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Medications> Glucose-lowering>
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Insulins (Basal): Intermediate- and Long-acting

Nadeen Hosein, M.D. and Brian Pinto, Pharm.D.
03-09-2011

INDICATIONS

FDA

  • Type 1 diabetes mellitus (DM1)
  • Type 2 diabetes mellitus (DM2)
  • NPH insulin: Gestational diabetes mellitus (GDM)

MECHANISM

  • Basal insulins are long acting due to prolonged absorption following subcutaneous injection.
  • Facilitates glucose uptake into muscle and fat
  • Reduces hepatic glucose output
  • Inhibits lipolysis
  • Inhibits protein breakdown and promotes protein synthesis

USUAL ADULT DOSING

  • TDD = total daily dose; U = units of insulin; SQ = subcutaneously
  • In general, when initiating insulin, 50% of the TDD is given as basal insulin, and 50% of the TDD is given as bolus insulin (divided among the three meals).  
  • Type 1 diabetes: Typical TDD for initiation is 0.2-0.5 U/kg/day and ranges from 0.4-1 U/kg/day, or more, for maintenance (see Insulin Initiation in Type 1 Diabetes)
  • Type 2 diabetes: Typical TDD for initiation is 0.1-0.2 U/kg/day, usually given all as basal insulin for the first few weeks/months before introducing bolus insulin. For maintenance, the TDD typically ranges from 0.2-1.5 U/kg/day or more, depending on the degree of insulin resistance. ( See Insulin Initiation in Type 2 Diabetes)
  • If initiating insulin using weight-based formulas, adjust doses further based on the patient's glycemic response.
  • An alternative method for starting insulin in an insulin naive patient is to start with 10 units basal insulin SQ every 24 hrs and titrate up by 2 units every 2-3 days until fasting blood sugar is at goal.
  • If switching from twice daily NPH to once daily glargine or detemir insulin, calculate total daily NPH dose and reduce by 20% to arrive at a glargine or detemir insulin dose to be given SQ every 24 hrs.
  • Some patients using glargine or detemir achieve better glycemic control with a twice daily regimen, especially at higher doses of basal insulin (i.e. more than 50 units daily).
  • For use in treating GDM, refer to "Principles of Managing Gestational Diabetes Mellitus."

FORMS

brand 
name
 
generic 
Mfg 
brand 
forms
 
cost* 
Lantusglargine insulin (recombinant analog)Sanofi-Aventis USSQ
solution, 100 U/mL, vial
10 mL vial (1000 U)
$104
      SQ
solution, 100 U/mL, Lantus SoloStar disposable prefilled pens
box of five 3 mL pens (15 mL, 1500 U)
$188
      SQ
solution, 100 U/mL, Lantus cartridges, for use in the OptiClik reusable pen which must be obtained separately
box of five 3 mL cartridges (15 mL, 1500 U)
$191
Levemirdetemir insulin (recombinant analog)Novo NordiskSQ
solution, 100 U/mL, vial
10 mL vial (1000 U)
$103
      SQ
solution, 100 U/mL, Levemir FlexPen disposable prefilled pens
box of five 3 mL pens (15 mL, 1500 U)
$191
Humulin NNPH insulin (recombinant human insulin, isophane suspension)Eli LillySQ
suspension, 100 U/mL, vial
10 mL vial (1000 U)
$57
      SQ
suspension, 100 U/mL, Humulin N disposable prefilled pens
box of five 3 mL pens (15 mL, 1500 U)
$154
Novolin NNPH insulin (recombinant human insulin, isophane suspension)Novo NordiskSQ
suspension, 100 U/mL, vial
10 mL vial (1000 U)
$58

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

DOSING IN SPECIAL POPULATIONS

RENAL

  • Dose reductions may be needed since insulin is metabolized by the kidneys, and may have a longer half life in patients with renal impairment.
  • Glargine insulin has active metabolites which may result in enhanced hypoglycemia for patients with renal impairment.
HEPATIC

  • Dose reductions may be needed, since insulin is metabolized by the liver and also because most gluconeogenesis occurs in the liver.
PREGNANCY

  • Glargine and detemir insulins: FDA Category C
  • NPH insulin: FDA Category B. However, this is the only basal insulin that has received FDA approval for use in treating GDM
BREASTFEEDING

  • Glargine and detemir insulins: Thomson Lactation Ratings: infant risk cannot be ruled out
  • NPH insulin: unknown risk

ADVERSE DRUG REACTIONS

GENERAL

  • Contraindicated for intravenous administration
  • Not for use in insulin pumps
COMMON

  • Hypoglycemia
  • Injection site pain, noted particularly with glargine insulin since it is an acidic solution
  • Weight gain
OCCASIONAL

  • Local injection site reactions (redness, itching, swelling)
  • Lipoatrophy (loss of subcutaneous adipose tissue) at injection site (to avoid, rotate injection sites frequently)
  • Lipohypertrophy (accumulation of subcutaneous adipose tissue) at injection site (to avoid, rotate injection sites frequently)
RARE

  • Immune hypersensitivity reactions
  • Hypokalemia

DRUG INTERACTIONS

  • Any drug which also lowers blood glucose (e.g. sulfonylureas) when used in a patient on insulin may result in additive hypoglycemia

PHARMACOKINETIC

COMMENTS

  • NPH (the "cloudy" insulin) can be safely mixed with rapid acting insulins. To do so, advise patient to first draw up the clear rapid acting insulin into the syringe, then draw up the cloudy NPH insulin second. Tell patients to draw up "clear first, then cloudy second," in that order.
  • Glargine and detemir must never be mixed with other insulins, as the change in pH will affect their potency.
  • Most patients prefer using insulin pens (disposable ones, or reusable ones with replaceable insulin cartridges) to drawing up insulin from traditional vials using syringes. Insulin pen needles must be prescribed and purchased separately, as they do not come packaged with the insulin pens. Refer to the "FORMS" table above to see which basal insulin preparations are available in pen form.
  • Alcohol may have a hypoglycemic effect in people taking insulin, and should be used (if at all) in moderation and with caution.
  • The "peakless" character of long-acting insulins such as glargine is, in clinical practice, not always the case. There may be a distinct maximum time of action, and insulin may not last 24 hours.
  • Detemir insulin has on average a duration of action < 20 hours, so is generally used twice daily.
  • Older basal insulins include lente and ultralente and have been discontinued.

REFERENCES

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