Insulin initiation and optimization in treating type 2 diabetic patients.

1. Insulin Therapy
Initiation and Adjustment
Dr Shahjada Selim
Department of Endocrinology
Bangabandhu Sheikh Mujib Medical University
Email: selimshahjada@gmail.com
1

2. Issues in the Management of
Type 2 Diabetes
• Type 2 DM is a chronic condition with progressive
loss of beta-cell function over time
• Increasing prevalence with obesity
• Hyperglycemia affects morbidity, mortality
• Tight glycemic control with insulin may reduce
costly complications
2

3. 3
• 30% to 40% of patients ultimately require
insulin.
• Newer semisynthetic or analog insulins
and delivery systems may improve
compliance and achieve better glycemic
control with less hypoglycemia.
…………………Conted

4. Defined glycemic targets in T2DM
PG=plasma glucose.
1. American Diabetes Association. Diabetes Care 2005;28(suppl 1):S14—36.
2. American Association of Clinical Endocrinologists. Endocr Pract 2002;8(suppl 1):43—84.
3. International Diabetes Federation. Diabet Med 1999;16:716—30.
*1−2 hours postprandial; **2 hours postprandial.
Glucose control Healthy ADA1
AACE2
IDF3
HbA1c (%) <6 <7 ≤6.5 ≤6.5
Mean FPG
mmol/l (mg/dl)
<5.6
(<100)
5−7.2
(90−130)
<6
(<110)
<6
(<110)
Mean
postprandial PG
mmol/l (mg/dl)
<7.8
(<140)
<10*
(<180)
<7.8**
(<140)
<7.5**
(<135)
4

5. The Goal of Insulin Therapy:The Goal of Insulin Therapy:
Attempt to Mimic Normal Pancreatic Function
Schade, Skyler, Santiago, Rizza, “Intensive Insulin Therapy,” 1993, p. 131.
0
6 0
3 0
1 0 0
6 0
1 4 0
1 5
1 9 3 0
H O U R S
2 3 3 0 0 3 3 0 0 7 3 01 5 3 01 1 3 03 3 0
8 0
4 0
1 2 0
7 5
1 6 0
P L A S M A
G L U C O S E
m g / d l
B L S H S
P L A S M A F R E E
IN S U L IN
u / m l

6. Purpose of Insulin Therapy
• Prevent and treat fasting and postprandial
hyperglycemia
• Permit appropriate utilization of glucose and
other nutrients by peripheral tissues
• Suppress hepatic glucose production
• Prevent acute complications of uncontrolled
diabetes
• Prevent long term complications of chronic
diabetes
6

7. All type 1 diabetics should be on a
Bolus-bolus insulin regimen to
control glucose while minimizing
hypoglycemia.
6-19

8. However over time, most type 2
diabetics will also need both basal
and mealtime insulin to control
glucose.
6-19

9. Initiating Insulin Therapy
6-36

10. Patient Concerns About Insulin
• Fear of injections
• Perceived significance of need for insulin
• Worries that insulin could worsen diabetes
• Concerns about hypoglycemia
• Complexity of regimens
10

11. When to Start Insulin?
• Watch for the following signs
– Increasing BG levels
– Elevated A1C
– Unexplained weight loss
– Traces of ketonuria
– Poor energy level
11
When OHAs are not enough to achieve
target glycemic status --

12. …..When Oral Medications Are Not Enough
– Sleep disturbances
– Polydipsia
• Next steps
– Make a decision to start insulin
– Offer patient encouragement, not blame
12

13. …..Initiating Insulin Therapy in Type 2 Diabetes
• Let blood glucose levels guide choice of
insulins
– Select type(s) of insulin and timing
of injection(s) based on pattern of
patient’s sugar (fasting, lunch,
dinner, bedtime)
13

