1) Insulin therapy is recommended for type 2 diabetes patients with an HbA1c ≥9%, significant hyperglycemia, or when other treatments fail to control blood glucose levels. 2) There are several options for insulin therapy including basal insulin only, premixed insulin, or basal-bolus regimens. Basal insulin aims to provide background insulin levels while bolus insulin covers mealtime spikes. 3) When initiating insulin, it is important to assess the patient's needs, educate them on self-monitoring, and start at a low dose such as 0.1-0.2 units/kg of basal insulin daily to minimize risks of hypoglycemia and weight gain. The dose is then gradually

2. Diabetes in clinical
practice(2)
Dr. Hazem Samy Matar
Assistant lecturer of internal medicine,diabetes and
endocrinology

3. Approach To Starting and Adjusting
Insulin in Type 2 Diabetes
ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S46. Figure 7.2;
adapted with permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149

4. Normal Insulin Secretion
Mealtime (bolus)
insulin needs ~ 50%
Background (Basal) Insulin Needs ~ 50%
Kruszynska et al. Diabetologia 30: 16-21, 1987
Polonsky et a. J. Clin. Invest. 81: 442-48, 1988
Time

5. The Role of Insulin Therapy
Relative Insulin
Deficiency
Pre-diabetes and
Type 2 Diabetes
Insulin
Resistance
Incretin Dysfunction
Insulin
Deficiency
Type 1 Diabetes
Critical role in both Type 1 and Type 2 diabetes
• Greatest potency of available therapies
• Demonstrated benefit – multiple clinical trials

6. Insulin Therapy Nomenclature
• Basal insulin – long-acting insulin that is used to provide a background
level of insulin throughout the day and night
• Bolus insulin – short- or rapid-acting insulin that is used to provide an
increased level of insulin for a short period
• Prandial insulin – bolus insulin administered prior to a meal
• Correction insulin - bolus insulin administered to lower a high blood glucose
level
• Pre-mixed (or Biphasic) insulin- combination of short- or rapid-acting and
intermediate or long-acting insulin used to try to cover both fasting and
prandial insulin needs

7. Insulin Therapy Options
• Basal insulin only
• Bolus (Prandial) only
• Premixed
• Basal plus limited-meal bolus (‘Basal plus’)
• Basal-Bolus (i.e. multiple daily injections - MDI)
• Basal-Bolus (i.e. continuous subcutaneous insulin infusion [CSII],
“Insulin Pump”)

8. Action Profiles of Injectable Insulins in
T2DM Patients

9. HbA1c ≥ 9%
Insulin as
initial drug
therapy
Insulin is
strongly
considered
Insulin is
mandatory
Significantly
hyperglycemic
symptoms
PG > (300-350
mg/dl)
HbA1c ≥ (10-
12%)
When it is the time for
insulin!!
Catabolic
features are
exhibited
Ketonurea is
demonstrated
American Diabetes Association. Diabetes Care. 2012;35:1364-1379
Insulin as 3rd
drug agent to
two drug
combination
HbA1c ≥ 8.5%

10. INITIATION AND ADVANCEMENT OF
INSULIN THERAPY IN TYPE 2
DIABETES
Objectives:
1. Understand where insulin treatment fits in the current
guidelines of the ADA and EASD
2. Recognize that there are numerous insulin regimens with
various benefits and risks
3. Become familiar with the initiation and advancement of
basal, premixed, and basal/bolus insulin regimens

11. Insulin Therapy Indications
(1) When significant hyperglycemia (metabolic derangement) is
present at diagnosis (e.g., HbA1c ≥10%); or fasting plasma
glucose (FPG) is >13.9 mmol/L (>250 mg/dl) or random glucose is
>16.7 mmol/L (>300 mg/dl)
(2) When symptomatic (e.g., sudden persistent weight loss, ketosis)
(3) When multiple non-insulin therapies fail to achieve individualized
glycemic targets
(4) When rapid achievement of glucose control is desired (e.g., to
induce “clinical remission,” see Module 2)

12. Preparation for Insulin Initiation
Clinicians are required to:
1. Identify the glycemic defect (i.e., periods of hyperglycemia—fasting
hyperglycemia, postprandial hyperglycemia, and overall glycemic
derangement)
2. Address the concerns of the person with diabetes (see Module 6)
3. Select the appropriate insulin regimen and insulin-delivery device
4. Review/adjust non-insulin therapies
5. Assess the risk of hypoglycemia
6. Review diet and activities of daily living (see Module 6)

13. Principles to Follow for Individuals
Concomitantly
Treated with Non-insulin Agents
1) DPP-4 inhibitor, GLP-1 receptor agonist, α-glucosidase inhibitor,
and/or metformin are usually maintained at usual dose although
they need careful monitoring;
2) Insulin secretagogue dose is often reduced or stopped due to
risk of hypoglycemia and/or excessive weight gain;
3) TZD dose is often reduced or stopped due to risk of
hypoglycemia, excessive weight gain, edema, and/or heart
failure.

