TRESIBA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRESIBA (TRESIBA).
Long-acting basal insulin analog. Binds to insulin receptor, activating glucose transport and metabolism. Forms multi-hexamers at injection site, resulting in slow, sustained absorption.
| Metabolism | Degraded by general protein degradation pathways (proteolysis) into small peptide fragments. No significant CYP450 metabolism. |
| Excretion | Renal: minimal intact insulin degludec excretion (<1%). Fecal: following degradation, metabolites are excreted in feces (approximately 70% of total radioactivity). Biliary: minor route (approximately 20-30% of degradation products). |
| Half-life | Terminal elimination half-life of approximately 25 hours following subcutaneous administration. This extensive half-life supports once-daily dosing due to formation of soluble multihexamers at injection site, resulting in a flat and stable pharmacokinetic profile. |
| Protein binding | >99% bound to albumin. |
| Volume of Distribution | Approximately 0.35–0.4 L/kg (extrapolated from total body weight), consistent with distribution primarily into extracellular fluid. |
| Bioavailability | Subcutaneous: absolute bioavailability is approximately 100% after subcutaneous injection into the thigh, abdomen, or deltoid. |
| Onset of Action | Subcutaneous: onset of action occurs within 30–90 minutes, with a gradual and prolonged glucose-lowering effect. |
| Duration of Action | Subcutaneous: duration of action exceeds 42 hours at steady state, allowing for flexible once-daily dosing with a 8- to 40-hour dosing window. Clinical effect persists for at least 24 hours with consistent glucose lowering. |
Subcutaneous injection once daily. Start with 10 units/day in insulin-naive patients; titrate based on blood glucose levels. Maximum dose not established; typical range 10-160 units/day.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate impairment (GFR ≥30 mL/min). For severe impairment (GFR <30 mL/min), monitor blood glucose more frequently; dose reduction may be needed due to prolonged insulin action. |
| Liver impairment | No specific dose adjustment recommended for Child-Pugh Class A or B. For Class C, monitor glucose closely; may require dose reduction due to impaired glucose metabolism. |
| Pediatric use | Approved for children ≥1 year. Initial dose: 0.17-0.34 units/kg once daily in insulin-naive patients; titrate based on glycemic control. Maximum dose not defined; adjust per insulin needs. |
| Geriatric use | Start with lower doses (e.g., 5 units/day) to reduce hypoglycemia risk. Titrate carefully due to potential renal impairment and altered counterregulatory responses. Monitor glucose frequently. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRESIBA (TRESIBA).
| Breastfeeding | Insulin degludec is a large protein molecule and likely excreted into breast milk in negligible amounts. No specific M/P ratio is available. It is not orally bioavailable and would be digested in the infant's gut. Therefore, it is considered compatible with breastfeeding. The manufacturer advises caution, but no adverse effects in breastfed infants have been reported. |
| Teratogenic Risk | Insulin degludec does not cross the placenta in significant amounts. Animal studies show no direct or indirect harmful effects on fetal development. In humans, no increased risk of major congenital anomalies or adverse fetal outcomes has been observed when used during pregnancy. However, uncontrolled maternal diabetes carries risks for the fetus (e.g., macrosomia, hypoglycemia, congenital anomalies). Use during pregnancy is considered acceptable if clearly needed. First trimester: no known teratogenicity. Second and third trimesters: risk of fetal harm from poor glycemic control outweighs minimal insulin transfer. |
■ FDA Black Box Warning
Not approved for the treatment of diabetic ketoacidosis. Patients with type 1 diabetes require rapid-acting insulin.
| Common Effects | Hypoglycemia low blood glucose level Injection site reactions pain swelling redness |
| Serious Effects |
["Hypoglycemia","Hypersensitivity to insulin degludec or any excipients"]
| Precautions | ["Never share insulin pens or syringes","Monitor for hypoglycemia, especially in patients with renal or hepatic impairment","Changes in insulin regimen may affect glycemic control and precipitate hypoglycemia or hyperglycemia","Hypokalemia may occur if glucose levels are controlled too rapidly","Accidental mix-ups between insulin products can occur; verify label before administration","Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs)"] |
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| Fetal Monitoring | Monitor maternal blood glucose levels frequently to maintain tight glycemic control. HbA1c should be checked every 1-3 months. Fetal monitoring: ultrasound for growth and anatomy (especially if diabetes-related complications), fetal heart rate monitoring in third trimester, and assessment for macrosomia or polyhydramnios. Monitor for maternal hypoglycemia and ketoacidosis. Adjust insulin doses accordingly. |
| Fertility Effects | No known adverse effects on human fertility. Insulin degludec is not associated with impairment of reproductive function in animal studies. Uncontrolled diabetes negatively impacts fertility; thus, improved glycemic control may enhance fertility. |