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What is Insulin Detemir?
1, A new short acting insulin with no peak similar to
Humalog
2. A new long acting insulin with no peak
3. An intermediate acting insulin similar to NPH
4. An inhaled insulin
5. A Oral insulin
6. A buccal insulin
Two long-acting insulin analogs have been developed for use as "basal"
components of insulin treatment regimens: glargine and detemir. (Insulin
glargine has US Food and Drug Administration [FDA] approval and is marketed
under the trade name Lantus. Insulin detemir has received an "Approvable
Letter" from the FDA indicating that the agency wants some final
issues resolved before granting final approval.)
Insulin glargine has a lower isoelectric point than human insulin,
leading to precipitation at the injection site. Insulin detemir has
a fatty acid side chain that allows albumin binding, primarily resulting
in association with tissue-bound albumin at the injection sites. Both
of these analogs lead to prolongation of action. There also is evidence
of greater reproducibility of effect compared with older insulin preparations,
which is of particular benefit in decreasing the frequency of nocturnal
hypoglycemia after administration at bedtime. Insulin glargine has received
wide recognition as being of benefit in the treatment of both type 1
and type 2 diabetes, with duration of action approximating 24 hours
in most persons. When comparing glargine, NPH, ultralente, and continuous
subcutaneous insulin infusion (CSII), NPH shows an early peak of action;
ultralente also has a peak, although broader; and CSII and glargine
show flat and prolonged curves of insulin action.
It should be noted that the data for use of insulin glargine at bedtime
rather than before dinner or at other points are not compelling. Furthermore,
the mean durations of action of insulins detemir and glargine are 14
and 22 hours, respectively, so that administration twice daily is advisable
for a substantial number of persons with type 1 diabetes given the latter
agent. This may be particularly important in patients with type 1 diabetes
treated with rapid-acting insulin analogs without regular insulin at
dinner. With insulin detemir, administration twice daily is definitely
required for persons with type 1 diabetes. The analog does show "peakless"
action, and studies comparing NPH with insulin detemir in patients with
type 1 diabetes show greater variability of fasting glucose and a 28%
to 34% higher frequency of nocturnal hypoglycemia with NPH than with
the analog.[1,2]
A study presented at the 18th International Diabetes Federation Congress
in Paris in August 2003 reported that among 54 persons with type 1 diabetes
given NPH, detemir, or glargine insulin on 4 occasions with glucose
infused to maintain euglycemia, the coefficient of variation of the
glucose infusion was 46% to 68%, 23% to 27%, and 36% to 48%, respectively,
suggesting that the degree of within-subject variability was least with
detemir.[3] In 505 persons with type 2 diabetes treated with insulin
detemir vs NPH for 6 months, fasting glucose was similar at 175 vs 173
mg/dL, with lower within-persons variability of 23 mg/dL vs 25 mg/dL,
and lesser weight gain of 0.9 vs 1.6 kg. However, A1C showed significantly
greater decrease with NPH in this study (0.26% with detemir vs 0.36%
with NPH).[4]
Still uncertain is whether rapid-acting insulin analogs can be mixed
with insulin detemir for coadministration. If possible, this might decrease
the number of injections required in combination regimens from 5 (2
doses of detemir and 3 doses of insulin aspart or lispro) to 3 (2 doses
of detemir mixed with insulin aspart or lispro before breakfast and
dinner, and a third dose before lunch of the rapid-acting insulin alone).
References
1. Hermansen K, Madsbad S, Perrild H, Kristensen A, Axelsen M. Comparison
of the soluble basal insulin analog insulin detemir with NPH insulin:
A randomized open crossover trial in type 1 diabetic subjects on basal-bolus
therapy. Diabetes Care. 2001;24:296-301. Abstract
2. Vague P, Selam JL, Skeie S, et al. Insulin detemir is associated
with more predictable glycemic control and reduced risk of hypoglycemia
than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen
with premeal insulin aspart. Diabetes Care. 2003;26:590-596. Abstract
3. Heise T, Nosek L, Draeger E, Bilimann Ronn B, Kaptiza C, Heinemann
L. Lower within-subject variability of insulin detemir compared to NPH
insulin and insulin glargine in subjects with type 1 diabetes. Program
and abstracts of the 18th International Diabetes Federation Congress;
August 25-29, 2003; Paris, France. Abstract 12.
4. Gerich J, Bolli G, Becker RHA, Zhu R. Evaluation of serum insulin
levels after single and multiple dosing of insulin glargine. Program
and abstracts of the 18th International Diabetes Federation Congress;
August 25-29, 2003; Paris, France. Abstract 783.
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