Basal insulin

See Also

Definitions

Insulin
1. Insulin is a polypeptide produced by pancreatic beta cells, with release stimulated by Blood Glucose concentration
2. Insulin promotes energy utilization via Glycolysis, and energy storage as glycogen, Protein and Triglycerides
3. First used in Diabetes Mellitus in 1922, by Drs Banting and Best
Bolus Insulin (short-acting)
1. Similar to physiologic Insulin, with immediate onset (15-30 min) and short duration (2 to 4 hours)
2. Primarily covers short-term Blood Glucose spikes with meals
Basal insulin (long-acting)
1. Long-acting coverage to maintain Blood Glucose control throughout the day, between meals
2. Mimics the low level continuous Insulin release by a normal human Pancreas
3. Insulin Glargine (Lantus) and similar agents that last approximately 24 hours have largely replaced NPH Insulin (12 hour duration)
Insulin Analog
1. Historically, short-acting Regular Insulin has been sourced from animal Pancreas (pigs, cows)
2. As of the 1980s, human Insulins were synthesized in Bacteria
3. Synthetic Insulins have since been modfied for rapid onset bolus (e.g. Lispro) and longer-acting basal (e.g. Glargine)

Indications

Type 1 Diabetes Mellitus
1. Basal insulin for those not using an Insulin Pump (or for emergency use when Insulin Pump fails)
Type 2 Diabetes Mellitus with Insulin Resistance refractory to non-Insulin therapy

Precautions

Insulin Dosing in the U.S. has become unconscionably expensive
1. Consider NPH Insulin (still $25 per vial at Walmart as of 2024) for basal control instead of analogs
Basal insulin does not cover meal times
1. Use Bolus Insulin for meal time coverage
Use in combination with agents to cover meals
1. Rapid acting Insulin (e.g. Lispro)
2. Oral agents (Sulfonylureas, Metformin, Glitazone) or
  1. Switch to basal/bolus when Glargine >0.5 units/kg

Mechanism

See Insulin

Medications
Analog Basal Insulin U-100

Insulin Glargine U-100 (Lantus, Basaglar, Semglee)
1. Information below is based on Lantus
2. Pharmacokinetics
  1. Most closely matches 24 hour coverage
  2. Onset: 1-2 hours
  3. Duration: 21 to 24 hours
  4. Peak: No peak (flat action curve mimics continuous Insulin Infusion)
3. Semglee (Insulin Glargine-yfgn U-100) is considered interchangeable biosimilar to Lantus as of 2021 in U.S.
  1. Allows pharmacists to auto-substitute Semglee (one third Lantus cost) for Lantus
  2. (2021) Presc Lett 28(9): 51
Insulin Degludec (Tresiba)
1. Available as U-100 or U-200
2. Pharmacokinetics
  1. Onset: 90 minutes
  2. No peak activity
  3. Duration: Up to 42 hours (ultra-long)
  4. Available as U-100 or U-200
Detemir U-100 (Levemir, discontinued in 2024)
1. Similar Pharmacokinetics as Lantus
2. Less burning on injection compared with Lantus
3. Binds and released from circulating albumin
4. Most consistent Basal insulin day to day
5. Duration varies by dose (twice daily may be preferred)
6. Pharmacokinetics
  1. Onset: 2-4 hours
  2. Peak: 6-8 hours
  3. Duration: 12 to 20 hours (varies by dosage)
7. Manufacturer discontinuing drug in U.S. in 2024 (for business reasons)
  1. Same total daily Detemir dose may be used when converting to other long acting agent
  2. May switch from Detemir total daily dose to any U-100 long acting Insulin (Lantus, Basaglar, Semglee)
  3. May also switch to the U-100 formulation of Insulin Degludec (Tresiba)
  4. Reduce total daily dose by 20% if patient at higher risk for Hypoglycemia
  5. (2024) Presc Lett 31(1): 4

