Evaluating Insulin Glargine Pharmacodynamics by Administration Time

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In patients with type 2 diabetes, the pharmacodynamics of insulin glargine change based on the time of the injection due to circadian changes in insulin sensitivity, according to a study published in Diabetes Care.

Although the pharmacodynamics varied based on time, the pharmacokinetics of insulin glargine was not affected by administration time, reported Francesca Porcellati, MD, of the University of Perugia Medical School in Perugia, Italy, and colleagues.

The study included 10 patients with type 2 diabetes who were treated with insulin. Each patient was studied during a 24-hour euglycemic glucose clamp after glargine injection either in the evening or in the morning.

The 24-hour glucose infusion rate was comparable for evening and morning, but the rate during the first 12 hours was lower with evening injections compared with morning. For the second 12-hour period, the glucose infusion rate was lower with morning injections. Compared with morning injections, evening injections led to a greater suppression of plasma glucagon levels and lipolysis. Plasma insulin and C-peptide levels did not differ with injection time.

The results indicate that the pharmacodynamics of insulin glargine changed based on when the injection is administered. However, because the pharmacodynamics of insulin glargine did not vary when analyzed over a 24-hour period, the changes reflect the impact of circadian changes in insulin sensitivity among patients with type 2 diabetes.

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Evaluating Insulin Glargine Pharmacodynamics by Administration Time

OBJECTIVE To compare pharmacokinetics (PK) and pharmacodynamics (PD) of insulin glargine in type 2 diabetes mellitus (T2DM) after evening versus morning administration.

CONCLUSIONS The PD of insulin glargine differs depending on time of administration. With morning administration insulin activity is greater in the first 0–12 h, while with evening administration the activity is greater in the 12–24 h period following dosing. However, glargine PK and plasma C-peptide levels were similar, as well as glargine PD when analyzed by 24-h clock time independent of the time of administration. Thus, the results reflect the impact of circadian changes in insulin sensitivity in T2DM (lower in the night-early morning vs. afternoon hours) rather than glargine per se.

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