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Slower Subcutaneous Absorption Of Insulin Glargine Compared To NPH Insulin In Type 2 Diabetics

Insulin glargine has a slower subcutaneous absorption rate compared to NPH insulin in patients with type 2 diabetes, which may help produce a serum insulin profile more similar to that of healthy individuals.

Previous studies have shown that NPH insulin given at bedtime together with oral hypoglycaemic agents can result in good overall glycaemic control. However, the action profile of NPH insulin may result in an inappropriate decrease in blood glucose during early morning hours, and the absorption profile can be highly variable.

Insulin glargine is a long-acting human insulin analogue containing several structural modifications. Studies in healthy volunteers have shown more desirable absorption characteristics for insulin glargine compared to NPH insulin, with little variability in the subcutaneous (s/c) absorption rate.

Stephen D. Luzio, Ph.D., with the Llandough Hospital and Community NHS Trust, Cardiff, United Kingdom, and colleagues performed a study to compare the s/c absorption characteristics of insulin glargine with NPH insulin in patients with Type 2 diabetes using ¹²⁵I-labelled insulins.

Fourteen patients (mean age, 56.3 + 9.4) with type 2 diabetes and no previous insulin treatment were randomised to receive either a single s/c injection of 0.3 U/kb ¹²⁵I-insulin glargine or ¹²⁵I-NPH insulin in a fasting state. The disappearance of radioactivity was monitored for 2.5 days, and the procedure was repeated with the other insulin after a washout period of 7 days.

The median times for 25%, 50%, and 75% of the radioactivity to disappear from the injection site were significantly shorter for NPH insulin compared to insulin glargine (25%, 6.5 and 15.0h, P=0.009; 50%, 13.4 and 26.3h, P=0.009; 75%, 26.6 and 42.4h, P=0.019). In addition, the mean residual radioactivity remaining at 24, 36, and 48 hours was significantly higher for insulin glargine (54.5 and 27.9%, P=0.0001; 35 and 17.0%, P=0.003; 19.2 and 9.2%, P=0.01).

The researchers also found that insulin glargine produces a more delayed decrease in plasma glucose levels compared to NPH insulin. Mean plasma glucose levels reached a minimum after 14.6 + 1.3 and 9 + 2.0 hours in response to insulin glargine and NPH insulin, respectively. A similar trend was observed for serum C-peptide concentrations.

"Subcutaneous insulin glargine is well-tolerated and confirms a much slower absorption over a 24h period compared with NPH insulin," the researchers conclude. "The pharmokinetic profile of insulin glargine should decrease the likelihood of nocturnal hypoglycaemic episodes, thereby improving overall disease management," they suggest.
Horm Metab Res 2003 Jul;35:7:434-438. "Comparison of the Subcutaneous Absorption of Insulin Glargine (Lantus(R)) and NPH Insulin in Patients with Type 2 Diabetes"

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