Types of insulin

The approximate time of onset, peak activity, and duration of action of the available insulin preparations is shown in Figures 4.2 and 4.3. Insulin preparations vary with respect to onset and duration of action, which differ due to modifications to human regular insulin that either slow or hasten the time for it to be absorbed into the bloodstream. Relative to human regular insulin, the rapid-acting analogs (insulin lispro, insulin aspart, and insulin glulisine) have a more rapid onset of action, higher peak serum concentration, and shorter duration of action. Inhaled

Figure 4.1 Normal insulin secretion and action

Insulin secretion

* *

*

Meals

Figure 4.2 Profiles of available insulins

-- NPH

»

^ Detemir

l/\

• • «Glargine

l/l\

• • «Regular

J 1 \

-- Lispro, aspart, glulisine

1 1 \

^ Inhaled insulin

1 A i: i \

c

:

f »

N

0

6

Time (hours)

18 24

NPH, neutral protamine Hagedorn

NPH, neutral protamine Hagedorn human insulin is similar to the rapid-acting analogs in terms of its onset and peak effect. However, its effective duration is slightly longer than the analogs, and comparable to regular insulin. The two basal insulin analogs (insulin glargine and insulin detemir), have a longer duration of action, relative to human basal insulin (neutral protamine Hagedorn or NPH). Premix insulins, which contain fixed amounts of intermediate-acting insulin and short- or rapid-acting insulin, are also available. These mixtures have dual action profiles, consistent with those of the individual components. For example 100 units of 70/30 human insulin have the same effect as 70 units NPH and 30 units regular insulin.

It is important to emphasize that the characteristics outlined in Figure 4.3 are only approximations. The usually quoted data regarding time of onset and duration of action have not been determined in a standardized fashion. Subcutaneous insulin absorption can be affected by multiple factors including the size ofthe subcutaneous depot, injection technique, the site of injection, and blood flow. Inhaled insulin has variable absorption characteristics in smokers and in patients with underlying lung disease [4]. In addition, conditions such as impaired renal function can increase the effective duration of action of the administered insulin. Due to these multiple factors, insulin profiles vary significantly from patient to patient. For example, a single daily dose of NPH may be sufficient to last an entire day for one patient, while other patients may require additional injections. Furthermore, variable absorption in the same patient, from day to day, may lead to fluctuations in glycemic control.

Figure 4.3 Approximate duration of action of insulin preparations

Insulin

Onset of action

Peak action

Effective duration

Rapid-acting

Insulin aspart

5-15 min

30-90 min

<5 h

Insulin lispro

5-15 min

30-90 min

<5 h

Insulin glulisine

5-15 min

30-90 min

<5 h

Insulin inhalation powder

5-15 min

30-90 min

5-8 h

Short-acting

Regular insulin

30-60 min

2-3 h

5-8 h

Intermediate-acting

NPH insulin

2-4 h

4-10 h

10-16 h

Long-acting

Insulin glargine

2-4 h

None

20-24 h

Insulin detemir

3-8 h

None

6-23 h

NPH, neutral protamine Hagedorn. Adapted from reference [5].

NPH, neutral protamine Hagedorn. Adapted from reference [5].

Although it has been proposed that pharmacokinetic properties of insulin analogs may translate into improved clinical efficacy, this has not been convincingly demonstrated in clinical trials, especially for type 2 diabetes. Recent meta-analyses of published clinical trials suggest that, compared with human regular insulin, the rapid-acting analogs provide only a small advantage in terms of A1C reductions, and no advantage for hypoglycemia [6-8]. Compared with human NPH insulin, basal analogs (glargine and detemir) have no advantage for A1C and only minor reductions in nocturnal hypoglycemia [8,9]. Detemir insulin has been shown to cause less weight gain than NPH in clinical trials. The mechanism underlying this effect is unclear.

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