Ueda2016 symposium - metformin ® xr - mohamed mashaheet

Metformin ® XRBenefits of continuing

Metformin XR with the use

of Insulin

Mohamed Mashahit Fayoum Universit

Agenda

Introduction

Diabetes burden 2016 updates

Metformin ® XR, What do the guidelines say?

Metformin e® XR rationale & Clinical benefits

Metformin ® XR Reshaping Metformin efficacy

Type 2 DM is an old disease….

….still need to be revised

First Description of Diabetes 1550 BC

This papyrus found in 1862 contains descriptions of various diseases including a polyuric state resembling diabetes mellitus.

Treatment recorded was a 4 day course of a liquid extract of bones, wheat, grain, grit, green lead and earth.

Agenda


Glucophage® XR, What do the guidelines say?

Glucophage® XR rationale & Clinical benefits

Glucophage® XR Reshaping Metformin efficacy

Diabetes: A global emergency

IDF Diabetes Atlas, 7th edition

Estimated number of people with diabetes worldwide and per region in 2015

and 2040 (20-79 years)

Diabetes around the world



One in 7 adults have diabetes in Egypt

Diabetes (20-79 years)2015 2040

Number of people with diabetes

(diagnosed and undiagnosed)

7.8 million

(3.8-9.0 million)

15.1 million

(7.3-17.3 million)

Raw country prevalence14.8%

(7.2-17.1%)

17.8%

(8.6-20.4%)

Mean diabetes-related expenditure per person

with diabetesUSD 219 USD 218

Number of adults with undiagnosed diabetes3.2 million

(1.5-3.7 million )

6.2 million

(3-7.1 million)

Percent of undiagnosed diabetes 41.20%

Number of deaths due to diabetes78,200

(42,000-87,800)

Percent of deaths before age 60 43.60%

Top 10 countries


Top ten countries/territories for number of people with diabetes (20-79 years), 2015 and 2040

An estimated

average of

1,622 USD per

person with

diabetes was

spent on

diabetes-related

health

expenditures in

2015

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 patients

Life 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

Agenda


Metformin ® XR, What do the guidelines say?



Glucophage XR in guidelines:

Add basal or

intensify insulin

Lifestyle intervention and metformin

Add sulfonylurea

(least expensive)

Add basal insulin

(most effective)

Add TZD

Add TZDAdd basal

insulin***

Add

sulfonylurea

If HbA1c ≥7%*

If HbA1c ≥7%

If HbA1c ≥7%

Intensive insulin + metformin +/− TZD**

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Nathan DM et al. Diabetologia 2008;51(1):8-11.

Intensify

insulin***

ADA/EASD Management Algorithm

ADA/EASD Consensus Algorithm for

Management of DiabetesDiabetes Care. 2009, 32:193-203

At diagnosis:

Lifestyle

+

Metformin

Lifestyle+Metformin

+

Pioglitazone(No hypoglycemia, edema, CHF, bone loss)

Lifestyle+Metformin

+

Sulfonylurea

Lifestyle+Metformin

+

Intensive insulin

Lifestyle+Metformin

+

Basal Insulin

Lifestyle+Metformin

+

GLP1 (No hypoglycemia, wt loss, Nausea/vomiting)

Lifestyle+Metformin

+

Pioglitazone

+

Sulfonylurea

Lifestyle+Metformin

+

Basal Insulin

Tier 2: less well-validated

therapies

Tier 1: Well-validated core therapies

Step 1 Step 2 Step 3

Amylin agonists, Glinides

DPP-4 inhibitors may be

appropriate in selected

patients

*Useful when

hypoglycemia is to be

avoided

IDF guidelines as of December 2011

IDF Treatment algorithm 2011

www.idf.org/treatment-algorithm-people-type-2-diabetes

IDF treatment algorithm for people with type 2 diabetes developed 2011

http://www.idf.org/

HbA1c > 7%

HbA1c > 7%

ADA-EASD Position Statement (2012)

Antihyperglycaemic therapy for T2DM

Inzucchi SE et al . Diabetes Care 2012; April 19th online e-pub DOI:10.2337/dc12-0413

Metformin

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

Glucophage® XR is the optimal 1st line therapy in all Guidelines

Glucophage XR in guidelines:

Heart Attack Stroke

39%

Reduction

41%

Reduction

UKPDS 34. Lancet 1998; 352: 854-65

* versus lifestyle therapy

Improved Clinical Outcomes with

metformin - fewer life threatening

complications*

The legacy effect of Metformin on Macrovascular complications from UKPDS 10 years Trial follow up.

Cardiovascular benefits of Metformin:

Treatment algorithms of T2DM

ADA/EASD 2015 update:

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...“

“Insulin plus metformin is a particularly effective means of

lowering glycaemia while limiting weight gain...“



Metabolic

Benefits

Cardiovascular

Benefits

Glycaemic

Benefits

Insulin requirements

Agenda



Metformin® XR rationale & Clinical benefits


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

“...Metformin, reduce the risk of Macrovascular

disease after a follow-up period of 4.3 years by

39%”

Benefits of continuing Metformin with Insulin in T2DM: (Glycemic benefits)

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

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

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

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

Kooy A. Arch Intern Med 2009; 169: 616-25

Metformin plus insulin

Placebo plus insulin

Metformin plus Insulin – health

outcome benefits in type 2 diabetes

over 4.3 years

39%

GI disturbance

ConvenienceDose

2 gm/day

Metformin XR rationale:

Metformin XR rationale:

Metformin XR rationale: (GI side effects)

Glucophage 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/dayand

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%

Glycemic benefits of 2gm/day:

G 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

Agenda




Metformin ® XR Reshaping Metformin efficacy

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

Contra-indicationsBenefits

Holstein A Diabetologia 2005; 48: 2454-9

Metformin: Contra-indications

• Severe renal dysfunction.

• Severe liver disease.

• Use of IV contrast media.

• Major surgical procedures.

• Congestive heart failure.

• History of alcohol abuse.

Metformin: Contra-indications

eGFR level

(ml/min per 1.73 m2)Action

> 60No renal contraindication to metformin

Monitor renal function annually

< 60 and > 45

Continue use

Increase monitoring of renal function

(every 3-6 months)

< 45 and > 30

Prescribe metformin with caution

Use lower dose (e.g., 50%, or half-maximal dose)

Closely monitor renal function (every 3 months)

< 30 Stop metformin

Lipska KJ et al. Diabetes Care 2011;34:1431-1437

Metformin: Renal Function

Take home message:

Insulin partner- More glyceamic control

- Decreases insulin requirements

- Benefits on lipid profile

- Benefits in weight reduction

2% reduction in HbA1c

Least GI upset

Once daily dosing

Ueda2016 symposium - metformin ® xr - mohamed mashaheet

Health & Medicine

Transcript of Ueda2016 symposium - metformin ® xr - mohamed mashaheet