14. Clinical Efficacy –
Proportion of patients at HbA1c target <7% with eight
classes of
anti-diabetic drugs in type 2 diabetes: systematic review of
218 randomized controlled trials with 78,945 patients
Non-insulin Therapies Insulin Therapies
Esposito et al. Diabetes, Obesity and Metabolism 14: 228–
233, 2012.

15. Clinical Effectiveness-
Glycemic Response and Attainment of A1C Goals Following Newly
Initiated Insulin Therapy for Type 2 Diabetes
Nicholls et al. Diabetes Care 35:495–497,
2012

16. Guidelines

17. Antihyperglycemic Therapy in
Type 2 Diabetes
ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S43. Figure 7.1;
adapted with permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149

18. Sequential Insulin Strategies in T2DM
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of
print]
Management of Hyperglycemia in Type 2 Diabetes:
Sequential Insulin Strategies

19. Basal Insulin

20. Basal insulin in type 2 diabetes
(e.g. LA 0.1-0.2 U/kg or 10U)
Non-insulin therapies
LA = Long-Acting insulin: Glargine, Detemir
Basal Insulin in Type 2 Diabetes

21. Basal Insulin Options
Glargine and Detemir:
• Lasts up to 24 hours; BID dosing may be required (less
common in T2DM vs. T1DM)
• Decreases risk of hypoglycemia (especially nocturnal)
• Less weight gain
• Less variability in effect
Neutral Protamine Hagedorn (NPH):
• Lasts 10–16 hours
• Peaks 8–10 hours
• Less expensive
• May partly cover meal (e.g., breakfast if taken in morning)
but can result in later hypoglycemia (e.g., early afternoon)
Riddle et al. Diabetes Care. 26:3080-3086; 2003
Raskin et al Diabetes Care. 28:260-265; 2005

22. • Most insulin regimens take into account the individual’s weight at
initiation because doing so will help prevent adverse reactions caused by
over-insulinization (most notably hypoglycemia and weight gain).
• Basal insulin is typically begun at a low dose (e.g., 0.1–0.2 units/kg
per day).
• The most convenient strategy is with a single injection of basal insulin
administered before the evening meal or at bedtime, at an initial dose of
0.1units/kg. This will ensure that changes in blood glucose levels will be
gradual.
• Under special conditions, such as significant hyperglycemia (HbA1c
≥9%) and/or obesity, a starting dose of 0.2 units/kg may be used.
• An alternative, non-weight-based option is to start most individuals
empirically with 10 units, or in obesity up to 20 units, of basal insulin
(i.e., long-acting or intermediate-acting).
Initiating Basal
Insulin

23. Advancing Basal Insulin
If most AM fasting BG
>120 mg/dL
(>6.7 mmol/L)
Titrate until fasting glucose at target BG
• Increase 2 units [or 4 units if FBG >180
mg/dl or 10 mmol/L] every 3 days
• If dose reaches ~0.5 units/kg body weight,
consider adding mealtime insulin
If most AM fasting BG
<120 mg/dL
(<6.7 mmol/L) and
A1C remains above target
Test pre–evening meal and bedtime
(or 2-hour post–evening meal) and consider
need for mealtime insulin
If hypoglycemia or FPG
< 70 mg/dL
Reduce insulin dose by 3 units or 10%,
whichever is greater

24. Premixed Insulin

25. Insulin Analog Mix 75/25 or 70/30
Starting Premixed Insulin Analogue
Regimen

26.  Relatively easy to use
 Covers insulin requirements
through most of day
 Not very physiological
 Less flexibility than
basal(±bolus)
 Greater likelihood of
hypoglycemia
 More weight gain than basal
 Emerging evidence supports
better A1C reduction with
basal/bolus
Premixed Insulin Therapy
Supporting Evidence Non-supporting Evidence

27. • Most insulin regimens take into account the individual’s weight at
initiation because doing so will help prevent adverse reactions caused by
over-insulinization (most notably hypoglycemia and weight gain).
• When using premixed insulin, insulin secretagogues are often
discontinued and other non-insulin therapies should be reconsidered.
• The effectiveness of these medications should be reconsidered in light
of the action of the premixed insulin.
• If the HbA1c is ≥9%, the starting dose of premixed insulin is 0.2
units/kg before the morning and evening meals (total daily dose 0.4
units/kg).
• If the HbA1c is <9%, the starting dose is 0.1 units/kg before the
morning and evening meals (total daily dose 0.2 units/kg).
• Based on glucose monitoring, premixed insulin adjustments of 2 units
is typically recommended.
Initiating Premixed
Insulin

28. Part 4: Advancing Insulin Therapy

29. Rapid-acting insulin at meals Long-acting
insulin at bed
Starting a Basal and Mealtime
(e.g., Basal-bolus) Insulin Regimen

