Mixed

There's a lot to cover in the category of mixed insulins, as they can be animal origin, r-DNA/GE/GM origin or analog insulins. The non-analog mixed insulins are made up of intermediate-acting NPH/isophane insulin and short-acting R/neutral. normal insulin. The analog mixes are made from intermediate-acting protamine-suspended analog insulin (suspended similar to NPH/isophane insulin) and fast-acting analog insulin. They can also vary in the fraction (amount or percent) of the two types (R/neutral and NPH/isophane) of insulin used to make a non-analog mix, and in the percentage of fast/rapid-acting analog insulin and slower-acting protamine suspended analog insulin.

For some reason, those in the US choose to list the slower, NPH/isophane based insulin fraction first, such as Humulin or Novolin 70/30. The rest of the world gives the faster insulin top billing and the result is 30/70 ^[1]. Regardless of how this is written, it means that the insulin is made up of 70% NPH/isophane insulin and 30% R/neutral insulin.

The most common mixes are 70/30 (30/70) (non analog) or 75/25 (25/75) (analog). There are no currently-marketed mixes which combine insulins of different origins. Eli Lilly's form of beef/pork Iletin and Novo Nordisk's Lentard were discontinued some time ago.

For the most part, non-mixed Intermediate-acting insulins are generally used for dogs with diabetes. Here are the most common ones that could cause confusion:

Non-Analog Mixed Insulins
	All Intermediate-acting
Insulin Is	Expressed As	Expressed As
10% R/Neutral Insulin 90% NPH/Isophane Insulin	90/10	10/90
20% R/Neutral Insulin 80% NPH/Isophane Insulin	80/20	20/80
30% R/Neutral Insulin 80% NPH/Isophane Insulin	70/30	30/70
40% R/Neutral Insulin 60% NPH/Isophane Insulin	60/40	40/60
50% R/Neutral Insulin 50% NPH/Isophane Insulin	50/50	50/50

Specifications of mixed insulins[]

British National Formulary ^[2] classes all of them as biphasic ^[3] insulins--having more than one activity or action. Regardless of their origin, the two actions are that of the fast/rapid or short acting insulin in combination with the intermediate-acting isophane or isophane-suspended analog insulin. The activity profiles of the mixed or biphasic insulins vary by whether they are analog or non-analog insulins and the fractions of the faster and slower insulins used in the mix.

Non-analog mixes[]

Non-analog mixed insulins
	All intermediate acting
R-DNA/GE/GM 30% R/Neutral 70% NPH/isophane	Actraphane 30/70, Huminsulin Profil III Humulin 3/7, Humulin 30/70, Humulin 70/30 Humulin M3, Humulin Mix 30/70 Humulina 30/70, Humuline 30/70 Insuman Comb 30, Mixtard 30, Novolin 30R Novolin 70/30, Penmix 30, Profil 30 Umuline Profil 30, Winthrop Comb 30 Humulin ReliOn 70/30
R-DNA/GE/GM	ReliOn/Novolin 70/30 (No longer produced.)
R-DNA/GE/GM 50% R/Neutral 50% NPH/isophane	Actraphane 50/50, Huminsulin 50/50 Humulina 50/50, Humuline 50/50 Insuhuman Comb 50, Insuman Comb 50 Penmix 50, Winthrop Comb 50
R-DNA/GE/GM 50% R/Neutral 50% NPH/isophane	Humulin 50/50, Humulin M5, Mixtard 50 (No longer produced.)
R-DNA/GE/GM 20% R/Neutral 80% NPH/isophane	Actraphane 20/80, Huminsulin Profil II Humulin 20/80, Humulin 80/20, Humulin M Humulina 20/80, Humuline 20/80, Penmix 20 Profil II, Umuline Profil 20
R-DNA/GE/GM 20% R/Neutral 80% NPH/isophane	Humulin 20/80, Humulin M2, Mixtard 20 (No longer produced.)
R-DNA/GE/GM 25% R/Neutral 75% NPH/isophane	Insuhuman Comb 25, Insuman Comb 25 Isuhuman Comb 25, Winthrop Comb 25
R-DNA/GE/GM 15% R/Neutral 85% NPH/isophane	Insuhuman Comb 15, Insuman Comb 15 Winthrop Comb 15
R-DNA/GE/GM 40% R/Neutral 60% NPH/isophane	Actraphane 40/60, Huminsulin Profil IV Humulin 60/40, Humulina 40/60 Humuline 40/60, Penmix 40, Profil 40
R-DNA/GE/GM 40% R/Neutral 60% NPH/isophane	Humulin M4, Humulin 40/60, Mixtard 40 Umuline Profil 40 (No longer produced.)
R-DNA/GE/GM 10% R/Neutral 90% NPH/isophane	Actraphane 10/90, Huminsulin Profil I Humulina 10/90, Humuline 10/90 Penmix 10, Profil I
R-DNA/GE/GM 10% R/Neutral 90% NPH/isophane	Humulin 10/90, Humulin M1, Mixtard 10 (No longer produced.)
Porcine 30% R/Neutral 70% NPH/isophane	Hypurin Porcine 30/70 Mix
Porcine 30% R/Neutral 70% NPH/isophane	Pork Mixtard 30 (No longer produced.)
Bovine/Porcine 25% R/Neutral 75% NPH/isophane	Rapidtard (No longer produced.)

