Insulin types - Insulin Workshop 2021

Insulin Types
By Dr. Usama Ragab Youssif
In light of Insulin Workshop - 3rd Annual ISMA Conference 2021

It includes Insulin history, insulin types, insulin action

1. Insulin Types Usama Ragab Youssif , MD Consultant Internal Medicine Lecturer of Medicine Zagazig University Email: [email protected] Slideshare : https://www.slideshare.net/dr4spring/ Mobile: [phone] rd Annual-ISMA 2021 – Tolip Elforsan Hotel – Ismailia Wednesday 31 st March 2021 – Injectable Antidiabetic workshop

2. History The discovery of insulin was one of the most dramatic and important milestones in medicine - a Nobel Prize-winning moment in science.

3. Paul Langerhans , a medical student in Berlin, discovers a distinct collection of cells within the pancreas. These cells would later be called the Islets of Langerhans . Paul Langerhans had discovered the beta cell 1869 Langerhans, P. (1869). Beitrage zur mikroskopischen Anatomie der Bauchspeicheldruse, Inaugural Disseration.  Gustav Lange .‏ Langerhans , P., & Morrison, H. (1869).  Contributions to the microscopic anatomy of the pancreas . Johns Hopkins Press.‏ ‏

4. In 1889, two German researchers Oskar Minkowski and Joseph von Mering discovered that removing a dog’s pancreas would provoke severe symptoms of diabetes. Pancrease is essential for LIFE 1889 Karamanou , M., et al. (2016). Milestones in the history of diabetes mellitus: The main contributors.  World journal of diabetes ,  7 (1), 1.‏

5. Romanian professor Nicolae Paulescu develops an extract of the pancreas and shows that it lowers blood sugar in diabetic dogs. First trial in animals 1916 Karamitsos , D. T. (2011). The story of insulin discovery.  Diabetes research and clinical practice ,  93 , S2-S8.‏

6. The Discovery 1922 Frederick Banting  had the idea that began the discovery process. He performed the surgeries on the dogs. The discovery of insulin was the highlight of his career. Charles Best , a young biochemistry student, assisted B​anting. 

7. The Discovery

8. The Discovery 1922

9. The first human with diabetes to receive insulin was Joseph Gilchrist . First Patient https://www.nytimes.com/1982/09/14/science/the-tumultuous-discovery-of-insulin-finally-hidden-story-is-told.html

10. The first injection of insulin was given to fourteen-year-old Leonard Thompson , who had been diagnosed in 1919. First Patient Jan 1922

11. Other Patients

12. Thanks Banting

13. Banting and Best improve their techniques for the production of insulin and Eli Lilly becomes the first insulin manufacturer. Nobel Prize

14. NPH Danish physician Hans Christian Hagedorn discovers the action of insulin can be prolonged with the addition of protamine (1936). NPH, an intermediate acting insulin, is marketed by Danish pharmaceutical company Novo Nordisk (1950).

15. Insulin is sequenced by British biochemist Frederick Sanger , and is the first protein to be fully sequenced. In 1958 Sanger receives the Nobel Prize in Chemistry for his research. Another Nobel Prize

16. Different Forms of Insulin The available Insulin nowadays 1- Human Insulin. 2- Insulin Analogues. 3- Biosimilars .

17. Serum Insulin Level Time Analogue Bolus Human Basal Analogue Basal Human Bolus guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca

18. Human Insulin Short Acting Insulin Regular Insulin Premixed Insulin NPH/Regular insulin Intermediate Acting NPH

19. Actrapid

20. Humulin R

21. Egypt

22. NPH Insulins

23. Insulin Mixtard 30

24. Humulin 70/30

25. Egypt

26. Different Forms of Insulin 1- Human Insulin. 2- Insulin Analogues. 3- Biosimilars .

27. Serum Insulin Level Time Analogue Bolus Human Basal Analogue Basal Human Bolus guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca

28. What We Know…

29. Insulin Analogues Rapid Acting Analogues 1- Insulin lispro ( Humalog ) 2- Insulin aspart ( Novolog / Novorapid ) 3- Insulin glulisine ( Apidra ) Long Acting Analogues 1- Insulin glargine ( Lantus / Toujeo ) 2- Insulin detemir ( Levemir ) 3- Insulin degludec ( Tresiba ) Premixed Analogues 1- Insulin lispro / lispro protamine ( Humalog mix) 2- Insulin aspart / aspart protamine ( Novomix ) 3- Insulin Lispro/ degludec ( Ryzodeg ) = coformulation

30. Mane, Krishnappa , et al. "Review of insulin and its analogues in diabetes mellitus."  Journal of basic and clinical pharmacy  3.2 (2012): 283.‏

31. ASP Mane, Krishnappa , et al. "Review of insulin and its analogues in diabetes mellitus."  Journal of basic and clinical pharmacy  3.2 (2012): 283.‏

32. F ast I nsulin Asp art

33. Lys Glu Mane, Krishnappa , et al. "Review of insulin and its analogues in diabetes mellitus."  Journal of basic and clinical pharmacy  3.2 (2012): 283.‏

