Canine Diabetes Wiki

Humulin U

Ultralente [1] insulin crystals are large and slowly absorbed because of their size, making this a long-acting insulin. [2] At one time, this type of insulin was also produced in bovine, porcine and mixed bovine-porcine forms. The two who most recently took their last bows are of r-DNA/GE/GM origin.

Ultralente is not used very successfully in dogs, but has been widely used in treatment of cats.


Novo Nordisk Ultratard HM-GE Human Ultralente insulin.

Human ultralente insulin was not very reliable when used with many people, either. This is why it wasn't widely used enough to remain on either Eli Lilly's or Novo Nordisk's product list. [3] There's great variability from patient to patient with this insulin. [4] Conclusion in this abstract is it has far too much day-to-day variability to be truly useful for many.

Some people absorb r-DNA ultralente at a faster than usual rate, so for them it would have only the duration of an intermediate acting insulin. [5]. One injection of Bovine Ultralente insulin can last up to 40 hours when administered to a human--longer than Lantus; it is also peakless. [6][7][8] The human duration with Bovine ultralente is due, in part, to the 3 amino acid differences between bovine and human insulin.

Most humans not using an analog intermediate or long acting insulin for basal needs are or were using either NPH or Lente on an average of twice a day.

Specifications of ultralente

British National Formulary defines Ultralente-type insulins as: A sterile neutral (neutral used here refers to the pH, not to the fast-acting insulin known as neutral or R) suspension of bovine insulin or of human insulin in the form of a complex obtained by the addition of a suitable zinc salt; consists of rhombohedral crystals (10-40 microns).

British Pharmacoepia (BP) and United States Pharmacoepia (USP)'s definitions of ultralente insulin: [9]

Insulin zinc suspension (crystalline) BP

Sterile buffered suspension of bovine insulin to which zinc chloride is added. Crystalline form is insoluble in water. Prepared from crystalline insulin containing not more than 23 units/mg. White or almost colourless suspension. Particles are mainly crystalline. Majority of crystals having a maximum diameter greater than 10 m.pH 6.9 - 7.5 Iso-osmotic with blood. Preparation contains 40 and 80 units/ml.

(Note--the BP definition should actually read "mammalian", not "bovine". Novo Nordisk's Ultratard and Eli Lilly's Humulin Zn were both r-DNA/GE/GM insulins. Both were available until recently. Both were also U100 strength, so this strength should have been added above.)

U.S.P. - Sterile suspension of insulin contain 40, 80, 100 units/ml. Contains sodium acetate, sodium chloride and methyl hydroxybenzoate (Concentration same as for amorphous insulin) and zinc 120 - 250 ug. pH 7.2 - 7.5.

What Ultralente Is Not


Human time activity profile for r-DNA/GE/GM ultralente insulin.

No Lente-type insulin regardless of species can contain any NPH/isophane insulin [10] or any R/Neutral insulin. [11][12]

Both are chemically impossible: the phenol preservative present in NPH/isophane alters the action of Lente-type insulins, creating a mixture with an approximate action of R/Neutral. [13][14]

The zinc suspension of Lente-type insulin binds R/Neutral, causing the short-acting insulin to slow, losing its short-acting effect. [15][16]

Before the invention of VetPen, Lente-type insulins could not be dispensed in pen or cartridge form because the glass ball formerly used to mix the insulin in these devices shattered the Lente crystals.[17]

Combining Lente Family Insulins

None of the Lente family of insulins (semilente, Lente, Ultralente) can be combined with [18] 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. [19][20]

Keeping the phenol preservatives in mind, all protamine-suspended insulin mixes would be "off limits" regarding same syringe mixing with any Lente-type insulins. [20]

Insulin manufacturers [21] indicate that R/neutral and semilente, Lente, and 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. [12][22][23][20]

Trade names:


  1. Definition of Ultralente Insulin. Merck Manual.
  2. Dumitriu, Severian (2001). Polymeric Biomaterials, Revised and Expanded 1104. CRC Press.
  3. Discussion of differences between r-DNA Ultralente insulin and beef Ultralente. Free Patents Online.
  4. Lindström T, Olsson PO, Arnqvist HJ. (2000). Use of Human Ultralente Limited By Great Intraindividual Variability. Scandanavian Journal of Clinical/Laboratory Investigations.
  5. Diabetes Forecast-page 2. American Diabetes Association (2006-Page 2).
  6. R A Rizza, P C O'Brien and F J Service (1986). Use of Beef Ultralente for Basal Insulin Delivery. Diabetes Care-American Diabetes Association.
  7. Selam JL, Turner D, Woertz L, Eichner HL, Lauritano A, Charles MA. (1989). Comparison of the Safety and Effectiveness of Human and Bovine Long-acting Insulins. Diabetes Research.
  8. Discussion of differences between r-DNA Ultralente and beef Ultralente insulins. Free Patents Online.
  9. British Pharmacoepia (BP) and United States Pharmacoepia (USP) Definitions of Ultralente Insulin. InChem.
  10. Combining Lente-type Insulins with Phenol-Preserved Insulins. National Federation for the Blind.
  11. Lente Zinc Suspension Causes Loss Of R/Neutral Short-Acting Effect.
  12. 12.0 12.1 Huffman DM, Garber AJ. (1991). Availability of Soluble (R/Neutral) Insulin in Mixed Preparations With Crystalline (Lente) & Ultralente GE Insulin. Clinical Therapeutics. Cite error: Invalid <ref> tag; name "Huffman" defined multiple times with different content
  13. Lente-Type Insulins & NPH/Isophane Insulins-A Bad Combination. National Federation for the Blind.
  14. Havlik I, Galasko G, Alberts E, Furman KI, Seftel HC. (1988). Solubility Changes on Mixing Short- and Long-acting Insulin Preparations. South African Medical Journal.
  15. Deckert, T. (1980). Intermediate-Acting Insulin Preparations: NPH (Isophane) & Lente. Diabetes Care.
    Note--in 1980, there were no r-DNA/GE/GM insulins
  16. Resource Guide. American Diabetes Association (2005).
  17. Hanas, Ragnar (1999). Insulin-Dependent Diabetes-Page 10. ChildrenWithDiabetes.
  18. Phenol Preservatives & Lente-type Insulins--A Bad Combination. National Federation for the Blind.
  19. Lente-Type Insulins & NPH/Isophane Insulins-A Bad Combination. National Federation for the Blind.
  20. 20.0 20.1 20.2 Insulin Therapy-Mixing Precautions. Cite error: Invalid <ref> tag; name "Rx" defined multiple times with different content
  21. Insulin Producers vs Doctors Re:Combining R/Neutral & Lente-type Insulins.
  22. 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.
  23. 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.
  24. Discussion of differences between r-DNA Ultralente and beef Ultralente. Free Patents Online.
  25. Insulin Preparations-UK (1976).

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