Insulin Degludec

Tresiba improves glycemic control in patients age 1 or older with diabetes mellitus, including type 1 and type 2. Pediatric type 2 support includes extrapolation from adult evidence; the pediatric trial population had type 1 diabetes. In type 1 diabetes use concomitant short-acting insulin.

It is not recommended for diabetic ketoacidosis. It is a subcutaneous basal product, not an IV insulin, insulin-pump infusion or rapid meal / correction dose. Fixed degludec / liraglutide or degludec / aspart combinations need separate doses and indications.

Adults inject once daily at any time of day; pediatric patients inject at the same time every day. The label recommends 3–4 days between dose increases. Adults who miss a dose inject during waking hours when discovered, keeping at least 8 hours between consecutive doses. Children who miss a dose contact the clinician and check glucose more often until the next scheduled dose; do not transfer adult flexibility to children.

U-100 FlexTouch dials 1-unit increments up to 80 units per injection; U-200 dials 2-unit increments up to 160. The displayed units are the delivered units: no concentration conversion. U-200 is not a vial. For pediatric doses below 5 units / day, use the U-100 vial. Use an appropriate U-100 insulin syringe with the U-100 vial; never draw from any pen into a syringe.

Inject subcutaneously into abdomen, thigh or upper arm; rotate sites and avoid lipodystrophy / amyloid lumps. Do not dilute, mix, give IV or use in a pump. Renal / hepatic impairment requires intensified glucose monitoring and individualized adjustment, without a fixed numerical adjustment table. Meal / activity changes and illness can change insulin needs.

Do not administer during an episode of hypoglycemia. Hypersensitivity to insulin degludec or an excipient is also contraindicated. A current low-glucose episode requires treatment and an individualized insulin plan; do not simply omit basal insulin indefinitely.

The selected U.S. Tresiba label has no boxed warning. Severe / prolonged hypoglycemia, medication errors and potassium or allergic complications remain major risks.

Hypoglycemia is the principal adverse reaction. Other reported reactions include allergy, injection-site reactions, lipodystrophy, localized cutaneous amyloidosis, itching, rash, edema and weight gain. Trial definitions and populations affect reported frequencies; do not equate one trial’s rate with every patient’s risk.

Other diabetes medicines, ACE inhibitors / ARBs, salicylates, some antibiotics and MAO inhibitors may increase hypoglycemia risk. Corticosteroids, atypical antipsychotics, thyroid hormones, sympathomimetics, some diuretics or reproductive hormones may reduce glucose-lowering effect. Insulin adjustment and extra glucose checks may be needed; no fixed adjustment percentage is supplied.

Alcohol, beta-blockers, clonidine and lithium can increase or decrease insulin’s effect. Pentamidine may produce hypoglycemia followed by hyperglycemia. Beta-blockers, clonidine, guanethidine and reserpine may blunt warning symptoms; increase glucose monitoring.

Pioglitazone and other PPAR-gamma agonists can add fluid retention / heart-failure risk with insulin. Monitor weight, edema and dyspnea. Changing basal insulin, concentration, manufacturer, site or delivery device needs supervised dose review and extra glucose checks.

The label’s trial of 185 pregnant women with type 1 diabetes found no significant pregnancy or newborn outcome differences versus detemir, but small sample size and poor glucose control limit conclusions. Poorly controlled diabetes itself poses maternal / fetal risk; manage with the diabetes / pregnancy team. Human milk / infant / milk-production data for degludec are absent; balance maternal need and breastfeeding benefits with close glucose / dose review.

Safety / effectiveness are established from age 1, not below 1. Children have a fixed daily timing, reduced switch dose and separate missed-dose instructions; use the U-100 vial below 5 units / day. Older patients may be more sensitive and have harder-to-recognize hypoglycemia; initiation, increments and maintenance should be conservative.

Studies found no clinically important renal PK difference and no hepatic PK difference across studied impairment categories. Nevertheless, intensify glucose monitoring and adjust individually because insulin needs and hypoglycemia susceptibility change. Hemodialysis did not affect degludec clearance in the small studied ESRD group; this is not a dialysis-day dosing algorithm.

Insulin promotes peripheral glucose uptake and inhibits hepatic glucose production, lipolysis and proteolysis. Degludec forms multihexamers in subcutaneous tissue, slowing absorption; albumin binding contributes to prolonged action.

A steady-state clamp study found glucose-lowering action lasting at least 42 hours after the last of 8 daily 0.4 units / kg doses; this does not mean every dose guarantees 42-hour control. Steady state is reached in 3–4 days, mean steady-state half-life about 25 hours and protein binding above 99%. U-100 / U-200 exposure and glucose effect are comparable at the same units / kg. Insulin-like degradation forms inactive metabolites.

Use the prescribed glucose-monitoring plan and review fasting / overnight values, hypoglycemia, glycemic-control markers and injection sites. Increase checks during initiation, titration, switching, illness or organ / drug changes. Check potassium when risk factors warrant and monitor edema / heart-failure symptoms with TZDs.

Verify label, concentration and displayed units before every dose. Never share or withdraw pen insulin. Rotate normal tissue sites, use a fresh needle, remove it after injection and dispose of sharps safely. Inspect for clear / colorless solution. Teach recognition / rescue of low glucose and protect driving safety; adult and pediatric missed-dose plans differ.

Excess insulin can cause prolonged hypoglycemia and hypokalemia. Mild episodes are generally treated with oral glucose according to the patient’s plan; severe episodes with seizure / unconsciousness require emergency care and glucagon or IV glucose as appropriate. Continued observation / carbohydrate may be needed after initial recovery. No universal rescue quantity or observation interval is invented.

Appearance

Clear, colorless solution · FlexTouch pen

Concentration / contents

200 units / mL · 3 mL · 600 units

Delivery

2-unit increments · up to 160 units / injection

Example package

NDC 0169-2550-13 · 3 pens

U-100 is supplied as 3 mL FlexTouch pens (300 units; up to 80 per injection) and a 10 mL multidose vial (1000 units). U-200 is a 3 mL FlexTouch pen (600 units; up to 160 per injection). Pen maxima are per injection, not patient daily-dose ceilings. Fixed combinations and other devices require separate verification.

Unused refrigerated product: 2–8°C until expiry; do not freeze or place against the cooling element. Unopened at room temperature up to 30°C: 56 days. In-use vial or either FlexTouch: 56 days at up to 30°C or refrigerated 2–8°C. Discard after that window even if insulin remains. Protect from heat / light, keep vials in the carton and pens capped without a needle; do not use frozen product.