Canis ISSN: 2398-2942

Insulin

Synonym(s): Caninsulin, Vetsulin, ProZinc, Lantus, Levemir

Contributor(s): Vetstream Ltd, Linda Horspool

Introduction

Name

  • Insulin.

Class of drug

  • Polypeptide hormone or analog of polypeptide hormone.

Description

Physical properties

  • Suspension (not for intravenous administration) or clear solution, depending on formulation.
  • Insulin exists as monomers at low concentrations and aggregates into stable dimers at higher concentrations, in aqueous solution at pH 2-8, and into hexamers in the presence of zinc ions. Zinc is used in the formulation of insulin to extend its duration of action.

Storage requirements

  • Should be stored in refrigerator prior to opening.
  • Store refrigerated; some products may be kept at room temperature (<25°C) after first opening.
  • Sterile products - usually should be used for no more than 28 days after first opening, some products may be kept at room temperature (<25°C) for this period.
  • Do not freeze.
  • Protect from light.

Uses

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Indications

  • For the reduction of hyperglycemia and hyperglycemia-associated clinical signs in dogs Diabetes mellitus.
  • Adjunctive therapy in the management of hyperkalemia Hyperkalemia.

Formulations

  • Ultra-rapid, rapid, intermediate and long-acting formulations are available. Ultra-rapid acting insulin analogs (eg insulin aspart) are not used routinely in veterinary species due to the risk of hypoglycemia Hypoglycemia but have been used for intensive treatment of diabetic ketoacidosis Diabetic ketoacidosis after fluid replacement.
  • Regular (soluble, neutral) insulin is a clear, colorless, aqueous solution buffered at neutral pH (7-7.8). It contains human recombinant insulin (100 IU/mL) and zinc, which slows its absorption. It has a rapid (<1 h) onset of action, peak effects 1-4 h after administration and a short duration of action (<8 h) after SC administration. Used under close veterinary supervision where a rapid effect is required (eg in the management of diabetic ketoacidosis).
  • Intermediate and long-acting formulations generally need to be administered twice daily to diabetic dogs to provide adequate glycemic control.
  • Isophane insulin (Humulin N) is an intermediate-acting human recombinant insulin suspension that has an onset of action within 2-4 hours, peak action 4-8 hours after administration, and an intermediate duration of action (12-16 h). Twice daily administration is usually required in dogs. Not approved for use in dogs.
  • Porcine insulin zinc suspension (40 IU/mL, Caninsulin or Vetsulin) is approved for use (40 IU/mL) in dogs and cats. A lente insulin containing a mixture of amorphous zinc (semilente, c. 30%) and long-acting crystalline zinc (ultralente, c. 70%) insulin suspensions to provide rapid onset (<2 h), peak action around 4-8 h after SC administration and duration of activity of 14-24 h in dogs. Twice daily administration is required in most dogs; once daily administration may be appropriate in some dogs (eg up to 25%). First choice insulin in dogs.
  • Neutral protamine Hagedorn (NPH) insulin (100 IU/mL) is an aqueous suspension buffered at pH 6.9-7.5. It contains crystalline zinc human recombinant insulin and the basic (positively charged) poly-arginine peptide protamine to provide a moderately rapid onset (<2 h) of action, peak action at 4-8 h and duration of action of 12-24 h. Interindividual variability is high. Twice daily administration is usually required in dogs. Not approved for use in dogs.
  • Protamine Zinc Insulin (40 IU/mL, ProZinc) contains crystalline zinc insulin and protamine to provide rapid onset (<2 h) and duration of activity 12-16 h. Twice daily administration is required in most dogs. Not approved for use in dogs.
  • Insulin glargine Insulin glargine is a basal analog of human insulin where asparagine at A chain position 21 is replaced with glycine and arginine added to B chain positions 31 and 32. Insulin glargine requires twice daily administration in veterinary species to provide adequate glycemic control. It can be variable in duration of action (8-24 hours) and is not used commonly in dogs
  • Insulin detemir Insulin detemir is a basal analog of human insulin where threonine is omitted from B chain position 30 and a 14 carbon fatty acid chain attached to lysine at B chain position 29. It is more potent than other insulins - a lower dose is required and it should be used with caution, especially in small dogs. Insulin detemir is not approved for use in veterinary species (100 IU/mL).