There are other various mixes (all human origin) on the market in other countries; the R/neutral fraction or percentage ranges from 10 to 50. In the US, only 70/30 remains on the market, with a wider range available in other parts of the world.

Why Lente doesn't equal 70/30[]

Let's look at the differences in the two insulins. Lente is comprised of 70 % long-acting Ultralente insulin and 30% short-acting Semilente insulin. So proportions of a long-acting and short-acting insulin are being combined to produce a intermediate-acting insulin. Both Ultralente and Semilente insulin are suspended by adding zinc and the size of their respective insulin crystals. The largest insulin crystals are those of Ultralente, while Semilente contains the smallest, or microcrystals. Simply put, you're combining a long insulin and a short insulin to make an intermediate-acting one.

70/30 insulin starts with 70% NPH/isophane insulin, an intermediate-acting insulin which is suspended by protamine. To that, 30% R/neutral/normal insulin, which is short-acting and soluble, meaning there is no suspension; nothing is added to this insulin to delay its action. In this case, you are taking an intermediate-acting insulin with a suspension and adding to it a short-acting one with no suspension to create an intermediate-acting insulin.

So we have an insulin (Lente), made up of a long-acting and short-acting insulin, both with zinc suspensions, and a mixed insulin (70/30), made from an intermediate-acting protamine suspended insulin and a short-acting one without any suspension. Because of these differences, the insulin action profile for these two insulins is going to be quite different, even though both insulins are classed as intermediate-acting.

Analog mixes[]

These are not as widely varied. The "basics" are that they most commonly come in 70/30 (30/70) or 75/25 (25/75) fractions. Made of either insulin aspart (Novo) or insulin lispro (Lilly), they are a combination of the fast/rapid acting analog insulin and the same analog insulin which has been "slowed down" by a process of creating special crystals of either insulin aspart or insulin lispro with protamine suspension.

The same is true for analog mixed insulins as for non-analog ones regarding the US listing the percentage or fraction of the slower insulin first and everyone else choosing to list the faster action portion that way.

Analog mixed insulins
	All intermediate acting
30% insulin aspart 70% insulin aspart, protamine suspension	Novolog Mix NovoMix 30
25% insulin lispro 75% insulin lispro, protamine suspension	Humalog 75/25 Humalog Mix 25
50% insulin lispro 50% insulin lispro, protamine suspension	Humalog 50/50 Humalog Mix 50

References[]

More Information[]

• Diabetes control in Siberian Husky-Vet Info Richards, Mike, VetInfo4Dogs.
  Details about using mixed non-analog insulins with canine diabetes patient & discussinguse of mixed insulins.
• Insulins & Mixtures-NHS UK
• NACDS-Insulin Chart-Page 2