METFORMIN XR, A RATIONAL

DESTINATION IN TYPE2

MANAGEMENT

Mesbah Sayed Kamel

MD

DIABETES BURDEN IN 2014

DIABETES BURDEN IN 2014

DIABETES BURDEN IN 2014

DIABETES BURDEN IN 2014

DIABETES BURDEN IN 2014

DIABETES BURDEN IN 2014_EGYPT

DIABETES BURDEN IN 2014_EGYPT

People with

DIABETES

/6

DIABETES BURDEN IN 2014_EGYPT

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

Galega officinalis plant treating

diabetes since ancient time

French lilac, professor-

weed

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

1977 Phenformin

withdrawn in

USA

Pronounced

dead

1977

Phoenix rising from

the ashes

2006 Joint

ADA/EASD

consensus

algorithm

FDA in

1995

UKPDS

1998

METFORMIN IN GUIDELINES:

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:

ADA/EASD 2015 UPDATE:

THE LEGACY EFFECT OF METFORMIN ON MACROVASCULAR

COMPLICATIONS FROM UKPDS 10 YEARS TRIAL FOLLOW UP.

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

1- effective

2- Safe

3- Cardiac protection

4-Reasonable Cost

The perfect anti-diabetic

drug

• 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?

Metformin

Mechanism of

action

Not fully

understood

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

Mechanism of action

Inhibition of cell growth

Memmott R M et al. Cancer Prev

Res 2010;3:1066-1076

METFORMIN

1. Favorable lipid effects

2. Weight loss

3. Increased fibrinolytic activity

4. Decreased platelet aggregability

5. Favorable effect on hypertension

Additional actions

Metformin and

Cancer

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

Glucophage® XR in the Guidelines

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:

Benefits of continuing Metformin with Insulin in T2DM: (HbA1c reduction)

Benefits of continuing Metformin with Insulin in T2DM: (Lipid profile)

Metformin

Benefits of continuing Metformin with Insulin in T2DM: (Weight reduction)

Benefits of continuing Metformin with Insulin in T2DM: (Insulin requirements)

GI disturbance

Convenience

Dose

2 gm/day

METFORMIN XR RATIONALE:

METFORMIN XR RATIONALE:

METFORMIN XR RATIONALE: (GI SIDE EFFECTS)

METFORMIN XR RATIONALE: (OPTIMAL DOSE)

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: (COMPLIANCE)

METFORMIN XR RATIONALE: (FORMULATION)

The Gel-Shield

Diffusion System

Provides

More Prolonged

Metformin

Release

Absorption of

Metformin is

Slower and longer

PATIENTS STARTED ON METFORMIN XR AT

DIAGNOSIS – TOLERANCE OVER 12

MONTHS

SWITCHOVER TO METFORMIN XR

IMPROVES ADHERENCE IN ROUTINE

GENERAL PRACTICE

METFORMIN XR DOSING SCHEDULE:

Divided Dose Once Daily

The Sultan…

of anti-

diabetic

medications

Metformin

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

Thank

you