Combining insulin

See also diluting insulin and injecting insulin. For how to agitate, see rolling insulin. For insulins that can't be diluted, see fine doses.

"Combining" insulins refers to mixing them in a single syringe before injecting. BD has animated videos with narrations that show you how to combine two insulins in the same syringe.

It is certainly possible to use insulins "not to be combined" by giving separate injections of them instead. The problem regarding those "not to be combined" in the same syringe has to do with their chemical reactions to each other--not to how they work in the body. Always follow medical advice when using more than one insulin, combined in one syringe or injected separately.

Clear Before Cloudy/Fastest Drawn First

An easy way to remember which insulin is to be drawn first is "clear before cloudy", meaning that the first insulin to draw is always the short-acting clear one. Another memory help is the fastest-acting insulin is to be drawn first. The suspended cloudy one always goes last.

Injecting Air Into Vials

The reason why you are to inject air equal to the unit dose into the cloudy insulin vial first and to draw insulin from it last, is to avoid the possibility of any cloudy insulin going into the short-acting insulin vial. Having this happen could alter the pharmacodynamic properties of the clear, short-acting one. This could "lengthen" the effects of the fast-acting insulin, causing it to behave differently.

Cannot Be Combined-Some Reasons Why

Some insulins, Lantus and Levemir among them, cannot be combined, according to the manufacturers. Both insulins have unique mechanisms of action. Lantus does not form crystals until after it's been injected under the skin. Its pH balance is acid (unlike all other insulins which are pH balanced neutral); the crystal formation occurs when the acid Lantus meets the pH neutral skin. Changing the balance of the insulin can alter the way it performs. Levemir binds to albumin found under the skin and in blood plasma, creating an Insulin depot in the bloodstream--not subcutaneously, as all other intermediate and long acting insulins do. Changing the insulin balance here can also result in changes in its action. Protamine Zinc PZI insulin cannot be combined with other insulins, due to the amount of protamine in the insulin's formula. Others which are not to be combined are any of the Lente family: semilente, Lente, Ultralente and NPH/isophane insulins. The phenol preservatives present in NPH-type insulins alters the Lente-types to the point where they become a close approximation of R/neutral, with regard to action. Keeping the phenol preservatives in mind, all protamine-suspended insulin mixes would be "off limits" regarding same syringe mixing with any Lente-type insulins. PZI and NPH/isophane insulins use a phosphate buffer, where Lente-types have an acetate one. Phosphates alter the profile of Lente-type insulins, making them about as fast-acting as R/Neutral. Animal (Bovine, Porcine) insulins should NOT be mixed in the same syringe with r-DNA or analog insulins.

Insulin glargine (lantus) mechanism of action.

Insulin manufacturers indicate that R/neutral and semilente, Lente, ultralente insulins are able to be combined in the same syringe, but only just before injection. In pre-filled syringes, the zinc suspension of the Lente-type insulins binds the R/neutral, causing it to lose its short-acting effect. Various studies have documented this, and some doctors advise against using R/neutral in the same syringe with the Lente family of insulins.

Further Reading

Insulins-Pharmacokinetic Data & Mixing Information