Administration

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Precautions

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Interactions

with other drugs

Drugs which may antagonize the hypoglycemic effects of insulin Drugs which may increase the effects of insulin

Adverse Reactions

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Further Reading

Publications

Refereed papers

  • Recent references from VetMed Resource and PubMed.
  • DiFazio J & Fletcher D J (2016) Retrospective comparison of early- versus late-insulin therapy regarding effect on time to resolution of diabetic ketosis and ketoacidosis in dogs and cats: 60 cases (2003-2013) J Vet Emerg Crit Care (San Antonio) 26, 108-115 PubMed.
  • Walsh E S, Drobatz K J & Hess R S (2016). Use of intravenous insulin aspart for treatment of naturally occurring diabetic ketoacidosis in dogs J Vet Emerg Crit Care (San Antonio) 26, 101-107 PubMed.
  • Maggiore A D, Nelson R W, Dennis J, Johnson E & Kass P H (2012) Efficacy of protamine zinc recombinant human insulin for controlling hyperglycemia in dogs with diabetes mellitus.J Vet Intern Med 26, 109-115 PubMed Article.
  • Gilor C & Graves T K. (2010) Synthetic insulin analogs and their use in dogs and cats. Vet Clin North Am Small Anim Pract. 40, 297-307 PubMed.
  • Rucinsky R, Cook A, Haley S, Nelson R, Zoran D L & Poundstone M (2010) AAHA Diabetes management guidelines for dogs and cats J Am Anim Hosp Assoc 46, 215-224 PubMed.
  • Fleeman L M, Rand J S & Morton J M (2009) Pharmacokinetics and pharmacodynamics of porcine insulin zinc suspension in eight diabetic dogs Vet Rec 164, 232-237 PubMed.
  • Monroe W E, Laxton D J, Fallon E A, Richter K P, Santen D R, Panciera D L, Towell T L, Williams K A, Hart J R, Hill S, Finkler M R & Shinn J S (2005) Efficacy and safety of a purified porcine insulin zinc suspension for managing diabetes mellitus in dogs J Vet Int Med 19, 675-682 PubMed.
  • Graham P A, McKellar Q A & Nash A S (1997) The pharmacokinetics of a highly purified porcine insulin zinc suspension in dogs with naturally occurring diabetes mellitus. J Small Anim Prac 38, 434-438 PubMed.

Other sources of information

  • Gostelow R (2015) Top 5 maintenance insulins. Clinician’s Brief. November, 53-58 Article.
  • Odunayo A (2014) Management of Potassium Disorders. NAVC Clinician’s Brief March 2014, 69-72 Article.
  • Feldman E C, Nelson R W, Reusch C E, Scott-Moncrieff J C & Behrend E  (2014) Canine and Feline Endocrinology. 4th edn, Elsevier, pp 1-669.  
  • Huang A & Scott-Moncrieff J C (2011) Canine Diabetic Ketoacidosis. Diagnostic Tree. NAVC Clinician’s Brief  Handout.
  • Nelson R W (2010) Canine diabetes mellitus. In: SJ Ettinger S J, Feldman E C, eds. Textbook of Veterinary Internal Medicine. Seventh Edition, Saunders Elsevier, pp 1782-1795.
  • Based on Small Animal Formulary.Tennant, Bryn (1999) 3rd edn. Cheltenham: BSAVA.
  • Caninsulin®/Vetsulin® product information - FDA Freedom of Information Summary , www.caninsulin.com & www.vetsulin.com

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