LINAGLIPTIN
Clinical safety rating: safe
Animal studies have demonstrated safety
Linagliptin is a competitive, reversible inhibitor of dipeptidyl peptidase-4 (DPP-4), increasing incretin hormones (GLP-1, GIP) levels, thereby enhancing glucose-dependent insulin secretion and suppressing glucagon release.
| Metabolism | Minimally metabolized; primarily excreted unchanged in feces (80%) and urine (5%). Hepatic metabolism via CYP3A4 and FMO3 is negligible. |
| Excretion | Approximately 90% of absorbed dose is excreted unchanged in feces (biliary/fecal route), and about 5% is excreted unchanged in urine. Renal excretion is minimal (<1% as metabolites). |
| Half-life | Terminal elimination half-life is approximately 12 hours, allowing once-daily dosing. No accumulation at steady state. |
| Protein binding | Approximately 70-80% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is about 10 L (≈0.14 L/kg), indicating limited extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 30% due to first-pass metabolism. |
| Onset of Action | Oral: Onset of action occurs within 1 hour, with peak plasma concentration reached at 1-3 hours post-dose. |
| Duration of Action | Duration of action is >24 hours, providing sustained DPP-4 inhibition and glycemic control over the dosing interval. |
5 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment, including end-stage renal disease (ESRD) on dialysis. |
| Liver impairment | No dose adjustment required for any degree of hepatic impairment (Child-Pugh A, B, or C). |
| Pediatric use | Not approved for use in pediatric patients under 18 years of age; safety and efficacy not established. |
| Geriatric use | No dose adjustment required based on age; monitor renal function as part of routine care. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions May cause hypersensitivity reactions including anaphylaxis.
| Breastfeeding | No human data; present in rat milk at 3:1 ratio (milk:plasma). M/P ratio unknown in humans. Caution advised; avoid breastfeeding due to potential for infant hypoglycemia and lack of safety data. |
| Teratogenic Risk | Limited human data; animal studies show no fetal harm at exposures up to 49 times human exposure. No known teratogenic risk; FDA Pregnancy Category B. No specific first, second, or third trimester risks identified. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Common Effects | Nasopharyngitis |
| Serious Effects |
["History of serious hypersensitivity reaction to linagliptin (e.g., anaphylaxis, angioedema)","Type 1 diabetes mellitus","Diabetic ketoacidosis"]
| Precautions | ["Pancreatitis (acute and hemorrhagic)","Hypoglycemia when used with sulfonylurea or insulin","Bullous pemphigoid requiring hospitalization","Arthralgia (severe and disabling)","Heart failure risk with concomitant use in patients with established CV disease","Acute renal failure (post-marketing)"] |
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| Monitor blood glucose and HbA1c for glycemic control. Assess fetal growth and well-being via ultrasound. Monitor for hypoglycemia in mother and neonate. |
| Fertility Effects | No human studies on fertility. Animal studies show no impairment of fertility at exposures up to 100 times human exposure. |