II. Definitions
-
Insulin
- Insulin is a polypeptide produced by pancreatic beta cells, with release stimulated by Blood Glucose concentration
- Insulin promotes energy utilization via Glycolysis, and energy storage as glycogen, Protein and Triglycerides
- First used in Diabetes Mellitus in 1922, by Drs Banting and Best
-
Bolus Insulin (short-acting)
- Similar to physiologic Insulin, with immediate onset (15-30 min) and short duration (2 to 4 hours)
- Primarily covers short-term Blood Glucose spikes with meals
- Basal insulin (long-acting)
- Long-acting coverage to maintain Blood Glucose control throughout the day, between meals
- Mimics the low level continuous Insulin release by a normal human Pancreas
- Insulin Glargine (Lantus) and similar agents that last approximately 24 hours have largely replaced NPH Insulin (12 hour duration)
- Insulin Analog
III. Indications
-
Type 1 Diabetes Mellitus
- 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
IV. Precautions
-
Insulin Dosing in the U.S. has become unconscionably expensive
- 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
- Use Bolus Insulin for meal time coverage
- Use in combination with agents to cover meals
- Rapid acting Insulin (e.g. Lispro)
- Oral agents (Sulfonylureas, Metformin, Glitazone) or
- Switch to basal/bolus when Glargine >0.5 units/kg
V. Mechanism
- See Insulin
VI. Medications: Analog Basal Insulin U-100
-
Insulin Glargine U-100 (Lantus, Basaglar, Semglee)
- Information below is based on Lantus
- Pharmacokinetics
- Most closely matches 24 hour coverage
- Onset: 1-2 hours
- Duration: 21 to 24 hours
- Peak: No peak (flat action curve mimics continuous Insulin Infusion)
- Semglee (Insulin Glargine-yfgn U-100) is considered interchangeable biosimilar to Lantus as of 2021 in U.S.
- Insulin Degludec (Tresiba)
- Available as U-100 or U-200
- Pharmacokinetics
- Onset: 90 minutes
- No peak activity
- Duration: Up to 42 hours (ultra-long)
- Available as U-100 or U-200
- Detemir U-100 (Levemir)
- Similar Pharmacokinetics as Lantus
- Less burning on injection compared with Lantus
- Binds and released from circulating albumin
- Most consistent Basal insulin day to day
- Duration varies by dose (twice daily may be preferred)
- Pharmacokinetics
- Onset: 2-4 hours
- Peak: 6-8 hours
- Duration: 12 to 20 hours (varies by dosage)
- Manufacturer discontinuing drug in U.S. in 2024 (for business reasons)
- Same total daily Detemir dose may be used when converting to other long acting agent
- May switch from Detemir total daily dose to any U-100 long acting Insulin (Lantus, Basaglar, Semglee)
- May also switch to the U-100 formulation of Insulin Degludec (Tresiba)
- Reduce total daily dose by 20% if patient at higher risk for Hypoglycemia
- (2024) Presc Lett 31(1): 4
VII. Medications: Analog Basal Insulin U-300
-
Insulin Glargine U-300 (Toujeo, Toujeo Max Solostar)
- Toujeo Solostar pen
- Pharmacokinetics
- Onset: 6 hours
- Duration: 24 to 36 hours
- Released in 2015 (curiously as Lantus becomes generic)
- Promoted as a longer acting Lantus (closer to 24 hour duration)
- However, more expensive ($500/month if 60 u/day); contrast with NPH at 10% of cost
- Do not adjust Toujeo dose more often than every 3-4 days
- Transitioning from other agents
- Transitioning to other agents
- References
- (2018) Presc Lett 25(8)
- Riddle (2014) Diabetes Care 37(10):2755-62 +PMID:25078900 [PubMed]
VIII. Medications: Traditional Basal insulins (non-analog)
-
NPH Insulin, Novolin N, Humulin N, Humulin L (Lente)
- Onset: 1 to 2 hours
- Peak: 6 to 8 hours
- Peak time is higher risk of hypoglcemia
- Consider snack at 6 hours after dose
- Duration: 10 to 16 hours (Lente slightly longer)
- Humulin L (Lente) discontinued in U.S. in 2006
- Increased risk of Hypoglycemia (esp nocturnal) compared with newer analogues
- NPH is much less expensive than analogues (still $25/vial as of 2016 at Walmart)
-
Humulin R U-500 (500 units/ml, green)
- Indicated for those with very high Insulin requirements (>200 units per day)
- High risk for dosing errors (very concentrated Insulin)
- Specific U-500 green capped syringes are available as of 2016 to reduce dosing errors
- Pens are preferred for less dosing errors over vials and syringes
- Use pen dosing window (not the number of clicks to determine dose)
- Each click of a U-500 pen adds 5 units of Insulin (contrast with 1 unit/click with U-100)
- Activity is similar to Insulin 70/30
- Onset in 30 minutes
- Longer duration (>12 hours) than other Bolus Insulins
- Divide dosing twice (60 and 40%) to three times (e.g. 40, 30 and 30%) daily
- Do not combine with other Insulins (i.e. stop basal and mealtime Bolus Insulins)
- References
- (2022) Presc Lett 29(3): 14
-
Ultralente Insulin (extended Insulin zinc suspension)
- Discontinued in U.S. in 2006
- Significant inconsistent effect even in same person
- Onset: 6-10 hours
- Peak: No peak
- Duration: 18 to 24 hours
IX. Medications: Delivery Devices - OptiClik Pen
X. 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)
- Do NOT mix other basal/Long-Acting Insulins (e.g. Insulin Glargine) with Bolus Insulins
- Typical daily dosing
- Basal insulins are injected subcutaneously (SQ)
- Total daily Insulin
- Type 1 Diabetes: 0.3 to 0.5 units/kg (up to 0.5 to 1.0 units/kg in children)
- Type 2 Diabetes: 1 to 1.5 units/kg
- Basal insulin dose
- Give 50% of total daily dose as Basal insulin
- Daily for most Analog Basal Insulins (e.g. Insulin Glargine)
- Twice daily for NPH Insulin (Intermediate-Acting Insulin)
- Give remaining 50% of total Insulin daily units as Bolus Insulin divided over 3 meals
- In type 2 diabetes, Basal insulin is often started without Bolus Insulin
- Give 50% of total daily dose as Basal insulin
XI. Adverse Effects
- See Insulin
Images: Related links to external sites (from Bing)
Related Studies
levemir (on 4/20/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
LEVEMIR 100 UNIT/ML VIAL | $29.55 per ml | |
LEVEMIR FLEXPEN 100 UNIT/ML | $29.56 per ml | |
LEVEMIR FLEXTOUCH 100 UNIT/ML | $29.58 per ml | |
insulin degludec (on 1/18/2023 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
INSULIN DEGLUDEC FLEXTOUCH 100 UNIT/ML PEN | Generic | $11.34 per ml |
INSULIN DEGLUDEC FLEXTOUCH 200 UNIT/ML PEN | Generic | $22.71 per ml |
tresiba (on 4/20/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
TRESIBA 100 UNIT/ML VIAL | $32.65 per ml | |
TRESIBA FLEXTOUCH 100 UNIT/ML | $32.55 per ml | |
TRESIBA FLEXTOUCH 200 UNIT/ML | $65.09 per ml |