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Insulin Therapy
Primary Care Challenges and Solutions
Prof.
Ibrahim El Ebrashy Head Of The Diabetes & Endocrinology Center
Cairo University
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.
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
Replacement insulin therapy should mimic
endogenous insulin profile in
insulin-treated T2DM
Ins
ulin
(m
U/l
)
06.00 12.00 24.00 18.00 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)
Why Basal insulin Early?
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 06.00 10.00 14.00 18.00 22.00 02.00
Pla
sm
a g
luc
ose (
mg
/dl)
Normal
Meal Meal Meal
20
15
10
5
0
Pla
sm
a g
luco
se (m
mo
l/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
Reduced risk of nocturnal hypoglycaemia with insulin glargine
NPH
Insulin glargine
p<0.001
p<0.002
Events
per
pati
ent–
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
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 risk Reduced risk
Risk reduction mainly observed at night
Rosenstock J, et al. Diabetes Care 2005;28:950−5.
Mean (CI)
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
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
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
At The End
Education For Our Patients Is A Must
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.
Thank You
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