34. Insulin Analogues Rapid Acting Analogues 1- Insulin lispro ( Humalog ) 2- Insulin aspart ( Novolog / Novorapid ) 3- Insulin glulisine ( Apidra ) Long Acting Analogues 1- Insulin glargine ( Lantus / Toujeo ) 2- Insulin detemir ( Levemir ) 3- Insulin degludec ( Tresiba ) Premixed Analogues 1- Insulin lispro / lispro protamine ( Humalog mix) 2- Insulin aspart / aspart protamine ( Novomix ) 3- Insulin Lispro / degludec ( Ryzodeg )

35. Premixed Analogues Premixed Human

36. Insulin Analogues Rapid Acting Analogues 1- Insulin lispro ( Humalog ) 2- Insulin aspart ( Novolog / Novorapid ) 3- Insulin glulisine ( Apidra ) Long Acting Analogues 1- Insulin glargine ( Lantus / Toujeo ) 2- Insulin detemir ( Levemir ) 3- Insulin degludec ( Tresiba ) Premixed Analogues 1- Insulin lispro / lispro protamine ( Humalog mix) 2- Insulin aspart / aspart protamine ( Novomix ) 3- Insulin Lispro / degludec ( Ryzodeg )

37. Gly Arg Arg Mane, Krishnappa , et al. "Review of insulin and its analogues in diabetes mellitus."  Journal of basic and clinical pharmacy  3.2 (2012): 283.‏

38. Glargine-100 vs. Glargine-300

39. C14 Mane, Krishnappa , et al. "Review of insulin and its analogues in diabetes mellitus."  Journal of basic and clinical pharmacy  3.2 (2012): 283.‏

40. Mane, Krishnappa , et al. "Review of insulin and its analogues in diabetes mellitus."  Journal of basic and clinical pharmacy  3.2 (2012): 283.‏

41. The Co-formulation

42. AA position Human Lispro Aspart Glulisine Glargine Detemir Degludec A21 Asparagine Glycine B3 Asparagine Lysine B28 Proline Lysine Aspartate B29 Lysine Proline Glutamate C14 FA Hexadecandioyl FA B30 Threonine Removed Removed B31 --- Arginine B32 --- Arginine

43. Insulin Biosimilars Currently 2 are available Basaglar (Lilly), a follow-on to insulin glargine (Lantus, Sanofi) approved in 2015 Admelog (Sanofi), a follow-on to insulin lispro (Humalog, Lilly) approved in 2017.

44. Types of insulin Insulin type (trade name) Onset Peak Duration BOLUS (prandial or mealtime) insulins Rapid-acting insulin analogues (clear) Insulin aspart (NovoRapid®) Insulin glulisine (Apidra®) Insulin lispro (Humalog®) U-100 U-200 Faster-acting insulin aspart (Fiasp®) 9–20min 10–15min 10–15min 4min 1–1.5h 1–1.5h 1–2h 0.5-1.5h 3–5h 3.5–5h 3–4.75h 3-5h Short-acting insulins (clear) Insulin regular (Humulin®-R, Novolin® ge Toronto) Insulin regular U-500 ( Entuzity ® (U-500) 30min 15min 2–3h 4-8h 6.5h 17-24h BASAL insulins Intermediate-acting (cloudy) Insulin neutral protamine Hagedorn (Humulin® N, Novolin® ge NPH) 1–3h 5–8h Up to 18h Long-acting insulin (clear) Insulin detemir (Levemir®) Insulin glargine U-100 (Lantus®) Insulin glargine U-300 (Toujeo®) Insulin glargine biosimilar (Basaglar®) Insulin degludec U-100, U-200 (Tresiba®) 90min Not applicable U-100 glargine 24h, detemir 16–24h U-300 glargine >30h degludec 42h PREMIXED insulins Premixed regular insulin –NPH (cloudy) Humulin® 30/70 Novolin® ge 30/70, 40/60, 50/50 A single vial or cartridge contains a fixed ratio of insulin (% of rapid-acting or short-acting insulin to % of intermediate-acting insulin) Premixed insulin analogues (cloudy) Biphasic insulin aspart ( NovoMix ® 30) Insulin lispro/lispro protamine (Humalog® Mix25 and Mix50)

45. Biosimilars

46. We still waiting

47. Final Bottom line Insulin is essential for life Insulin has changed the practice of diabetes since it’s introduction in 1922. Insulin has a wide metabolic activities. Insulin has different preparation, you can use them in different ways according to profile of your patient (One Size Doesn’t Fit All). Biosimilars are coming. Thanks Banting for Insulin.

48. I just adore Toronto and Dr. Banting ! ​            -Elizabeth Hughes “one of the first patients of Banting ”, letter to her mother, 1922 Thanks Cooper T, Ainsberg A. Breakthrough: Elizabeth Hughes, the Discovery of Insulin, and the Making of a Medical Miracle. New York: St Martin’s Press; 2010.