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NPH Insulin Works Well — If You Mix It Enough

The variability from day to day might alarm you if you manage your diabetes with one of the intermediate acting insulins. The problem could be that you aren’t mixing it well enough.

The type of insulin that we call NPH can take one to three hours to start working. But it lasts for 12 to 16 hours.

Its generic name is NPH; Novo Nordisk sells it as Novolin N and Lilly as Humulin N. NPH is also available premixed with short acting insulin.


But NPH insulin is itself a mixture, and that’s the problem. Its cloudy part is rich in insulin crystals while its clear part isn’t. Before you inject it, you have to mix these parts.

An insulin pen is a convenient way to inject NPH, and a typical recommendation is to “roll and gently shake 10 times” every time you use it.  A study just published online ahead of print in the professional journal Diabetes Care shows that this isn’t good enough.

Only the abstract of his study by eight researchers at Italy’s Perugia University School of Medicine is online. The lead author, Paola Lucidi, M.D., Ph.D., sent me a copy of the full-text.

Using an Insulin Pen

They enrolled a small group of 11 people with type 1 diabetes in a randomized, open-label, crossover design study. For the study they used an insulin pen.

The study looked at the different effect of adequately mixing the insulin the pen compared with just holding it (1) horizontally, (2) vertically with the tip up, or (3) vertically with the tip down without trying to mix it. The differences were “profound,” the researchers wrote. They “may importantly contribute to day-to-day glycemic variability of type 1 diabetes.”

Mix Gently and Long

These are “extreme situations” compared with “the more common condition where patients inject NPH insulin after only partial, incomplete re-suspension,” they wrote. They found that you need to gently tip the pen 20 times during one and one-half minutes before injecting, admitting that this is “quite long for preparation of an insulin injection.” But it is “a key step that some patients might totally or partially skip.”

NPH Properly Mixed Is an Alternative to Long Acting Insulins

This study examined NPH injections only with pens and not with vials, although the study authors “anticipate similar findings.” And it doesn’t apply to long acting insulins like Lantus or Levemir, which more of us use.

But those long acting insulins are expensive, and some of the people who have diabetes can’t afford them. Many people stay with NPH or have switched back to it when the cost of Lantus or Levemir became beyond their means.

The message for anyone who is uses NPH is clear: shake it gently and for a long enough time.

This article is based on an earlier version of my article published by HealthCentral.

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  • Walter at

    “Shake it gently & for a long enough time” is totally useless advice.
    What ever happened to making sure one’s NPH is uniformly suspended before injecting?
    There is no evidence that “gently tipping one’s pen 20 times over 90 seconds” will be sufficient.
    As a T1 for 47 years, I know 897 reasons for day-to-day variability in blood glucose levels.
    Nothing beats frequent blood glucose checks at least 8 times each & every day.