Insulin degludec (Tresiba) and insulin glargine (Lantus, Toujeo, Basaglar, Semglee, Rezvoglar) are both long-acting basal insulins, but they have meaningful differences. Degludec lasts more than 42 hours with no clinical peak and allows flexible dose timing 8 to 40 hours apart. Glargine U-100 lasts about 24 hours and is best taken at the same time daily; glargine U-300 (Toujeo) lasts about 36 hours. Head-to-head trials show similar A1C but about 25 to 30 percent fewer nocturnal lows with degludec. Cost and insurance coverage usually favor glargine.
The Two Insulin Families
Long-acting basal insulin analogs replaced NPH (intermediate-acting insulin) over the past two decades because they provide steadier, more predictable background insulin coverage with fewer overnight lows. The two dominant basal analog families are:
- Insulin glargine — first launched as Lantus in 2000; biosimilars Basaglar, Semglee, and Rezvoglar are now available; Toujeo is the U-300 concentrated form launched in 2015
- Insulin degludec — launched as Tresiba in the United States in 2015; not yet available as a biosimilar
How They Are Made Differently
The structural differences explain the pharmacokinetic differences:
- Insulin glargine: Two amino acid changes (substitution at A21 and addition of two arginines at B30) shift the insulin’s isoelectric point. Glargine is soluble in the acidic pH of the formulation but precipitates as microcrystals in the neutral pH of subcutaneous tissue, then dissolves slowly over 24 hours.
- Insulin degludec: Single amino acid removal (threonine at B30) plus a fatty acid (hexadecanedioic acid) attached to lysine at B29. Degludec forms long multihexamer chains at the injection site and releases single molecules slowly, with additional reversible albumin binding in blood, producing a profile greater than 42 hours.
Pharmacokinetics Side-by-Side
| Property | Degludec (Tresiba) | Glargine U-100 (Lantus, Basaglar, Semglee, Rezvoglar) | Glargine U-300 (Toujeo) |
|---|---|---|---|
| Onset of action | 30 to 90 min | 1 to 3 hr | 1 to 6 hr |
| Peak | No peak | Near-flat (small subtle peak) | Near-flat (more uniform than U-100) |
| Duration | >42 hours | ~24 hours | ~36 hours |
| Steady state | 3 to 4 days | 2 to 4 days | 3 to 4 days |
| Concentrations available | U-100 and U-200 | U-100 | U-300 |
| Half-life | ~25 hours | ~12 hours | ~19 hours |
| Dosing flexibility | 8 to 40 hours between doses | Same time daily | Up to 3 hours either side of usual time |
Clinical Trial Evidence
BEGIN Trials (degludec vs glargine, A1C and hypoglycemia)
- BEGIN Basal-Bolus T1 and BEGIN Basal-Bolus T2 — A1C reductions similar between degludec and glargine in both type 1 and type 2 diabetes
- About 25 percent fewer nocturnal hypoglycemia events with degludec
- Similar weight gain between the two insulins
SWITCH 1 and SWITCH 2 (double-blind crossover)
- SWITCH 1 (type 1 diabetes, n=501) — degludec produced 36 percent lower rates of severe and confirmed symptomatic hypoglycemia versus glargine, with significantly fewer nocturnal events
- SWITCH 2 (type 2 diabetes, n=720) — degludec produced 30 percent lower hypoglycemia rates overall and 42 percent lower nocturnal hypoglycemia versus glargine
DEVOTE Trial (CV outcomes)
- Marso SP, et al. New England Journal of Medicine 2017 — 7,637 adults with type 2 diabetes at high cardiovascular risk randomized to degludec or glargine U-100
- Primary outcome of major adverse cardiovascular events: degludec non-inferior to glargine (hazard ratio 0.91, p<0.001 for non-inferiority)
- Degludec had 40 percent lower rate of severe hypoglycemia and 53 percent lower rate of nocturnal severe hypoglycemia versus glargine
Side Effects
Both degludec and glargine share the typical insulin side-effect profile:
- Hypoglycemia (low blood sugar) — most common with both; degludec has lower nocturnal rate
- Weight gain — modest, similar between the two
- Injection site reactions — redness, itching, small lumps
- Lipodystrophy from repeated injections in the same spot
- Peripheral edema, especially when combined with thiazolidinediones
- Allergic reactions — rare
- Hypokalemia — uncommon
Dosing Flexibility — A Real-World Difference
Degludec is the only basal insulin labeled for flexible dose timing. If you miss your usual time, you can inject as soon as you remember as long as at least 8 hours have passed since your last dose, and resume your usual schedule.
Glargine works best at the same time daily because its duration is closer to 24 hours. If you delay glargine by several hours, the next 24-hour window is compressed and some patients see breakthrough hyperglycemia or nocturnal lows. Toujeo (glargine U-300) has slightly more flexibility — up to 3 hours either side of the usual time — but is not as forgiving as degludec.
Cost Considerations
| Insulin | Retail Cost (Approximate) | Insurance Status |
|---|---|---|
| Tresiba (degludec) U-100 and U-200 | $300 to $500 per month | Often requires prior authorization |
| Lantus (glargine U-100, brand) | $200 to $400 per month | Widely covered; some plans prefer biosimilars |
| Basaglar / Semglee / Rezvoglar (glargine biosimilars) | $100 to $300 per month | Preferred formulary at many plans |
| Toujeo (glargine U-300) | $300 to $400 per month | Often requires prior authorization |
Federal Medicare Part D caps covered insulins at $35 per month as of 2023. Manufacturer copay cards, patient assistance programs, and Walmart/Costco generic options can further reduce cost.
When Degludec May Be Preferred
- History of nocturnal hypoglycemia on glargine
- Shift work or rotating schedules
- Frequent travel across time zones
- Older adults at higher risk of severe hypoglycemia
- Need for high-dose basal insulin (U-200 reduces injection volume)
- Type 2 diabetes with cardiovascular disease (DEVOTE data)
When Glargine May Be Preferred
- Insurance coverage favors glargine
- Lower out-of-pocket cost with biosimilars
- Consistent same-time-daily routine
- Long-term success on glargine without nocturnal lows
- Pregnancy — insulin detemir, NPH, and glargine have more pregnancy data; degludec has limited human pregnancy data
Switching Between Them
- From once-daily glargine U-100 to degludec: typically unit-for-unit, then titrate based on fasting glucose
- From glargine U-300 (Toujeo) to degludec: reduce dose by 20 percent at switch, then titrate
- From twice-daily glargine to degludec: reduce total daily dose by 20 percent
- From degludec back to glargine: usually unit-for-unit, with attention to fasting glucose
- Always switch with prescriber oversight and frequent self-monitoring during the first 1 to 2 weeks
Related Reading
For more, see our deep dives on Tresiba (insulin degludec), the broader treatment overview, and A1C levels.
The Bottom Line
Insulin degludec (Tresiba) and insulin glargine (Lantus, Toujeo, Basaglar, Semglee, Rezvoglar) achieve similar A1C control as basal insulins. Degludec has a duration greater than 42 hours, no peak, and uniquely flexible dose timing 8 to 40 hours apart, plus about 25 to 30 percent fewer nocturnal hypoglycemia events in head-to-head trials. Glargine has wider availability, biosimilar competition, and lower cost. DEVOTE confirmed cardiovascular safety for degludec versus glargine in high-risk type 2 diabetes. The right choice depends on hypoglycemia history, schedule, cost, and insurance coverage — talk to your prescriber to individualize.