14. ….Initiating Insulin Therapy in Type 2 Diabetes
Choose from currently available insulin
preparations
• Rapid-acting (mealtime): lispro, aspart,
glulisine
• Short-acting (mealtime): regular insulin
• Intermediate-acting (background): NPH, lente
• Long-acting (background): degledec, detemir,
glargine
• Insulin mixtures (premixed) /coformulations

15. ….Initiating Insulin Therapy in Type 2 Diabetes
• Provide long-acting or intermediate-
acting as basal and rapid-acting as bolus
• Titrate every week
Goal: to approximate endogenous insulin secretion…

16. 16
The ADA Treatment Algorithm forThe ADA Treatment Algorithm for
the Initiation and Adjustment ofthe Initiation and Adjustment of
InsulinInsulin

17. 17
Step One: Initiating InsulinStep One: Initiating Insulin
• Start with either…
–Bedtime long-acting/intermediate acting
insulin
Insulin regimens should be designed taking
lifestyle and meal schedules into account
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

18. 18
Step One: Initiating InsulinStep One: Initiating Insulin, cont’d, cont’d
• Check fasting glucose and increase dose
until in target range
– Target range: 3.89-7.22 mmol/l (70-130 mg/dl)
– Typical dose increase is 2 units every 3 days,
but if fasting glucose >10 mmol/l (>180 mg/dl),
can increase by large increments (e.g., 4 units
every 3 days).
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

19. 19
• If hypoglycemia occurs or if fasting glucose
>3.89 mmol/l (70 mg/dl)…
–Reduce bedtime dose by ≥4 units or 10%
if dose >60 units
Step One: Initiating InsulinStep One: Initiating Insulin, cont’d, cont’d
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

20. 20
• If HbA1c is <7%...
– Continue regimen and check HbA1c every
3 months
• If HbA1c is ≥7%...
– Move to Step Two…
After 2-3 Months…After 2-3 Months…
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

21. 21
Initiating and Adjusting InsulinInitiating and Adjusting Insulin
Continue regimen; check
HbA1c every 3 months
If fasting BG in target range, check BG before lunch, dinner, and bed.
Depending on BG results, add second injection
(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)
Recheck pre-meal BG levels and if out of range, may need to add another
injection; if HbA1c continues to be out of range, check 2-hr postprandial levels
and adjust preprandial rapid-acting insulin
If HbA1c ≤7%...
Bedtime intermediate-acting insulin, or
bedtime or morning long-acting insulin
(initiate with 10 units or 0.2 units per kg)
Check FG and increase dose until in target range.
If HbA1c ≥7%...
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
Pre-bed BG out of range: add
rapid-acting insulin at dinner
Continue regimen; check
HbA1c every 3 months
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
If HbA1c ≤7%... If HbA1c ≥7%...

22. 22
Step One…
Continue regimen; check
HbA1c every 3 months
If fasting BG in target range, check BG before lunch, dinner, and bed.
Depending on BG results, add second injection
(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)
Recheck pre-meal BG levels and if out of range, may need to add another
injection; if HbA1c continues to be out of range, check 2-hr postprandial levels
and adjust preprandial rapid-acting insulin
If HbA1c ≤7%...
Bedtime long-acting insulin
(initiate with 10 units or 0.2 units per kg)
Check FG and increase dose until in target range.
If HbA1c ≥7%...
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
Pre-bed BG out of range: add
rapid-acting insulin at dinner
Continue regimen; check
HbA1c every 3 months
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c ≤7%... If HbA1c ≥7%...
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

23. 23
Step Two: Intensifying InsulinStep Two: Intensifying Insulin
If fasting blood glucose levels are in target
range but HbA1c ≥7%, check blood glucose
before lunch, dinner, and bed and add a
second injection:
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

24. 24
Step Two: Intensifying InsulinStep Two: Intensifying Insulin
• If pre-lunch blood glucose is out of range,
add rapid-acting insulin at breakfast
• If pre-dinner blood glucose is out of range,
add NPH insulin at breakfast or rapid-
acting insulin at lunch
• If pre-bed blood glucose is out of range, add
rapid-acting insulin at dinner
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

