Pharmacotherapy: Diabetes Mellitus-Insulin Therapy!

PHARMACOTHERAPY

Medications classifications include:

1.  Sulfonyl Urea's
2. Nonsylfonylurea Secretagogues (a-Glinides)
3. Biguanides
4. Thiazolidinediones
5. a-Glucosidase Inhibitors
6. Dipeptidyl Peptidase-4 Inhibitors (Gliptins)
7. Sodium-glucose co-transporter (SGLT) Inhibitors 
8. Central-Acting Dopamine Agonists
9. Bile Acid Sequestrants
10. Insulin therapy

10. INSULIN THERAPY

• Insulin is used for the primary treatment in T1DM.
• Insulin is used in all types of DM and has no specific maximum dose.
• Insulin is the primary treatment in T1DM, and injected amylin can be added to decrease fluctuations in blood glucose levels.
• Insulin is available in various formulations. Most formulations are available as U-100, indicating a concentrations of 100unit/mL.

Types:

• Insulin is divided into two main classes:

                1. Basal Insulin                                                                             2. Bolus insulin

Storage:

• Insulin is typically refrigerated, and most vials are good for 28 days at room temperature. 
• Insulin detemir can be stored at room temperature for 42 days.

Route of Administration:

• Most common route of administration is Subcutaneous injection using a syringe or a pen device.
• Patients should be educated to rotate their site of injection administrations to minimize lipohypertrophy(a buildup of fat that decreases or prevents proper insulin absorption).
• The fastest absorption occurs in the Abdomen and the slowest in the buttocks.

Insulin Devices:

• Insulin syringes are distinguished according to the syringe capacity, syringe markings, needle Guage and length.
• Insulin pens are self-contained systems of insulin delivery. The primary advantage of Pen system is that patients do not have to draw up the dose from the Insulin vial.

*Only Insulin that can be administered IV -- Regular or Human Insulin*

*Rapid Acting Insulins are-- Insulin Aspart, Insulin Glulisine, Insulin Lispro*

1.BOLUS INSULIN (covers insulin response to meals):

Regular Insulin:

• Regular insulin is unmodified crystalline insulin commonly referred to as Neutral or Human Insulin.
• It is a clear solution that has relatively short onset and duration of action and is designed to cover insulin response to meals.
• On SC injection, Regular insulin forms small aggregates called Hexamers that undergo conversion to Dimers followed by Monomers before systemic absorption can occur.
• Patients should be counselled to inject insulin SC 30 minutes before consuming a meal.
• It is the only insulin administered IV.
• Three rapidly acting insulins approved by United States are Aspart, Glulisine, and Lispro. Substitution of one or two amino acids in regular insulin results in the unique pharmacokinetic properties characteristics of these agents.

2.Basal Insulin (Covers insulin response in between the meals and overnight):

Intermediate Duration Insulin:

• Neutral Protamine Hagedorn, better known as NPH insulin is prepared by a process in which protamine is conjugated with regular insulin, rendering a product with delayed onset but extended duration of action and is designed to cover insulin requirements between meals and/or overnight.
• With the advent of the long-acting insulins, NPH insulin use has been declined because of the inability to predict accurately when peak effects occur and a duration of action less then 24hr.
• Additionally, Protamine is a foreign protein that may increase the possibility of an allergic reaction.
• NPH insulin can be mixed with regular insulin and used immediately or stored for future use up to 1 month at room temperature or 3 months in refrigerator.
• NPH can be mixed with either Aspart or Lispro insulins, but it must be injected immediately after mixing.
• Whenever mixing insulin products with NPH, the shorter acting insulin should be drawn into the syringe first.

Long-duration Insulin:

Glargine and Detemir are designed once daily dosing basal Insulin.

• Insulin Glargine differs from regular insulin by three amino acids, resulting in a low solubility at physiologic pH.
• Detemir binds to albumin in the plasma, which gives it sustained action.
• Neither Glargine nor Detemir can be administered IV or mixed with other insulin products.
• Both Glargine and Detemir have been shown to produce slower, more prolonged absorption and a relatively constant concentration over 24hr as compared with NPH.

Combination Insulin Products:

• NPH is available in combinations of 70/30 (70% NPH & 30% Regular insulin). and 50/50 (50% NPH & 50% Regular insulin).
• Two short-acting insulin analog mixtures are also available;

1. Humalog mix 75/25 contains 75% insulin lispro protamine suspension and 25% insulin lispro.
2. Novolog mix 70/30 contains 70% insulin aspart protamine suspension and 30% insulin aspart.