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type1.science

Insulin degludec (Tresiba)

Novo Nordisk

An ultra-long-acting basal insulin with a ~25-hour half-life and a flat, stable glucose-lowering effect lasting beyond 42 hours — its standout feature is four-times lower day-to-day variability than glargine U-100, which translates into less nocturnal hypoglycemia and unusual forgiveness around dose timing.

Available nowRegulator-approvedbasallong-acting

The scorecard

Onset speed50

Basal convention (onset is not the goal): a slow, gradual rise to steady state over 3-4 days is exactly what a basal should do — scored neutrally against basal peers rather than penalized.

Time to peak85

Basal convention (flat/peakless scores HIGH): at steady state the glucose-lowering effect is essentially flat and evenly distributed across 24 h, with very low peak-to-trough swing — close to the basal ideal.

Short tail80

Basal convention (long, smooth coverage is good): a ~25-h half-life and >42-h duration give strong day-to-day overlap, so a late or early dose leaves no coverage gap — its forgiveness is a strength here, not stacking risk.

Consistency90

Degludec's headline advantage: clamp studies show ~4x lower day-to-day variability in glucose-lowering effect than glargine U-100 (within-subject CV ~20% vs ~82%) — the most predictable basal in routine use.

Exercise flexibility58

Steady, predictable background is helpful and exercise-related hypoglycemia risk matches glargine, but its multi-day duration means the basal cannot be dialed back quickly for planned activity — manage exercise with carbs/bolus, not basal cuts.

Access & cost65

Access convention (cheaper/more available is better): approved and stocked across all six major markets and pump-independent, but brand-dominant with a high US list price; an unbranded biologic (not a true biosimilar) at a steep discount off list and copay-cap programs ease cost.

Insulins are scored relative to their role peers (see tags: rapid, ultra-rapid, basal, inhaled). A basal insulin's onset score compares it to other basals, not to mealtime insulins.

The full picture

Insulin degludec is an ultra-long-acting basal (background) insulin. You take it once a day to cover the body's around-the-clock insulin needs, separate from the rapid mealtime insulin you take with food. It is not a mealtime insulin — its job is to be slow, flat, and steady.1

Why it lasts so long. Degludec is human insulin modified so that, after a subcutaneous injection, it self-assembles into long chains of soluble multihexamers that form a depot under the skin. Insulin then peels off this depot slowly and continuously, which is what stretches its action out over days rather than hours.2

How fast, and how long — the real numbers. Degludec has a steady-state half-life of about 25 hours, independent of dose, and a duration of action of at least 42 hours.3 It reaches steady state after 3-4 days of once-daily dosing; at steady state the median time to maximum concentration is about 9 hours, but the key point is that the glucose-lowering effect is evenly distributed and flat across the 24-hour day with a very low peak — so for practical purposes it behaves as a near-peakless basal.3 Onset is gradual and is not the point for a basal insulin.

Its signature strength: predictability. In rigorous glucose-clamp studies, degludec's day-to-day variability in glucose-lowering effect was about four times lower than insulin glargine U-100 (within-person coefficient of variation ~20% vs ~82% for total effect; ~18% vs ~60% for peak effect).4 That steadiness is not just a lab finding — in the SWITCH 1 trial in people with type 1 diabetes, degludec cut overall symptomatic hypoglycemia (rate ratio 0.89) and nocturnal hypoglycemia (rate ratio 0.64) versus glargine U-100, and fewer people had a severe low (10.3% vs 17.1%).5

Forgiving dose timing. Because coverage from one dose overlaps the next, timing is flexible. In the BEGIN: Flex T1 trial, degludec given with intervals varying from 8 to 40 hours between doses controlled glucose as well as same-time-every-day dosing — useful for shift workers or anyone with an irregular schedule. The label simply asks for at least 8 hours between injections.6

Around exercise. Exercise-related hypoglycemia risk with degludec is low and similar to glargine.7 But its multi-day duration is a double-edged sword: you cannot quickly cut the basal for a planned workout the way a pump user can, so activity is best managed with extra carbohydrate or mealtime-insulin adjustments rather than basal changes.

Delivery and approvals. It is injected by pen or syringe — not used in pumps. It comes as a U-100 FlexTouch prefilled pen, a U-100 vial, and a concentrated U-200 FlexTouch pen (same dose, half the volume).3 It was approved in Japan (2012), the EU (21 January 2013), and the US FDA (25 September 2015), and is now indicated down to age 1 year and older.89

Access and cost. Degludec is available across the US, UK, EU, Canada, Australia, and Japan. Its US list price is high,10 but Novo Nordisk also sells an unbranded biologic version of degludec at a steep discount off list (not a true biosimilar, but the same molecule), and monthly copay-cap programs are available.11 No independent biosimilar competitor has launched yet.

What's coming. The frontier for degludec is once-weekly basal insulin: insulin icodec, a separately developed ultra-long molecule, aims to replace daily basal injections entirely, and degludec is the benchmark it is measured against. Degludec itself also anchors fixed-ratio combinations (with the GLP-1 drug liraglutide) and remains the basal of choice when steadiness and timing-forgiveness matter most.1

References

  1. Vora J, Cariou B, Evans M, et al. Clinical use of insulin degludec. Diabetes Res Clin Pract (2015). https://doi.org/10.1016/j.diabres.2015.04.002 ↩ ↩2

  2. Gough SCL, Harris S, Woo V, Davies M. Insulin degludec: overview of a novel ultra long-acting basal insulin. Diabetes Obes Metab (2013). https://doi.org/10.1111/dom.12052 ↩

  3. Novo Nordisk. TRESIBA (insulin degludec injection) US Prescribing Information — Clinical Pharmacology (12.2, 12.3) and Dosage Forms (3). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e8ccd2f4-6ba9-4839-87f8-4742dc9b1c17 ↩ ↩2 ↩3

  4. Heise T, Hermanski L, Nosek L, et al. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab (2012). https://doi.org/10.1111/j.1463-1326.2012.01627.x ↩

  5. Lane W, Bailey TS, Gerety G, et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized Clinical Trial. JAMA (2017). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817477/ ↩

  6. Mathieu C, Hollander P, Miranda-Palma B, et al. Efficacy and safety of insulin degludec in a flexible dosing regimen vs insulin glargine in patients with type 1 diabetes (BEGIN: Flex T1). J Clin Endocrinol Metab (2013). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612802/ ↩

  7. Heise T, Bain SC, Bracken RM, et al. Similar risk of exercise-related hypoglycaemia for insulin degludec to that for insulin glargine in patients with type 1 diabetes: a randomized cross-over trial. Diabetes Obes Metab (2016). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063138/ ↩

  8. European Medicines Agency. Tresiba (insulin degludec) — European Public Assessment Report (EPAR). https://www.ema.europa.eu/en/medicines/human/EPAR/tresiba ↩

  9. Drugs.com. Tresiba (insulin degludec) FDA Approval History (first approved 25 September 2015). https://www.drugs.com/history/tresiba.html ↩

  10. NovoCare. Tresiba (insulin degludec) injection — List Price & Insurance Coverage. https://www.novocare.com/diabetes/products/tresiba/explaining-list-price.html ↩

  11. Pharmacy Times. Novo Nordisk Launches Tresiba Unbranded Biologic Insulin to Expand Affordability Options (unbranded biologic at ~65% off the branded list price). https://www.pharmacytimes.com/view/novo-nordisk-launches-tresiba-biologic-analog-insulin-to-expand-affordability-options ↩