Diabetes in Pets

Humulin Lente carton

The lente types of Semilente, Lente and Ultralente are also called zinc suspension insulins.

Technical details[]

Lente insulin is actually a combination of two other lente-type insulins in the fractions 30% semilente insulin and 70% Ultralente insulin. And so the short-acting semilente and the slow-acting ultralente combined produce an insulin that is intermediate-acting[1].

When reading a description of Lente insulin, the word amorphous[2] is often used; the description is often used interchangably with the semilente term, in speaking of the 30% fraction of Lente that is semilente insulin. The word crystalline is also used in connection with describing the composition of Lente insulins; this is the Ultralente 70% fraction.

In cats, Lente has an onset of 0.5-3 hours and a duration of 6-12 hours, so it is a twice-daily insulin[3].

What Lente Is Not[]

No Lente-type insulin regardless of species can contain any NPH/isophane insulin[4] or any R/Neutral insulin[5][6].

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.

The zinc suspension of Lente-type insulin binds R/Neutral, causing the short-acting insulin to slow, losing its short-acting effect[7][8].

Lente-type insulins cannot be dispensed in pen or cartridge form because the glass ball used to mix the insulin in these devices will shatter the Lente crystals[9].

Combining Lente Family Insulins[]

None of the Lente family of insulins (semilente, Lente, Ultralente) can be combined with[10] 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[11].

Keeping the phenol preservatives in mind, all protamine-suspended insulin mixes would be "off limits" regarding same syringe mixing with any Lente-type insulins[12].

Insulin manufacturers[13] 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[14][15][16].

Lente-family members[]

The following insulins are classed as Lente-family insulins, a subset of intermediate-acting insulins with a particular combination of ultralente and semilente. The entire Lente family includes Ultralente, a Long-acting insulin and Semilente, a Short-acting one.

Trade names:

Semilente Insulins

Short acting


Novo Semilente MC

Lente Insulins

Intermediate acting


Hypurin Bovine Lente


Iletin I Lente
(No longer produced.)[17]


Monotard Pork
(No longer produced.)


Iletin II Lente
(No longer produced.)[18]


Monotard, Novolin L
(No longer produced.)


Humulin L
(No longer produced.)

The following are lente type zinc suspension insulins but since they are produced for use in animals, they are not found in BNF, but in its sister veterinary formulary.

Lente Insulins

Intermediate acting


Insuvet Lente


Caninsulin, Vetsulin


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

These fall into the category of intermediate-length insulins.

British National Formulary[19] 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).

Trade names:

Ultralente Insulins

Long acting


Humulin U, Humulin Zn
(No longer produced.)


Novolin U, Ultratard
(No longer produced.)

These fall into the category of long-acting insulins.

Specifications of lente insulins[]


Novo Nordisk Monotard HM--GE Human Lente Insulin.

British National Formulary[20]defines a lente insulin as: A sterile neutral(neutral used here refers to pH, not to the type of insulin known as neutral or R) suspension of bovine and/or porcine 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) and of particles of no uniform shape (not exceeding 2 microns).


Novolin L--Novo Nordisk's GE Lente insulin was sold in North America under this brand name until the end of 2003.

British Pharmacoepia:[21]

Sterile buffered suspension of mammalian insulin in the form of a complex obtained by addition of zinc chloride. Insulin is in a form insoluble in water. Prepared by mixing 3 volumes of insulin zinc suspension (amorphous) and 7 volumes of insulin zinc suspension (crystalline). Contains 40, 80, or 100 units/ml. White suspension available in multidose containers. pH 6.9 - 7.5. Complies with a test for prolongation of insulin effect.

United States Pharmacoepia (USP)[22], which describes the amorphous (semilente) and crystalline (ultralente) fractions separately:

Specifications of semilente fraction--30%[]

Insulin Zinc Suspension BP (Amorphous)

Sterile buffered suspension of mammalian insulin in the form of a complex obtained by addition of zinc chloride. Prepared from crystalline insulin containing not less than 23 u almost colourless suspension in which the particles have no uniform shape and rarely exceed 2 m in dimension; pH 6.9 - 7.5. Iso-osmotic with blood. Containing suitable bactericide, the preparation contains 40 and 80 units/ml.

(Note: semilente insulin alone has not been available in most markets for many years, thus the lack of notation for U100 strength insulin. It is presently available in porcine form from Polfa Tarchomin in Poland. Novo Nordisk recently discontinued its version of this insulin.)

U.S.P. describes a sterile suspension of insulin U.S.P. in buffered water for injection is modified by addition of zinc chloride so that the solid phase of suspension is amorphous. Contains 40, 80 or 100 units/ml. Also contain sodium acetate 0.15 - 0.17%, sodium chloride 0.65 - 0.75%, methyl hydroxy benzoate 0.09 - 0.11% and for each 100 units of insulin, 120 - 250 g of zinc. pH 7.2-7.5

Specifications of ultralente fraction--70%[]


Iletin II Lente-U100 pork insulin by Lilly. This was discontinued in 2003.

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 be "mammalian", not "bovine" insulin, as r-DNA/GE/GM ultralente insulin was available in the UK until recently; Lilly's Humulin Zn and Ultratard were the brand names. The definition of strength should include U100, as both of the above-mentioned insulins were of U100 strength.)

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.

Further Reading[]




  1. Better Medicine-E-Newsletter-June 2006
  2. Dorlands Medical Dictionary: Definition of Amorphous
  3. Providing Care for Diabetic Veterinary Patients-International Journal of Pharmaceutical Compounding-2000-Page 3
  4. Combining Lente-type Insulins with Phenol-Preserved Insulins
  5. Lente Zinc Suspension Causes Loss Of R/Neutral Short-Acting Effect
  6. Availability of Soluble (R/Neutral) Insulin in Mixed Preparations With Crystalline (Lente) & Ultralente GE Insulin-Clinical Therapeutics-1991
  7. Intermediate-Acting Insulin Preparations: NPH (Isophane) & Lente Diabetes Care-1980
    Note--in 1980, there was only beef Lente-type insulin--no pork or r-DNA/GE/GMLente insulins
  8. Resource Guide 2005-American Diabetes Association
  9. Insulin-Dependent Diabetes--Page 10--Dr. Ragnar Hanas
  10. Phenol Preservatives & Lente-type Insulins--A Bad Combination
  11. RxEd.org-Insulin Therapy-Mixing Precautions
  12. RxEd.org-Insulin Therapy-Mixing Precautions
  13. Insulin Producers vs Doctors Re:Combining R/Neutral & Lente-type Insulins
  14. Availability of Soluble (R/Neutral) Insulin in Mixed Preparations of Crystalline (Lente) & Ultralente GE Insulins-Clinical Therapeutics-1991
  15. Absorption Kinetics & Action Profiles-Single Subcutaneous Administration of Human Soluble (R/Neutral) & Lente Insulin-Diabetes Care-1987
  16. Delayed Onset of Action of Soluble (R/Neutral) Insulin After Premixing With Lente Insulin Diabetes Research & Clinical Practice-1983
  17. Iletin I Lente-Beef/Pork Insulin Shown at Right
  18. Carton Image-Iletin II Lente
  19. British National Formulary-Ultralente Insulin
  20. British National Formulary-Lente Insulin
  21. British Pharmacoepia-Lente Insulin
  22. United States Pharmacoepia (USP)-Lente Insulin USP

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