How does Lantus work? Here's how!

I'm new around here, so I don't know how much people want to dialog on this sort of thing. If this kind of thread is not really of interest to people, or has been covered a gazillion times before, let me know!

I'm an engineer by profession, tech toy lover, and general geek (actually, that's Lt. General Geek :-)), hobby scientist, blah blah blah.

So, With just about everything, diabetes included, I always want to know, and am fascinated by how it works.

Some recent discussions on Lantus that I've participated in got me thinking to share some technical details about the stuff that I learned when I first started using it and read through all the research, drug filing, etc. information.

Lantus, like Humalog, Novolog, etc. is an insulin "analog" produced by recombinant DNA (rDNA) techniques. The interesting thing about all these analogs is that they are simply insulin molecules with nothing else special added to the serum, with just one or two changes to the amino acid sequence. These modifications have no impact on the efficacy or potency of the insulin, but do affect the absorption and metabolism of the substance, impacting the duration of action.

Chemically, Lantus (insulin glargine) is a normal human insulin protein modified as follows: "Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the Beta-chain" ref

With these changes the soluability of the molecule in PH neutral fluid decreases substantially, causing precipitate to form. Soluability is restored at an acidic PH of about 4.

This is why Lantus is formulated with an acidic carrier solution -- the drug is completely dissolved, individual proteins (molecules). It's also why it stings for some people.

When Lantus is injected in subcutaneous tissues, the acid is rapidly neutralized, and the modified insulin molecules "clump" together, precipitating out of solution. These crystals/clumps/blobs are way to big to have any effect on cellular insulin receptors, so in this form they are inert.

Gradually, molecule by molecule, these clumps dissolve away. The process is slow because of the relative insoluability of the modified insulin protein. Individual molecules, once freed from a clump, are 100% effective and act just like regular, unmodified human insulin.

The process of slowly breaking these crystals down takes on average about 24 hours, and occurs at a pretty constant rate. This is why Lantus delivers a steady level of active insulin.

Anyone want me to write up something like this for Humalog?

I'm interested. Then again, I LOVED Organic Chemistry, and I find this stuff fascinating. If you're Lt. General Geek, then I'm Commander Geek.

WOW! I always wondered! I would love to hear about Novolog or Humolog! You explained it really well!

I would love the Novo information too! Thanks for the info!

That was very well explained thank you for the write up

Always wondered why it stung more often than other insulin. And… That clumping explanation…explains why occasionally after an injection…you could feel a small bulge or knot just under the skin. I always thought I happy in in a bad spot on my body.

excellent descriptions and fascinating.thank you as well