25. 25
Insulin AdjustmentsInsulin Adjustments
• Can usually begin with ~4 units and
adjust by 2 units every 3 days until
blood glucose is in range.
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

26. 26
• If HbA1c is <7%...
–Continue regimen and check HbA1c
every 3 months
• If HbA1c is ≥7%...
–Move to Step Three…
After 2-3 Months…After 2-3 Months…
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

27. Continue regimen; check
HbA1c every 3 months
If fasting BG in target range, check BG before lunch, dinner, and bed.
Depending on BG results, add second injection
(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)
Recheck pre-meal BG levels and if out of range, may need to add another
injection; if HbA1c continues to be out of range, check 2-hr postprandial levels
and adjust preprandial rapid-acting insulin
If HbA1c ≤7%...
Bedtime long-acting insulin
(initiate with 10 units or 0.2 units per kg)
Check FG and increase dose until in target range.
If HbA1c ≥7A%...
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
Pre-bed BG out of range: add
rapid-acting insulin at dinner
Continue regimen; check
HbA1c every 3 months
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c ≤7%... If HbA1c ≥7%...
27
Step Two…
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

28. 28
Step Three:Step Three:
Further Intensifying InsulinFurther Intensifying Insulin
• Recheck pre-meal blood glucose and
if out of range, may need to add a third
injection:
• If HbA1c is still ≥ 7%
–Check 2-hr postprandial levels
–Adjust preprandial rapid-acting insulin
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

29. Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
Continue regimen; check
HbA1c every 3 months
If fasting BG in target range, check BG before lunch, dinner, and bed.
Depending on BG results, add second injection
(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)
Recheck pre-meal BG levels and if out of range, may need to add another
injection; if HbA1c continues to be out of range, check 2-hr postprandial levels
and adjust preprandial rapid-acting insulin
If HbA1c ≤7%...
Bedtime long-acting insulin
(initiate with 10 units or 0.2 units per kg)
Check FG and increase dose until in target range.
If HbA1c ≥7%...
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
Pre-bed BG out of range: add
rapid-acting insulin at dinner
Continue regimen; check
HbA1c every 3 months
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c ≤7%... If HbA1c ≥7%...
29
Step Three…

30. 30
Premixed InsulinPremixed Insulin
• Not recommended during dose
adjustment .
• Can be used before breakfast and/or
dinner if the proportion of rapid- and
intermediate-acting insulin is similar
to the fixed proportions available
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

31. Basal Insulins in Type 2 DM
• NPH at HS - duration of action short:
- usually need AM injection
- nighttime hypoglycemia is a
problem
31

32. Basal Insulins in Type 2 DM
• Analogs
- Degludec - true once daily injection
- Glargin - likely to succeed as true
once daily injection
- Detemir – Basal insulin
32

33. 33
Inhaled InsulinInhaled Insulin
• Approved in the U.S. in 2006 for the
treatment of type 2 diabetes and then had
been withdrawn from the market.
• In June, 2014 another inhaled insulin
(Afreeza) got US FDA approval and Aventis
bought the patent of it for commercial
production and marketing.
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

34. Upgrade and Intensification
Selecting alternative insulin or altering
the current treatment regimen (e.g.
Increasing number of daily doses)

35. Need of Changing Insulin Regimen
• Failure to attain or maintain target
glycemic status (FPG/PPG or HbA1C).
• H/O repeated hypoglycemia
• Lifestyle issues

36. Changing from Other regimens to
Basal/Bolus Insulin
~50%
Basal*
Total Daily DoseTotal Daily Dose
(~70-75% of prior insulin regimen TDD)(~70-75% of prior insulin regimen TDD)
~50%
Bolus*
Usually divided into 3 premealUsually divided into 3 premeal
dosesdoses*Range: 40 to 60%*Range: 40 to 60%

37. An Example:
• Mr. M: 58 yrs with history type 2 diabetes for
8 years
–In addition to OHAs, he is on 70/30 premixed
insulin: 30 u AM and 15 u PM
–Current Total Daily Dose = 45 u of 70/30
–However, he has been having difficulty with
wide glycemic excursions.

