Lente insulin
Lente insulin (from Italian lento, "slow"; also called insulin zinc suspension) was an intermediate duration insulin that is no longer used in humans.[1] The onset of lente insulin is one to two hours after the dose is administered, and the peak effect is approximately 8 to 12 hours after administration, with some effects lasting over 24 hours.[2]
Lente insulin products, along with other insulin analogs in the same family, were discontinued by their manufacturers in the mid-2000s, and are no longer permitted to be marketed for use in humans in the US.[3][4] This was in part because health care providers began to favor more predictable forms of insulin, such as recombinant NPH insulin.[5]
History
Lente insulin arose from research into ways to alter the
In the 1990s,
Veterinary use
After the discontinuation of lente insulin for human use, the FDA approved a veterinary porcine-derived lente insulin (Vetsulin®,
Adverse effects
Hypoglycemia
The primary adverse effect of any insulin product is hypoglycemia, or low blood sugar. Hypoglycemia can manifest as dizziness, disorientation, trouble speaking, and changes in mental status. In severe cases, hypoglycemia can lead to loss of consciousness if not treated.[12] As lente insulin continues to be absorbed in the body for hours after use, these signs and symptoms may be delayed from the time of administration and begin with little or no warning.[citation needed]
Hypersensitivity
Lente insulin is a combination of porcine and bovine insulin products which are filtered and combined with zinc to form the suspension. Even product that is filtered very well is still of animal origin, and there is a chance the body may recognize the foreign protein as such and form antibodies against it. These reactions are slightly more likely with lente insulin than with insulin derived from a single source as lente insulin contains bovine insulin which is more immunogenic than porcine insulin.[7]
Pharmacology
Mechanism of action
Insulin is a protein normally produced in the pancreas which regulates metabolic processes throughout the body. The primary role of insulin is to increase the metabolism of glucose, storage of energy in adipose tissue, and decrease the body's own production of glucose.[13]
Pharmacokinetics
The half life of
Lente insulin was formulated by the addition of zinc to the crude porcine and bovine insulin extracts, which causes the insulin protein to form larger crystals which dissolve into the body slower upon injection.[7] This means that while the insulin in the bloodstream is still metabolized in 4–6 minutes, more insulin is continually being absorbed from the dose injected for hours after administration. Compared to NPH insulin, another intermediate acting insulin, up to 40% of the dose of lente insulin may remain unabsorbed for over 24 hours after administration. The variation in absorption between doses in the same patient of lente insulin is comparable to that of insulin NPH.[7]
The distribution of insulin is not well understood, but it is known that it is heavily
Manufacturing
Commercial preparations of lente insulin are standardized to 30%
Society and culture
Brand names of lente insulin that have been discontinued include Iletin (animal), and HumulinL/NovolinL (human). As of 2023, Lente insulin is produced under the brand name Vetsulin for veterinary use in dogs and cats with diabetes.[10]
References
- ^ Holmberg, Monica (1 October 2006). "An Overview of Insulin Breakthroughs". Pharmacy Times. Vol. 2006, no. 10. Pharmacy & Healthcare Communications. Retrieved 11 May 2020.
- PMID 21668337.
- ^ Federal Register Doc. E9-2901
- ^ Federal Register Doc. 2011-14164
- ^ "Discontinuation of Humulin®U ULTRALENTE" (PDF). Food and Drug Administration. Archived from the original on 1 December 2011. Retrieved 11 May 2020.
{{cite web}}
: CS1 maint: bot: original URL status unknown (link) - PMID 12984132.
- ^ S2CID 22310080.
- PMID 29632581.
- PMID 17443605.
- ^ a b "Compendium of Veterinary Products". merckusa.cvpservice.com.
- ^ S2CID 43327430.
- ^ "Hypoglycemia". National Institute of Diabetes and Digestive and Kidney Diseases. October 2008. Archived from the original on 1 July 2015.
- PMID 21864752.
- ^ PMID 9793760.
- ^ OCLC 52707816.