1. Insulin Therapy
Primary Care Challenges
and Solutions
Prof.
Ibrahim El Ebrashy
Head Of The Diabetes & Endocrinology Center
Cairo University

3. A1C reduction with
glucose – lowering medications
Oral agents A1C (%)*
Sulfonylureas 1.5
Biguanides (metformin) 1.5
Glinides 1.0–1.5
Thiazolidinediones 0.8–1.0
DPP-IV inhibitors 0.5–0.9
α-Glucosidase inhibitors 0.5–0.8
Parenteral agents
Insulin ≥2.5
GLP analogues 0.6
Amylin analogues 0.6
*Monotherapy
DPP = dipeptidyl peptidase; GLP = glucagon-like peptide
Nathan DM. N Engl J Med. 2007;356:437-40.

11. When to Start Insulin First
ADA-EASD Consensus
• Severely catabolic patient
• Hemoglobin A1C > 10%
• FBS > 250 mg/dl (13.9 mmol/l)
• Random consistently > 300 mg/dl
(16.7 mmol/l)
Nathan et al. Diabetes Care 2006;29: 1963-1972

14. Replacement insulin therapy should mimic
endogenous insulin profile in
insulin-treated T2DM
Endogenous insulin secretion
Breakfast Lunch Dinner Ideal basal insulin
Insulin (mU/l)
45 Ideal prandial insulin
30
15
0
06.00 12.00 18.00 24.00 06.00
Time (hours)
Adapted from Kruszynska YT, et al. Diabetologia 1987;30:16–21.

17. Why Basal insulin Early?

18. Why Basal insulin Early?
Treating fasting hyperglycemia lowers
the entire 24-hour plasma glucose profile
400
Plasma glucose (mmol/l)
20
T2DM
Plasma glucose (mg/dl)
300
15
200 Hyperglycaemia due to an increase in fasting glucose
10
100
5
Normal
Meal Meal Meal
0 0
06.00 10.00 14.00 18.00 22.00 02.00 06.00
Comparison of 24-hour glucose levels in control subjects vs patients with diabetes (p<0.001).
Adapted from Hirsch I, et al. Clin Diabetes 2005;23:78–86. Time of day (hours)

26. Reduced risk of nocturnal
hypoglycaemia with insulin glargine
42%
NPH
8 risk reduction
6.9 44% Insulin glargine
Events per patient–year
7
risk reduction
6 5.5
p<0.001
5
p<0.001
4.0 48%
4
3.1 risk reduction
3 2.5
p<0.002
2
1.3
1
0
* **
All nocturnal Confirmed nocturnal
hypoglycaemia hypoglycaemia
Confirmed hypoglycaemia: *4 mmol/l (72 mg/dl); **3.1 mmol/l (56 mg/dl)
Riddle M. et al. Diabetes Care 2003;26:3080–6.

27. Insulin glargine reduces hypoglycemic
risk versus NPH in T2DM: Meta analysis
Risk of severe hypoglycaemia and severe nocturnal hypoglycemia reduced
by 46% (p = 0.04) and 59% (p = 0.02), respectively, with insulin glargine
Risk reduction mainly
observed at night
Symptomatic hypoglycaemic events
Mean (CI)
Overall 0.711 (0.586, 0.862); p = 0.001
Nocturnal 0.591 (0.486, 0.718); p < 0.001
Daytime 0.931 (0.771, 1.123); p = 0.455
0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0
Reduced risk Increased risk
Odds ratio
Rosenstock J, et al. Diabetes Care 2005;28:950−5.

28. LANTUS-BOT: after 5 years on Insulin Glargine,
83% of patients still did not require intensification

Retrospective cohort analysis from a German database comparing
the persistence of T2DM patients on basal insulin plus OADs with i
patients treated with NPH plus OADs
28
Pfohl M, et al. Adding insulin glargine to oral therapy in type 2 diabetes patients results in longer persistence with the treatment
regimen compared to NPH insulin. Poster presented at ISPOR 2008

29. Schreiber et al: following titration, Insulin Glargine + oral
antidiabetic drugs can provide sustained glycaemic
control

Observational study initiated in 12,216 insulin-naïve subjects with T2DM,
who added Insulin Glargine to their existing OAD treatment i
The study duration was 9 months, followed by optional 20- and 32-month extension
phases
29
Schreiber SA et al. Diabetes Obes Metab 2007;9(1):31–38; Schreiber SA, et al. Diabetes Technol Ther 2008;10(2):121–127

30. NEW THIN: switching from NPH to Insulin Glargine
improves HbA1c control in real life

Retrospective analysis from a UK database analysing the switch
from NPH to Insulin Glargine in patients with TD2M i
30
Gordon J, et al. ADA 2009, abstract accepted

41. At The End
Education For Our
Patients Is A Must

42. Advice For Physicians
 Don't wait forever. "Patient needs insulin
therapy,"
 Don't be afraid of hypoglycaemia, but be
aware of it.
 Consider combination therapy ( insulin +
OAD ).
 Don't under-insulinize.

47. Thank You