This document discusses basics of insulin therapy including: - The discovery of insulin in the 1920s and types of insulin including basal, mealtime, premixed, and newer combinations. - Insulin action profiles, indications for insulin use, administration techniques using vials, syringes and pens, and common insulin regimens for type 2 diabetes including once or twice daily basal insulin +/- mealtime insulin or premixed insulin. - Proper storage, mixing, and injection of insulin as well as recommended sites for injection are also reviewed.

1. Basics ofBasics of insulin therapyinsulin therapy
Mohsen Eledrisi, MD, FACP, FACE
Department of Medicine
Hamad Medical Corporation
Doha, Qatar
eledrisi@yahoo.com

2. Banting & Best
The discovery of insulin
1921: Isletin isolated
1922:
1st
human experiment
1923:
Name changed to “Insulin”
Insula (latin) = island

3. Insulin secretion
Polonsky K et al. New Eng J Med 1988;318:1231
10
20
30
50
40
SerumInsulin
mcU/ml
BreakfastBreakfast
Basal insulin
LunchLunch DinnerDinner
Meal insulin

4. Types of InsulinTypes of Insulin
• Basal insulin
• Meal insulin

5. Basal insulin
Intermediate –acting:
NPH (Humulin N®
, Insulatard®
)
Long-acting:
Glargine U-100 (Lantus®
)
Glargine U-300 (Toujeo®
)
Glargine biosimilar (Basaglar®
)
Detemir (Levemir®
)
Degludec (Tresiba®
)

6. NPHInsulin
(Neutral Protamine Hagedorn)
Humulin N®
Insulatard®
Looks cloudy
(Like milk)

7. Insulin Glargine U-100
(Lantus®
)
Looks CLEAR
Like water
- Gray pen
- Vial with purple
top

8. Insulin Glargine U-300
(Toujeo®
)
CLEAR
Like water
White pen with green top

9. Glargine biosimilar
(Basaglar®
, Abasaglar®
)

10. Insulin Detemir
(Levemir®
)

11. Insulin Degludec
(Tresiba®
)
U-100 & U-200

12. Meal InsulinMeal Insulin
• Short-acting:
Regular (Actrapid®
, Humulin R®
, Novolin R®
)
• Rapid-acting: (analogs)
- Lispro (Humalog®
)
- Aspart (Novorapid®
, Novolog®
)
- Glulisine (Apidra®
)
All look clear (like water)

13. Regular insulin
Actrapid ®
Humulin®
R
Novolin®
R

14. Insulin Regular U-500
(Humulin R®
U-500)

15. Insulin Lispro
(Humalog®
)
U-100 & U-200

16. Insulin Aspart
[Novorapid®
]
(Novolog®
in USA)

17. Insulin Glulisine
[Apidra®
]

18. Action Profile of Insulins
0 1 2 53 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Plasma
insulin
levels
Regular
NPH
Hours
Glargine, Degludec
Lispro, Aspart, Glulisine
Detemir
Hirsch I. New Eng J Med 2005;352:174

19. Premixed insulinsPremixed insulins
• NPH/R 70/30
• Aspart 70/30
• Aspart 50/50
• Lispro 75/25
• Lispro 50/50
All premixed insulins look cloudy
(like milk)

20. NPH/R70/30
Mixtard®
30
Contains 70 % NPH + 30 % Regular
Mixtard®
30
Mixtard®
30/70
Contains 70 % NPH + 30 % Regular

21. NPH/R70/30
Humulin®
70/30

22. Lispro 75/25
(Humalog®
25, Humalog Mix 75/25®
)
Contains 75 % Lispro protamine + 25 %
Lispro

23. Lispro 50/50
(Humalog®
50, Humalog Mix 50/50®
)
Contains 50 % Lispro protamine + 50 %
Lispro

24. Insulin Aspart 70/30
(Novomix®
30)
(Novolog®
mix 70/30 in USA)
Contains 70 % Aspart protamine + 30 % Aspart

25. Insulin Aspart 50/50
(Novomix®
50)
Contains 50 % Aspart protamine + 50 % Aspart

26. Combination
Degludec/Aspart
(Ryzodeg®
)

27. Combination
Degludec/Liraglutide
(Xultophy®
)

28. Combination
Glargine/Lixisenatide
(Soliqua®
)

29. Indications for insulinIndications for insulin
• Failure of non-insulin glucose-lowering therapy
• Type 1 DM
• Type of DM is not known
• Pregnancy
• Significant symptomatic hyperglycemia (random ≥ 300 mg)
or A1c ≥ 10
• In-hospital

30. Insulin vialsInsulin vials
• “U-100 “ = every 1 ml has 100 units
• 1 vial has 10 ml = 1000 units
• New bottles should be kept in refrigerator [2-8 C°) [not
freezer] until expiration date
• Opened vials are valid for 4 weeks
• Opened vials can be kept in refrigerator or in room
temperature (15-25 C°)

31. Care of insulin vials
• Do not keep in hot places.
• Do not keep in a freezer.
• Do not leave in sunlight.
• Never use insulin if expired.
• Write the date on the insulin vial on the day you open it
or start keeping it outside the fridge. Throw the insulin
away 4 weeks after opened or since kept out of the
fridge.
• Inspect your insulin before each use. Look for changes
in color or clarity. Look for clumps, solid white particles
or crystals in the bottle or pen. Insulin that is clear should
always be clear and never look cloudy.

