Generic Name

Tresiba

Mechanism

• Tresiba is a long‑acting insulin analog (glargine U300) that delivers a steady‑state release of insulin over ~72 h.
• It contains a glutamic‑acryloyl substitution at the B29 residue that prevents hexamer formation, leading to a slow, uniform absorption profile and minimal peak‑to‑peak fluctuations.

Pharmacokinetics

• Absorption: ~3–7 h to reach peak plasma concentration; no true peak due to ultra‑slow release.
• Bioavailability: ~7 % absolute oral (unused); 42 % subcutaneously.
• Half‑life: ~14 h (continuous).
• Volume of distribution: ~0.3 L/kg.
• Excretion: Kidney (renal clearance) and hepatic metabolism; no dose adjustment required for mild‑to‑moderate renal or hepatic impairment.

Indications

• Type 1 diabetes mellitus (adjunct to rapid‑acting insulin).
• Type 2 diabetes mellitus (adjunct to oral hypoglycemics or insulin).
• Insulin‑treated patients requiring a simplified basal regimen with once‑daily or twice‑daily dosing.

Contraindications

• Hypersensitivity to insulin glargine or any excipient.
• Can cause hypoglycemia; vigilance in patients with impaired counter‑regulatory responses.
• Avoid during pregnancy unless benefits outweigh risks; no definitive safety data.
• Use cautiously in patients with severe renal impairment (eGFR <30 mL/min) and adjust dosing if necessary.

Dosing

• Initiation: Start at 10–20 U/day in the evening (e.g., 09:00–11:00 pm) for insulin‑naïve patients; can start lower in frail individuals.
• Titration: Increase by 5–10 U/week based on fasting SMBG or pre‑breakfast/bedtime glucose.
• Maximum dose: 100 U/day (rarely needed).
• Injection sites: Subcutaneous abdominal wall, thigh, or buttock; rotate sites to prevent lipohypertrophy.
• Storage: 2–8 °C; can be kept out of refrigeration for ≤6 h if no staff access to a cooler is available.

Adverse Effects

• Common: Injection‑site reactions (pain, erythema), weight gain, mild edema.
• Serious: Hypoglycemia (nocturnal or post‑meal), severe allergic reactions (rash, anaphylaxis), insulinoma (rare).
• Monitoring for hypoglycemia is especially important during dose titration or in patients with renal impairment.

Monitoring

• Fasting Blood Glucose (FBG).
• Post‑prandial glucose if indicated.
• HbA1c every 3 months.
• Weight and BMI evolution.
• Renal and liver function in patients with comorbidities.
• Electrolytes if recurrent hypoglycemia or symptomatic hyperkalemia.

Clinical Pearls

• Day‑night flexibility: Because of its minimal peak, Tresiba can be given in the morning or evening with comparable glycemic control; switching daily timing is generally safe.
• Beyond basal insulin: If a patient requires rapid‑acting insulin post‑meal, Tresiba pairs well with U-10/-20 rapid agents without overlapping peaks.
• Avoided in adrenaline‑secreting tumors because hypoglycemia risk increases.
• Improves ‘time in range’ (TIR) in patients with erratic activity patterns or shift work, due to its long half‑life.
• Consider as a stepping stone to basal‑bolus or insulin‑pump therapy: its uniform action profile makes it a solid baseline for advanced insulin strategies.

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