Medications
Analog Basal Insulin U-300

Insulin Glargine U-300 (Toujeo, Toujeo Max Solostar)
1. Toujeo Solostar pen
  1. Toujeo contains 80 u/injection (450 u/pen)
  2. Toujeo Max contains 160 u/injection (900 u/pen)
  3. Both contain the same 3x Glargine Insulin concentration of Lantus)
2. Pharmacokinetics
  1. Onset: 6 hours
  2. Duration: 24 to 36 hours
3. Released in 2015 (curiously as Lantus becomes generic)
  1. Promoted as a longer acting Lantus (closer to 24 hour duration)
  2. However, more expensive ($500/month if 60 u/day); contrast with NPH at 10% of cost
4. Do not adjust Toujeo dose more often than every 3-4 days
5. Transitioning from other agents
  1. From Lantus, Basaglar daily
    1. Dose Toujeo at 110% of Lantus dose
  2. From Lantus twice daily
    1. Dose Toujeo at 100% of the Lantus dose
  3. From Detemir or NPH twice daily
    1. Dose Toujeo at 80% of total daily Basal insulin dose
6. Transitioning to other agents
  1. To Lantus or Basaglar
    1. Dose Lantus or Basaglar at 80% of Toujeo dose to start, then titrate up
7. References
  1. (2018) Presc Lett 25(8)
  2. Riddle (2014) Diabetes Care 37(10):2755-62 +PMID:25078900 [PubMed]

Medications
Traditional Basal insulins (non-analog)

NPH Insulin, Novolin N, Humulin N, Humulin L (Lente)
1. Onset: 1 to 2 hours
2. Peak: 6 to 8 hours
  1. Peak time is higher risk of hypoglcemia
  2. Consider snack at 6 hours after dose
3. Duration: 10 to 16 hours (Lente slightly longer)
4. Humulin L (Lente) discontinued in U.S. in 2006
5. Increased risk of Hypoglycemia (esp nocturnal) compared with newer analogues
6. NPH is much less expensive than analogues (still $25/vial as of 2016 at Walmart)
Humulin R U-500 (500 units/ml, green)
1. Indicated for those with very high Insulin requirements (>200 units per day)
2. High risk for dosing errors (very concentrated Insulin)
  1. Specific U-500 green capped syringes are available as of 2016 to reduce dosing errors
  2. Pens are preferred for less dosing errors over vials and syringes
    1. Use pen dosing window (not the number of clicks to determine dose)
    2. Each click of a U-500 pen adds 5 units of Insulin (contrast with 1 unit/click with U-100)
3. Activity is similar to Insulin 70/30
  1. Onset in 30 minutes
  2. Longer duration (>12 hours) than other Bolus Insulins
4. Divide dosing twice (60 and 40%) to three times (e.g. 40, 30 and 30%) daily
5. Do not combine with other Insulins (i.e. stop basal and mealtime Bolus Insulins)
6. References
  1. (2022) Presc Lett 29(3): 14
Ultralente Insulin (extended Insulin zinc suspension)
1. Discontinued in U.S. in 2006
2. Significant inconsistent effect even in same person
3. Onset: 6-10 hours
4. Peak: No peak
5. Duration: 18 to 24 hours

Medications
Delivery Devices - OptiClik Pen

Pens are free from Aventis
1. Phone: 800-207-8049
Pens ease Insulin delivery
Lantus in cartridges costs 2 cents/unit more than vial
(2005) Prescriber's Letter 12:32

Dosing

See Insulin Glargine (Lantus)
See Insulin Glargine U-300 (Toujeo, Toujeo Max Solostar)
See NPH Insulin
See Humulin R U-500
See Insulin Dosing
See Insulin Dosing in Type I Diabetes
See Insulin Dosing in Type II Diabetes
Only NPH Insulin may be mixed in same syringe with bolus/rapid Insulins (draw up Bolus Insulin first)
1. Do NOT mix other basal/Long-Acting Insulins (e.g. Insulin Glargine) with Bolus Insulins
Typical daily dosing
1. Basal insulins are injected subcutaneously (SQ)
2. Total daily Insulin
  1. Type 1 Diabetes: 0.3 to 0.5 units/kg (up to 0.5 to 1.0 units/kg in children)
  2. Type 2 Diabetes: 1 to 1.5 units/kg
3. Basal insulin dose
  1. Give 50% of total daily dose as Basal insulin
    1. Daily for most Analog Basal Insulins (e.g. Insulin Glargine)
    2. Twice daily for NPH Insulin (Intermediate-Acting Insulin)
  2. Give remaining 50% of total Insulin daily units as Bolus Insulin divided over 3 meals
    1. In type 2 diabetes, Basal insulin is often started without Bolus Insulin

Adverse Effects

See Insulin

Safety

Insulin is considered safe in pregnancy and Lactation

References