This document discusses the benefits of continuing metformin XR when insulin is added for treatment of type 2 diabetes. It notes that metformin is recommended as first-line therapy in treatment guidelines and can provide cardiovascular benefits when used long-term. When used in combination with insulin, metformin can help control blood glucose levels better while limiting weight gain and insulin requirements compared to insulin alone. The document recommends metformin XR over other formulations due to its once daily dosing and reduced gastrointestinal side effects.

1. Metformin ® XR
Benefits of continuing
Metformin XR with the use
of Insulin

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Mohamed Mashahit
Fayoum Universit

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Agenda
Introduction
Diabetes burden 2016 updates
Metformin ® XR, What do the guidelines say?
Metformin e® XR rationale & Clinical benefits
Metformin ® XR Reshaping Metformin efficacy

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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.

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Agenda
Diabetes burden 2016 updates
Glucophage® XR, What do the guidelines say?
Glucophage® XR rationale & Clinical benefits
Glucophage® XR Reshaping Metformin efficacy

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Diabetes: A global emergency
IDF Diabetes Atlas, 7th editio
Estimated number of people with diabetes worldwide and per region in 2015
and 2040 (20-79 years)

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Diabetes around the world
IDF Diabetes Atlas, 7th editio

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IDF Diabetes Atlas, 7th editio
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 prevalence
14.8%
(7.2-17.1%)
17.8%
(8.6-20.4%)
Mean diabetes-related expenditure per person
with diabetes
USD 219 USD 218
Number of adults with undiagnosed diabetes
3.2 million
(1.5-3.7 million )
6.2 million
(3-7.1 million)
Percent of undiagnosed diabetes 41.20%
Number of deaths due to diabetes
78,200
(42,000-87,800)
Percent of deaths before age 60 43.60%

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Top 10 countries
IDF Diabetes Atlas, 7th editio
Top ten countries/territories for number of people with diabetes (20-79 years), 2015 and 2040

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An estimated
average of
1,622 USD per
person with
diabetes was
spent on
diabetes-related
health
expenditures in
2015

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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 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

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Agenda
Diabetes burden 2014 updates
Metformin ® XR, What do the guidelines say?
Glucophage® XR rationale & Clinical benefits
Glucophage® XR Reshaping Metformin efficacy

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Glucophage XR in guidelines:

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Add basal or
intensify insulin
Lifestyle intervention and metformin
Add sulfonylurea
(least expensive)
Add basal insulin
(most effective)
Add TZD
Add TZD
Add 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

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ADA/EASD Consensus Algorithm for
Management of Diabetes
Diabetes 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

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IDF guidelines as of December 2011

22. Page  22 IDF Treatment algorithm 2011
www.idf.org/treatment-algorithm-people-type-2-diabetes
IDF treatment algorithm for people
with type 2 diabetes developed 2011

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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

24. Page  24 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:

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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*

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

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Cardiovascular benefits of Metformin:

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Cardiovascular benefits of Metformin:

29. Treatment algorithms of T2DM

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ADA/EASD 2015 update:

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ADA/EASD 2015 update:

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Glucophage® XR in the Guidelines

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Glucophage® XR in the Guidelines

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Benefits of continuing Metformin with Insulin in
T2DM:
“Metformin is often continued when basal insulin is added,
with studies demonstrating less weight gain...“

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“Insulin plus metformin is a particularly effective means of
lowering glycaemia while limiting weight gain...“
Benefits of continuing Metformin with Insulin in
T2DM:

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Benefits of continuing Metformin with Insulin in
T2DM:
Metabolic
Benefits
Cardiovascular
Benefits
Glycaemic
Benefits
Insulin
requirements

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Agenda
Diabetes burden 2014 updates
Glucophage® XR, What do the guidelines say?
Metformin® XR rationale & Clinical benefits
Glucophage® XR Reshaping Metformin efficacy

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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%”

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

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

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

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

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

44. Page  44 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%

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GI disturbance
Convenience
Dose
2 gm/day
Metformin XR rationale:

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Metformin XR rationale:

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Metformin XR rationale: (GI side effects)

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Glucophage XR rationale: (optimal dose)

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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%

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Glycemic benefits of 2gm/day:

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G Metformin XR rationale: (Compliance)

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Metformin XR rationale: (formulation)
The Gel-Shield
Diffusion System
Provides
More Prolonged
Metformin
Release
Absorption of
Metformin is
Slower and longer

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Agenda
Diabetes burden 2014 updates
Glucophage® XR, What do the guidelines say?
Glucophage® XR rationale & Clinical benefits
Metformin ® XR Reshaping Metformin efficacy

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Patients Started on Metformin ® XR at Diagnosis –
Tolerance Over 12 Months

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Switchover to Metformin ® XR Improves Adherence
in Routine General Practice

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Metformin XR dosing schedule:
Divided Dose Once Daily

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Contra-indicationsBenefits
Holstein A Diabetologia 2005; 48: 2454-9
Metformin: Contra-indications

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• Severe renal dysfunction.
• Severe liver disease.
• Use of IV contrast media.
• Major surgical procedures.
• Congestive heart failure.
• History of alcohol abuse.
Metformin: Contra-indications

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eGFR level
(ml/min per 1.73 m2)
Action
> 60
No 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

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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

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