Insulin analogues long acting

Insulin detemir is a long-acting insulin analogue that lacks threonine at the B30 position and is acylated with a 14-carbon myristoyl fatty acid side-chain at the epsilon-amino group of the lysine in the B28 position. This stimulates binding to albumin and increases the half-life, extending its duration of action. 

Heinemann L, Sinha K, Weyer C, Loftager M, Hirschberger S, Heise T. Time-action profile of the soluble, fatty acid acylated, long-acting insulin analogue NN304. Diabet Med 1999 16(4) 332-8. 

Heinemann L, Linkeschova R, Rave K, Hompesch B, Sedlak M, Heise T. Time-action profile of the long-acting insulin analogue insulin glargine (HOE901) in comparison with those of NPH insulin and placebo. Diabetes Care 2000 23(5) 644-9. 

Long-acting insulin analogues. The more extensive alteration of amino acids in insulin glargine changes the electric charge of the molecule. At pH 4 of the injectate, it is dissolved however, at the pH of tissue it is poorly water-soluble and precipitates. Resolubilization and diffusion into the bloodstream take about one day. 

Insulin analogues Fast acting insulin analogues Long acting insulin analogues... 

Clinical trials on the effects of long-acting insulin analogues showed only a small intraindividual variation of absorption from the injection site with an... 

Jorgensen S, Vaag A, Langkjaer L, et al. (1989). NovoSol basal Pharmaco-kinetics of a novel soluble long-acting insulin analogue. Br. Med. J. 299 415-419. 

Thisted H, Johnsen SP, Rungby J. An update on the long-acting insulin analogue glargine. Basic Clin Pharmacol Toxicol. 2006 99(1) 1-11. 

Intermediate acting isophane insulin (NPH) Long-acting insulin analogues Cloudy 0.5-1.5 h 4-6h 8-16 h... 

Fig. 1. Molecular structures of the long-acting insulin analogues, detemir (upper part) and glargine (lower part).

Treatment with NPH Insulin and the Long-Acting Insulin Analogues... 

Both long-acting insulin analogues - insulin glargine and insulin detemir - have been implemented in the treat to target approach used in type 2 diabetic patients. The analogues are injectable, clear solutions, but the mechanisms by which they achieve prolonged activity differ entirely as described in detail in Chapter 8 and in [11,12]. 

NPH insulin or long-acting insulin analogues at bedtime or mixed short- and long-acting insulin analogues at the main meals 2—3 times a day should be added when HbAj is >7.0% despite maximal dose of OADs. At the start of insulin treatment, obese patients stop the sulphonylurea/meglitinide and the lean patients stop metformin. 

Sarfstein R, Laron Z, Werner H. Long-acting insulin analogues elicit atypical signalling events mediated by the insulin receptor and insulin-like growth factor-I receptor. Diabetologia 2010 53(12) ... 

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