The goal of insulin therapy for patients with diabetes is to provide coverage that most closely resembles endogenous insulin production and results in the best glycemic control without hypoglycemia. Although daytime control of hyperglycemia may be accomplished with bolus doses of rapid-acting insulin analogs, elevations in fasting glucose may remain a problem. If fasting blood glucose levels remain elevated, the basal insulin dose (intermediate or long-acting) may have to be adjusted.
Most insulins used today are recombinant DNA human insulins. Produced through genetic engineering, synthetic human insulin is "manufactured" by yeast or nonpathogenic E. coli. In recent years, pharmaceutical companies have developed several new types and formulations of insulin.
Different insulins are distinguished by how quickly they are absorbed, the time and length of peak activity, and overall duration of action. Onset, peak, and duration of action times are approximate and vary according to individual factors such as injection site, blood supply, concurrent illnesses, lifestyle, and exercise level. These factors can vary from patient to patient and can vary in any patient from day to day.
There are 5 kinds of insulins: rapid-acting, short-acting, intermediate-acting, long-acting, and combination insulins.
Rapid-Acting Insulins
Rapid-acting insulins are analogs of regular insulin. An analog is a chemical structure very similar to another but differing in one component. Admelog/Humalog/Lyumjev (lispro), Apidra (glulisine), and Fiasp/Novolog (aspart) are rapid-acting insulin analogs. The amino acid sequences of these analogs are nearly identical to human insulin. They differ in the positioning of certain proteins, which allows them to enter the bloodstream rapidly—within 15 min of subcutaneous injection. This closely mimics the body’s own insulin response and allows greater flexibility in eating schedules for diabetic patients. Also, because these insulins leave the bloodstream quickly, the risk of hypoglycemic episodes several hours after the meal is lessened. The peak time for rapid-acting insulins is 1–2 hr and the duration is 3–4 hr. Rapid-acting insulin solutions are clear. Insulin aspart, insulin glulisine, and insulin lispro (100 units/mL only) can be given intravenously in selected situations under medical supervision.
Short-Acting Insulins
Regular insulin is a short-acting insulin and is available commercially as Humulin R or Novolin R. The onset of regular insulin is 0.5–1 hr; its peak activity occurs 2–4 hr after subcutaneous injection and its duration of action is 5–7 hr. This time/action profile makes rigid meal scheduling necessary, as the patient must estimate that a meal will occur within 45 min of injection. Short-acting insulin solutions are clear. Regular insulin (100 units/mL only) can be given intravenously.
Intermediate-Acting Insulins
Intermediate-acting insulin contains protamine, which delays onset, peak, and duration of action to provide basal insulin coverage. Basal insulins are given to control blood glucose levels throughout the day when not eating. Commercially, intermediate-acting insulins are available as Humulin N or Novolin N. (The "N" stands for NPH.) Action starts between 2 and 4 hr after injecting. Peak activity occurs between 4 and 10 hr. Duration of action lasts 10–16 hr. The addition of protamine causes the cloudy appearance of intermediate-acting insulins and results in the formulation being a suspension rather than a solution. This is why these insulins must be gently mixed before administering. Intermediate-acting insulins can be mixed with short- or rapid-acting insulins to provide both basal and bolus coverage. Intermediate-acting insulins should not be administered intravenously.
Long-Acting Insulins
Long-acting insulins have the most delayed onset and the longest duration of all insulins. Products include Basaglar/Lantus/Semglee/Toujeo (glargine), Levemir (detemir), and Tresiba (degludec). Peaks are not as prominent in long-acting insulins. In fact, insulin glargine has no real peak action because it forms slowly dissolving crystals in the subcutaneous tissue. The onset of action of insulin glargine and insulin detemir is 3–4 hr and for insulin degludec is within 2 hr after subcutaneous injection. Full activity occurs within 4 to 5 hr and remains constant for 24 hr. Even though these insulins are clear solutions, they cannot be diluted or mixed with any other insulin or solution. Mixing these insulins with other insulin products can alter the onset of action and time to peak effect. If bolus insulin is to be given at the same time as insulin glargine, insulin detemir, or insulin degludec, two separate syringes and injection sites must be used. Long-acting insulins should not be administered intravenously.
Combination Insulins
Various combinations of premixed insulins are available, containing fixed proportions of two different insulins, usually a short- and an intermediate-acting insulin. Typically the intermediate-acting insulin makes up 70–75% of the mixture, with rapid- or short-acting insulin making up the remainder. Onset, peak, and duration vary according to each specific product. Brand names of these products include Humulin 70/30 (70% NPH, 30% regular), Humalog Mix 75/25 (75% insulin lispro protamine suspension and 25% insulin lispro), Humalog Mix 50/50 (50% insulin lispro protamine suspension and 50% insulin lispro), and Novolin 70/30 (70% NPH, 30% regular), or Novolog Mix 70/30 (70% insulin aspart protamine suspension and 30% insulin aspart).
| BRAND NAME | GENERIC NAME | TYPE OF INSULIN | ONSET/PEAK/DURATION |
|---|---|---|---|
| Humalog Mix 75/25 Humalog Mix 50/50 | insulin lispro protamine suspension & insulin lispro injection mixtures | Combination | 15–30 min/2.8 hr/24 hr |
| Novolog Mix 70/30 | insulin aspart protamine suspension & insulin aspart injection mixtures | Combination | 15 min/1–4 hr/18–24 hr |
| Humulin 70/30 Novolin 70/30 | NPH/regular insulin mixture NPH/regular insulin mixture | Combination Combination | 30 min/2–12 hr/24 hr 30 min/2–12 hr/24 hr |
| Apidra | insulin glulisine | Rapid-Acting | Within 15 min/1–2 hr/3–4 hr |
| Admelog, Humalog, or Lyumjev | insulin lispro | Rapid-Acting | Within 15 min/1–2 hr/3–4 hr |
| Fiasp or Novolog | insulin aspart | Rapid-Acting | Within 15 min/1–2 hr/3–4 hr |
| Humulin R Novolin R | regular insulin (SUBQ) regular insulin (SUBQ) | Short-Acting Short-Acting | ½–1 hr/2–4 hr/5–7 hr ½–1 hr/2–4 hr/5–7 hr |
| Humulin R Novolin R | regular insulin (IV) regular insulin (IV) | Short-Acting Short-Acting | 10–30 min/15–30 min/30–60 min 10–30 min/15–30 min/30–60 min |
| Humulin N Novolin N | NPH NPH | Intermediate-Acting Intermediate-Acting | 2–4 hr/4–10 hr/10–16 hr 2–4 hr/4–10 hr/10–16 hr |
| Levemir | insulin detemir | Long-Acting | 3–4 hr/3–14 hr/6–24 hr |
| Basaglar, Lantus, Semglee, or Toujeo | insulin glargine | Long-Acting | 3–4 hr/No Peak/24 hr |
| Tresiba | insulin degludec | Long-Acting | Within 2 hr/12 hr/up to 42 hr |