy subjects and patients with type 2 diabetes mellitus. After oral administration of a single 5 mg dose to healthy subjects, peak plasma concentrations of linagliptin occurred at approximately 1. 5 hours post dose (Tmax); the mean plasma area under the curve (AUC) was 139 nmol*h/L and maximum concentration (Cmax) was 8. 9 nmol/L. Plasma concentrations of linagliptin decline in at least a biphasic manner with a long terminal half-life (>100 hours), related to the saturable binding of linagliptin to DPP-4.
The mechanism of action of Linagliptin is as a DPP-4 inhibitor, which increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation. The excretion of Linagliptin is characterized by a long terminal half-life (>100 hours) due to its saturable binding to DPP-4, and its elimination phase does not contribute to the accumulation of the drug 2.
From the Research
Mechanism of Action
- Linagliptin is a highly selective inhibitor of dipeptidyl peptidase-4 (DPP-4) 3, 4, 5, 6, 7
- By inhibiting the DPP-4 enzyme, linagliptin slows the inactivation of incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) 4, 6
- This results in a glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion, leading to a reduction in blood glucose levels 4, 6
Excretion
- Linagliptin is eliminated predominantly via a nonrenal route, making it suitable for use in patients with renal impairment without the need for dose adjustment 3, 4, 5, 6, 7
- The nonrenal route of elimination is primarily via the biliary/hepatic route 6, 7
- No dose adjustment is required in patients with hepatic insufficiency, as well as in elderly or obese patients 4, 5