Canine Diabetes Wiki

See also diluting insulin and injecting insulin. For how to agitate, see resuspending insulin.

"Combining" insulins refers to mixing them in a single syringe before injecting. BD has animated videos [1] 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.

For a step by step guide on drawing two insulins in the same syringe, see Combining insulin tutorial.

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.

Drawing insulin from the cloudy or slower-acting vial 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. [2] This could "lengthen" the effects of the fast-acting insulin, causing it to behave differently. Reversing these steps (drawing the clear or faster-acting insulin first) can have the same effect. [3]

Injecting Air Into Vials[]

The reason why you are to inject air equal to the unit doses into the insulin vials first is to maintain air pressure equilibrium in the vials when you are ready to draw from them.

Cannot Be Combined-Some Reasons Why[]


Insulin glargine (Lantus) mechanism of action.

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. [4]
  • Levemir binds to albumin found under the skin and in blood plasma, [5][6] creating an Insulin Depot in the bloodstream--not subcutaneously, [7] as all other intermediate and long acting insulins do. Changing the insulin balance here can also result in changes in its action. [8]
  • Protamine Zinc PZI [9] insulin cannot be combined with other insulins, due to the amount of protamine in the insulin's formula. [10][11]

Insulin manufacturers [15] 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. [16][17][18][19][20] I16


  1. Animated Video--Combining Two Insulins in Same Syringe. BD Diabetes.
  2. Alteration of Activity Profiles.
  3. Insulin Therapy. Pediatric Oncall.
  4. Lantus Prescribing Information. Sanofi-Aventis.
  5. Insulin Detemir. USCD Medical Center.
  6. The mechanism of protraction of insulin detemir. Novo Nordisk (2004).
  7. Insulin Detemir. Pharmacy Times.
  8. Levemir Prescribing Information. Novo Nordisk.
  9. Excess Protamine in Protamine Zinc Insulin Formula-Auburn University
  10. Harrower AD, Duncan LJ, Clarke BF. (1975). Comparison of Injection Techniques for Soluble and Protamine Zinc Insulins in Diabetes Mellitus. Practitioner.
  11. Protamine Zinc Insulin (PZI) Binds to Soluble Insulin in Same Syringe. NHS.
  12. Phenol Preservatives & Lente-type Insulins--A Bad Combination. National Federation for the Blind.
  13. DeRuiter, Jack. Insulin Preparations-Lente Insulins. Auburn University.
  14. Parenteral Drug Therapy Manual. Vancouver General Hospital.
  15. Insulin Producers vs Doctors Re:Combining R/Neutral & Lente-type Insulins.
  16. Huffman DM, Garber AJ. (1991). Availability of Soluble (R/Neutral) Insulin in Mixed Preparations of Crystalline (Lente) & Ultralente GE Insulins. Clinical Therapeutics.
  17. Bilo HJ, Heine RJ, Sikkenk AC, van der Meer J, van der Veen EA. (1987). Absorption Kinetics & Action Profiles-Single Subcutaneous Administration of Human Soluble (R/Neutral) & Lente Insulin. Diabetes Care.
  18. Heine RJ, Sikkenk AC, Eizenga WH, van der Veen EA. (1983). Delayed Onset of Action of Soluble (R/Neutral) Insulin After Premixing With Lente Insulin. Diabetes Research & Clinical Practice.
  19. Resource Guide. American Diabetes Association (2005).
  20. Insulin Therapy-Mixing Precautions.

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