Once bitten twice shy over Degludec

 

At the beginning of the last decade Sanofi Aventis released the first long acting insulin analogue, insulin glargine (Lantus).

It rapidly became a firm favourite with patients, healthcare professionals and share holders alike. It has since gone on to establish itself as the leading long acting analogue and Novo’s subsequent introduction of insulin detemir (Levemir) has done little to dent its popularity.

It would appear that one reason for this has been that many have found Levemir to require twice daily injection. It seems that Novo have been attempting to develop a super long acting analogue ever since.

Several years ago rumours started to emerge that they were working on an insulin that might even just require once weekly injection, this sounded promising! Imagine the clinical applications, young children, the elderly or infirm requiring assistance with their insulin administration, those who are reluctant to inject at all, etc.

Then we learnt its name, it would be called Degludec and would use the same very clever fatty acyl covalent side chain chemistry that the GLP1 agonist liraglutide uses. However, as the months (and years) have gone by, the waiting has dragged on and the promise seems to have diminished.

The original anticipated duration of action seemed over optimistic and perhaps it would be injected every 2-3 days, now, it seems, it will be a once daily insulin. Fair enough, Lantus is a once daily insulin and very good too, and fair enough, Degludec will have a longer half life than Lantus and therefore late injection of a missed dose should be less of a problem.

So, what’s the difference? Well, firstly, Lantus was never more than a once daily insulin and secondly the FDA have now taken a little more of the shine off of Degludec. While the European regulatory authorities have recently approved two Degludec products, known as Tresiba (insulin degludec) and Ryzodeg (insulin degludec/insulin aspart combination), the FDA have deferred final approval pending further cardiovascular safety data.

Apparently a small number of cardiovascular adverse events have been reported in phase 2 and phase 3 trials of Degludec and while the numbers are very small and may, in effect, represent nothing more than a type 1 statistical error, it’s been enough to make the FDA wary.

I suspect the real issue may be the FDA’s previous experience with Rosiglitazone and adverse cardiovascular safety data - “once bitten, twice shy”. Meanwhile, there seems to be just a hint that the promise of Degludec is withering on the vine.

Tags for this article: Insulin

The author - Dr Jeremy Turner

Jeremy Turner A consultant diabetologist and endocrinologist in Norfolk, and author of Diabetes Bible

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