38. ………….An Example:
• After discussing his options in detail, he
is willing to begin with basal/bolus
regimen:
• New TDD= 45 u x .75 = 33.75 = 34 u
– Basal = 17 u Degludec at bedtime
– Bolus = 17 u total / 3 = 5.6 u = 5 u
aspart/Glulisine immediately before meals.

39. Another method
• Same patient: Mr. M on 70/30 insulin:
30 u AM and 15 u PM
– Current Total Daily Dose = 45 u of 70/30
• Instead, some clinicians prefer to
instead calculate the new basal/bolus
doses independently of each other
– Current Basal= 0.70 x 45 u TDD = 31.5 u N
– Current Bolus= 0.30 x 45 u TDD = 13.5 u.

40. ………….Another method
• Then, use 70 to 75% of prior NPH,
but divide prior short acting into 3
premeal doses
– New Basal= 0.75 x 31.5 u N = 24 u
Degludec, Glargine, Detemir.
– New Bolus= 13.5 u R / 3 = 4.5 u (round up
or down) Aspart or Glulisine

41. So which method is best?
• This is where the “Art of Medicine”
comes in:
– If patient has been having difficulty with
hypoglycemia, then start any new insulin
regimen with conservative doses.
– If patient, on the other hand, has been having
hyperglycemia, then one can be more
aggressive.
Remember: every patient is an individual!

42. A Quick Word on using Sliding
Scale Insulin….
Don’t!

43. Instead of Sliding Scale....
• Basal insulin is necessary even in the fasting
state
• Sliding scales do not provide physiologic insulin
needs
• Sliding scales often result in “chasing” of blood
sugars
• There can be wide glycemic excursions
Remember: Just because a diabetic’s FBG is <150 does not mean
that they need no insulin!
Think Supplementation or Correction Scale…

45. The Solution:
• In acutely ill hospitalized diabetics:
use continuous IV insulin

46. ………The Solution:
• If one must use an insulin scale in an outpatient or
stable inpatient setting:
• Insulin scale should only supplement a routine
scheduled regimen of basal and premeal insulin
• May use to correct for hyperglycemia between
scheduled doses of insulin
• It should NEVER be ordered such that the scale is
the only source of insulin for the patient

47. Drawbacks of intensive
insulin regimens
• Requires frequent monitoring of glucose
• Multiple daily injections of insulin
• Requires intensive patient education/on-
going support
• Newer insulin analogues require less
injections a but are more expensive
47

48. 48
Key Take-Home MessagesKey Take-Home Messages
• Insulin is the oldest, most studied, and most
effective antihyperglycemic agent, but can
cause weight gain (2-4 kg) and
hypoglycemia.
• Insulin analogues with longer, non-peaking
profiles may decrease the risk of
hypoglycemia compared with NPH insulin.

49. 49
Key Take-Home MessagesKey Take-Home Messages
• Premixed insulin is not recommended
during dose adjustment.

50. 50
Key Take-Home MessagesKey Take-Home Messages
• When initiating insulin, start with bedtime
or morning long-acting insulin.
• After 2-3 months, if FBG levels are in
target range but HbA1c ≥7%, check BG
before lunch, dinner, and bed,
and, depending on the results, add 2nd
injection.

51. 51
Key Take-Home MessagesKey Take-Home Messages
• After 2-3 months, if pre-meal BG out of
range, may need to add a 3rd
injection; if
HbA1c is still ≥7% check 2-hr postprandial
levels and adjust preprandial rapid-acting
insulin.
• Adjust one insulin at a time. Begin with the
insulin that will correct the first problem
blood glucose of the day.

52. 52
Key Take-Home MessagesKey Take-Home Messages
• It is difficult to obtain optimal control
without occasional, mild episodes of
hypoglycemia.

53. 53
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