32. Insulin syringesInsulin syringes
50 units50 units
(0.5 ml)(0.5 ml)
100 units100 units
(1 ml)(1 ml)

33. 50-units insulin syringe
• Lines arranged in order of 5
(5, 10, 15,….)
• Every line equals one unit of insulin
Example: when injecting 12
units, you draw TWO
lines after line 10
10
15

34. 100-units insulin syringe
• lines arranged in order of 10
(10, 20, 30….)
• Every line equals two units
of insulin
Example: when injecting 12
units, you draw ONE line
after line 10
10
20

35. • There are 2 types of pens:
1) Reusable (cartridges are changed)
-Pen stays
2) Disposable:
- Whole pen is changed
• Keep new disposable pen or cartridges
in refrigerator
• Once pen or cartridge is opened, keep
in room temperature (validity depends on type)
Insulin pens

36. Insulin pen care
• Insulin pens must be stored at room temperature:
Storing your insulin pen in extreme temperatures can lead to
changes in the concentration of the pen's insulin.
• Do not share your insulin pen with anyone: even if you are
changing the needles. Infections (HBV, HIV) happened as
insulin itself can be contaminated
• Do not withdraw insulin from the pen cartridge:
can lead to inaccurate dose measurement the next time the
insulin pen is used for dose delivery. The reason for this is
related to air entering the pen unintentionally, interfering with
the proper mechanics of the pen

37. Insulin pen care
• Do not leave an open needle attached to an insulin pen
It can lead to unintentional air entering into the insulin pen
and
ultimately improper dosing of insulin. It could also lead to
insulin contamination.
• Proper insulin pen mixing:
Every time you use a pen containing NPH or premixed
mixtures . The insulin should look uniformly cloudy or milky
after mixing. If there are clumps floating in the insulin, or
white particles stuck to the bottom or sides of the pen giving
it a frosted look, don't use it.

38. How long is the opened pen or
unopened pen outside the
refrigerator valid for ?
• Aspart, Lispro, Glulisine: 4 weeks
• NPH: 2 weeks
• Glargine: 4 weeks
• Detemir: 6 weeks
• Degludec: 8 weeks
• Aspart 70/30: 2 weeks
• Premixed 70/30, Lispro 75/25, Lispro 50/50: 10 days

39. Sites of Insulin Injection
Abdomen, Arms ,Thighs
** Rotate injection sites

40. What time to give insulin?
NPH:
- At bedtime
- Or usually twice/day (usually mixed with meal insulin)
Glargine/Detemir:
- At bedtime (or AM)
- Some need twice daily
Degludec:
- Once daily (at same time of the day)

41. What time to give insulin?
Regular:
- 30 minutes before meals (once, twice or 3 times/day)
Rapid-acting insulins:
- 5 minutes before meals (once, twice or 3 times/day)
- Can be given immediately after meals

42. What time to give insulin?
Premixed 70/30 (Mixtard®
30 or Humulin®
70/30)
- 30 minutes before meals (once, twice or 3 times/day)
Aspart 70/30, Lispro 75/25, Lispro 50/50:
- 5 minutes before meals (once, twice or 3 times/day)

43. Which insulin to use?
Depends on:
Glucose control
Patient characteristics
Lifestyle
Patient preference

44. Insulin regimens in DM 2
Bedtime
Basal long-acting once/day

45. Insulin regimens in DM 2
Bedtime
Basal intermediate once/day

46. Insulin regimens in DM 2
Bedtime
Basal intermediate twice/day
Breakfast

47. Insulin regimens in DM 2
Lunch Bedtime
1 Basal + 1 Meal
BasalMeal

48. Insulin regimens in DM 2
Lunch Dinner Bedtime
1 Basal + 2 Meals
BasalMeal Meal

49. Insulin regimens in DM 2
Breakfast Lunch Dinner Bedtime
1 Basal + 3 Meals
BasalMealMeal Meal

50. Insulin regimens in DM 2
Breakfast Lunch Dinner
2 Basal + 3 Meals
Meal Basal + mealBasal + meal

51. Insulin regimens in DM 2
Breakfast Dinner
2 Intermediate + 2 Meals

52. Insulin regimens in DM 2
Breakfast Dinner
2 Intermediate + 3 Meals
Lunch

53. Insulin regimens in DM 2
Breakfast Dinner
3 Intermediate + 3 Meals
Lunch

54. Insulin regimens in DM 2
Breakfast Dinner
2 Premixed /day

55. Insulin regimens in DM 2
Breakfast Lunch Dinner
3 Premixed /day