30. Advancing Insulin Therapy from Basal Insulin
 Halt or decrease all insulin
secretagogues
 TZDs are often reduced or
stopped due to risk of
hypoglycemia, excessive
weight gain, edema, and/or
heart failure
 Initiate SMBG before each
meal (injection)
 Consider reducing total basal
dose by 0.1 units/kg
 Identify highest consistent
post meal glucose or biggest
meal
 Start with 0.1 units/kg or 4
units short- or rapid-acting
insulin
 The dose can be further
modified by adding 2 units of
short- or rapid-acting insulin
every 3 days until postprandial
glucose is ≤180 mg/dl (10
mmol/l) as per local titration
guidelines.
 Titrate to 0.2 units/kg, and if
the target has not been
reached consider dietary
modifications and/or the
addition of a second bolus
injection and subsequent
injection to full basal-bolus
insulin regimen if needed

31. Adapted from Howey DC, et al. Diabetes. 1994;43(3):396-402
Hours
10
8
6
4
2
0
0 1 2 3 4 5 6 7 8 9 10 11 12
InsulinActivity
RHI
Timing of
food
absorbed
Analog Insulin
Rapid-acting Insulin Analogues Versus
Short-acting Insulin
RHI = regular human insulin.

32. • A basal/bolus insulin regimen can be considered at diagnosis when
rapid achievement of glucose control is desired (e.g., symptomatic, or to
induce “clinical remission,” see Module 2).
• Basal/bolus regimens can also be considered when the combination of
basal or premixed insulin and non-insulin therapies are no longer
effective.
• The minimal starting total daily dose is 0.2 units/kg divided as 50%
long- or intermediate-acting and 50% short- or rapid-acting insulin.
• The basal and bolus doses can be titrated separately. Adequate glucose
monitoring should be consistent with clinical needs and safety.
• It is recommended that this intensive insulin regimen should be
initiated and supervised by a specialist with expertise in diabetes.
• An additional option for intensive insulin therapy is premixed insulin 2–
3 times daily (see previous section on starting and adjusting premixed
insulin).
Initiating Basal-Bolus Insulin
Regimen

33. Starting Basal + Bolus (mealtime) Insulin:
A1C <9% A1C ≥9%
Basal-Bolus
insulin
0.2 units/kg/ day
Basal 0.1 units/kg
+
Mealtime 0.1
units/kg
0.4 units/kg/day
Basal 0.2 units/kg
+
Mealtime 0.2
units/kg
• Stop or reduce insulin secretagogue
• TZDs are often reduced or stopped due to risk of hypoglycemia,
excessive weight gain, edema, and/or heart failure
• Select and calculate starting dose
• Divide 50% background, 50% mealtime
Mazze R, et al. Staged Diabetes Management Adult Quick Guide, 5th Edition Revised, 2010
International Diabetes Center

34. Calculating Basal + Mealtime Insulin Dose:
Calculate insulin dose
Weight in kg ______ x units/kg _____ = _____units long-acting
(LA)
(RA) 80 x units/kg _____ = _____units rapid-acting
Example: T2DM Patient (80 kg) with A1C of 9.6% on
metformin and insulin secretagogue
80 0.2 16
Plan Insulin AM Noon PM Bed
LA 16
RA 5 5 6
0.2 16
Total starting dose = 0.2 units/kg

35. Advanced Skills:
CHO Counting and Correction Factor
 Determine Insulin: CHO ratio (I:C)
• Amount of insulin covered by 1 units bolus insulin
• Calculated using “450 rule”; start with Total Daily Dose (TDD)
450/TDD = amount of CHO covered by 1 units insulin
 Determine Insulin Sensitivity (“Correction”) Factor
• Number of points 1 units insulin will drop BG
• Calculated using “1500 rule” for short-acting insulin
(and “1800 rule” for rapid-acting insulin analog)
• 1500/TDD = expected BG drop covered by 1 units insulin
Mazze R, et al. Staged Diabetes Management Adult Quick Guide, 5th Edition Revised, 2010
International Diabetes Center

36. Principles for Insulin Therapy
• Narrow the gap between guideline and clinical practice
• A timely introduction of insulin therapy in type 2 diabetes could
protect β-cell function and facilitate effective glycemic control.
• Insulin is highly effective but can pose a challenge for both patients
and healthcare practitioners.
• Clinical and psychological insulin resistance are major obstacles to
better glycemic control.
• Basal-insulin-based optimal insulin regimens provide a safer way to
achieve glucose control with fewer episodes of hypoglycemia and less
weight gain.
• Effective patient-centered insulin therapy can be achieved
safely by recognizing and overcoming the various inherent
challenges.

37. An educational program of the International Diabetes Center.
OBJECTIVES
1. Understand where insulin treatment
fits in the current guidelines of the
ADA and EASD.
1. Recognize that there are
numerous insulin regimens with
various benefits and risks.
2. Become familiar with the
initiation and advancement of
basal, premixed, and basal/bolus
insulin regimens.
SUMMARY
1. Insulin may be initiated after failure of
mono or combination non-insulin
therapies, when symptomatic,
glucotoxicity, or at the request of the
individual with diabetes .
2. Basal, basal/bolus, NPH, premixed
insulin regimen can be used safely and
effectively with appropriate education
and glucose monitoring.
3. Basal, premixed, and basal/bolus
insulin can safely be initiated at low
dose and titrated based on SMBG .
Initiation and Advancement of Insulin
Therapy in Type 2 Diabetes