This document discusses challenges and solutions for insulin therapy in primary care. It begins by reviewing different glucose-lowering medications and their typical A1C reduction, with insulin providing the greatest reduction of at least 2.5%. The document then recommends starting insulin first for patients with A1C over 10%, fasting blood sugar over 250 mg/dl, or random blood sugar consistently over 300 mg/dl. It advocates that replacement insulin therapy should mimic the body's natural insulin profile. The rest of the document discusses the benefits of basal insulin, particularly insulin glargine, in reducing risks of hypoglycemia and improving 24-hour glucose control compared to NPH insulin. It emphasizes that education for patients on insulin therapy is important.

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
Insulin(mU/l)
06.00 12.00 24.0018.00
0
15
30
45
06.00
Breakfast Lunch Dinner
Endogenous insulin secretion
Ideal basal insulin
Ideal prandial insulin
Adapted from Kruszynska YT, et al. Diabetologia 1987;30:16–21.
Time (hours)

17. Why Basal insulin Early?

18. 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)
400
300
200
100
0
06.00 06.0010.00 14.00 18.00 22.00 02.00
Plasmaglucose(mg/dl)
Normal
Meal Meal Meal
20
15
10
5
0
Plasmaglucose(mmol/l)
Why Basal insulin Early?
Hyperglycaemia due to an increase in fasting glucose
T2DM
Treating fasting hyperglycemia lowers
the entire 24-hour plasma glucose profile

26. Reduced risk of nocturnal
hypoglycaemia with insulin glargine
NPH
Insulin glargine
p<0.001
p<0.002
Eventsperpatient–year
All nocturnal
hypoglycaemia
Confirmed nocturnal
hypoglycaemia
p<0.001
* **
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.
44%
risk reduction
42%
risk reduction
48%
risk reduction
6.9
5.5
2.5
4.0
3.1
1.3
0
1
2
3
4
5
6
7
8

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

28. 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
patients treated with NPH plus OADs
i
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. 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
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
The study duration was 9 months, followed by optional 20- and 32-month extension
phases

i

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

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