ueda2015 metformin xr, a rational destination in type2 dr.mesbah kamel.pptx
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UKPDS 33. Lancet 1998; 352: 837-53
Risk of disabling complications in T2DM patients
Complications
Heart attacks 27 patients
Stroke 10 patients
Retinopathy 23 patients
Premature Mortality
Diabetes deaths 28 patientsLife expectancy 5-7 years
100 Patients - Age 55
15 Years Follow-up
Patients with type 2 diabetes are at heightened risk of disabling complications versus non-diabetics
Metformin: Historical perspective
Remarkable story of metformin
The rise and fall and
the rise again of
metformin
Metformin became
available in the UK
1958. Jean sterne from paris the first to use metformin for
diabetes, he coined the name "Glucophage"
(glucose eater) for the drug and published his
results in 1957
The French
connection
Davidson JA Chan JCN. Scientific Handbook, Metformin :the Gold Standard John Wiley & Sons
SEMDSA guidelines. JEMDSA 2012;17:S1-S94
Country or
Region
UK (NICE)
Australia
Asia-Pacific
Fra (AFSSAPS)
Lat Am (ALAD)
USA (ADA)
Europe (EASD)
IDF (global)
South Africa
(SEMDSA)
Year
2005/8/9
2004
2005
2009
2007
2006/8/9/12
2006/8/9/12
2005/12
2012
BMI definition
of overweight
(kg/m2)
>25
None
>23
>28
>27
>25
>25
>25
>25
Overweight
Metformin
Metformin
Metformin
Metformin
Metformin
Metformin
Metformin
Metformin
Metformin
Non-overweight
Metformin
Metformin
Metformin, SU,TZD,AGI
Metformin, SU or AGI
Metformin
Metformin
Metformin
Metformin , SU
Metformin
Recommendations for initiating pharmacologic
therapy after failure of diet and exercise
Metformin in is the optimal 1st line therapy in all Guidelines
METFORMIN IN GUIDELINES:
THE LEGACY EFFECT OF METFORMIN ON MACROVASCULAR
COMPLICATIONS FROM UKPDS 10 YEARS TRIAL FOLLOW UP.
“Metformin is the first (and, to date, only) oral
antidiabetic agent to have a statement relating
to protection from diabetic complications
included in its European labelling”
1- Treatment of diabetes
2- Prevention of diabetes
3- In the treatment of PCO
4- In the treatment of GDM
Metformin, a drug for all seasons
5-In the treatment of ca
• Reduces insulin resistance
• Weight neutral
• Effective in lowering blood
glucose
• Lowers cardiovascular risk
• Reduces the risk of cancer
What would we desire in a
therapy for diabetes?
Weight loss
increased insulin
sensitivity
Improved
glycemia
Improved lipid
profile
Improved vascular
function
Sep 2010
British Journal of Cardiology
Drugs for Diabetes: Part 1 Metformin
Liver:
-Reduced fatty acid and
cholesterol synthesis
-Increased lipid oxidation
-Reduced gluconeogenesis
Skeletal muscles:
-Increased lipolysis and
lipogenisis
Adipose:
-Reduced lipolysis and
lipogenisis
Vascular endothelium:
-Increased NO bio-availability
Heart:
-Increased fatty acid uptake
and oxidation
-Increased glucose uptake
and glycolysis
. Activation of AMPK
METFORMIN
1. Favorable lipid effects
2. Weight loss
3. Increased fibrinolytic activity
4. Decreased platelet aggregability
5. Favorable effect on hypertension
Additional actions
Metformin may be the
shining star rising out of
the recent rediscovery
of the connection
between type 2
diabetes and cancer,
Pollak M "Metformin -- anti-cancer
potential" EASD 2010.
This old drug could well
perform a new trick for cancer
prevention -- and even
treatment
EASD: Metformin Still Hot Topic
in Cancer Prevention
“The secret of my influence has always been that it remained secret”
Salvador Dali
metformin Mechanism of action
Benefits of continuing Metformin with Insulin in T2DM:
“Metformin is often continued when basal
insulin is added,
with studies demonstrating less weight gain...“
Diabetologia
DOI 10.1007/s00125-012-2534-0
Unless there are prevalent contraindications,
metformin is the optimal first-line drug
Comprehensive cardiovascular risk reduction
must be a major focus of therapy
Benefits of continuing Metformin with Insulin in T2DM:
METFORMIN XR RATIONALE: (OPTIMAL DOSE)
The optimal dose of
metformin for the control
of glycaemia is in the
region of 2000 mg/day
and the average daily
dosage of metformin
achieved in routine
clinical practice lies
between 1000 mg and
2000 mg
in most European
countries.
2000 mg is the optimum dose of Metformin
reducing A1c by 2%
METFORMIN XR RATIONALE: (FORMULATION)
The Gel-Shield
Diffusion System
Provides
More Prolonged
Metformin
Release
Absorption of
Metformin is
Slower and longer
TAKE HOME MESSAGE:
METFORMIN XR
Reshape of Metformin
Increased adherence to treatment .
Least GI upset
Once daily dosing
Insulin partner- More glyceamic control
- Decreases insulin requirements
- Benefits on lipid profile
- Benefits in weight reduction
Effective: 2% reduction in HbA1c