Recent recommendationsRecent recommendationsfor the treatment of type 2 diabetesfor the treatment of type 2 diabetes

IDFIDF vs EASD ADA vs vs EASD ADA vs FrenchFrench A consensus?A consensus?

S. HALIMIS. HALIMI

•President of the French Guidelines HASPresident of the French Guidelines HAS•Vice President ALFEDIAMVice President ALFEDIAM•Vice President MGSDVice President MGSD

Percentage of diabetes among major CV and renal diseases

•European DialysisEuropean Dialysis

• and Transplantation Associationand Transplantation Association

6060

2020

4040

3030

5050

1010

Dia

bet

ic

Dia

bet

ic P

atie

nts

Pat

ien

ts (%

)(%

)

00

AmputationsAmputations

50%

Diabetes prevalence 3–5%Diabetes prevalence 3–5%

Myocardial InfarctionMyocardial InfarctionFemaleFemale MaleMale

25%25%33%33%

38%38%36%36%

GERGER FRFRUSUS GERGER FRFR

25%25%25%25%

USUS AustriaAustria

29%29%

StrokeStroke

30%30%27%27%

EUREUR

EDTA*EDTA* JapanJapan

ESRDESRD

http://www.idf.org

Diabetes is expected to cause 3.8 million deaths worldwide in 2007, about 6% of total global mortality, about the same as HIV/AIDS. Using World Health Organization (WHO) figures on years of life lost per person dying of diabetes, this translates into more than 25 million years of life lost each year.

Diabetes is expected to cause 3.8 million deaths worldwide in 2007, about 6% of total global mortality, about the same as HIV/AIDS. Using World Health Organization (WHO) figures on years of life lost per person dying of diabetes, this translates into more than 25 million years of life lost each year.

BP recommendations

• ADA EASDADA EASD– Goal: < 130/80 mmHgGoal: < 130/80 mmHg– Goal: < 125/75 mmHg if proteinuriaGoal: < 125/75 mmHg if proteinuria– Goal > to the drug utilizedGoal > to the drug utilized

• IDF IDF – goal <130/80 in Diabetic nephropathygoal <130/80 in Diabetic nephropathy– goal <140/80 in other Type 2 DMgoal <140/80 in other Type 2 DM– Probably more realisticProbably more realistic

Microvascular Complications

UKPDSUKPDS 7575

ACE Sartans BBBB I Ca

Insuffisance cardiaque

Nephropathy in DT2

Microalbuminuria

Proteinuria

HVG

DT 2 + HTA

Which Antihypertensive drugs ADA EASD French IDF guidelinesIDF guidelines

DiurTzd Anti-

aldost

VDVDCentralCentral

High CV risk

High CV risk

2ary 2ary prevention

prevention

Prév. 2aireou mal rénale

ou > 10 ans AD+ 2 FR

avec 0 FRavec 0 FRsans micro Angsans micro Ang

< 5 ans d’AD< 5 ans d’AD

Number of RF

LDL-C (g/l)

+ 1 seul FR

< 10 ans AD+ 2 FR

1.9 160160 100100130130

Type 2 DiabetesType 2 Diabetes

French recommendations 2006French recommendations 2006ADA GuidelinesIDF 95 mg/dlIDF 95 mg/dl

CV prevention

STATINSSTATINSVery low risk Very low risk

Low risk Low risk

Medium RiskMedium Risk

High risk High risk ++

2 ary prevention2 ary prevention

Stop Soking

Guidelines

Blood Glucose Control

Microangiopathy and threshold: retinopathy

CV complication and glucose tolerance

0

5

10

15

20

25

30

Normal Intolérance glucose Diabète nondiagnostiqué

débutant

Diabète établi

Normal Intolérance glucose Diabète non diagnostiqué débutant Diabète établi

3174 subjects (30-74 years) 2nd NHANES 1976 - 1980-1990 (% CV death during the follow-up according to glycemic status )

Prof. Serge HALIMI

Myocardial Infarction

Why new recommendations ?Why new recommendations ?

UKDS trial revisited regarding UKDS trial revisited regarding

the design and the conclusionsthe design and the conclusions

Usual strategyUsual strategy

DIet and physical activity

One OAD

Combination of several OADs

Insulin + OADs

Insulin

Adapted from UKPDS 16. Diabetes 1995;44:1249–58

Years from diagnosis

Bet

a-ce

ll f

un

ctio

n (

%)

–10 –8 –6 –4 –2 0 2 46

100

80

60

40

20

0

Beginning of the disease

––1212

How to improve InsSensitivity

How to preventB cell failure

UKPDS worsening of Insulin secretion

Diagnosis

UKPDS : Worsening of Glycated Hb in both groups

(1) U.K. Prospective Diabetes Study Group. Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; Vol 352 : 837-853.

06

7

8

9

0 3 6 9 12 15Years after randomization

« Conventional »

« Intensive »

Why new recommendations ?Why new recommendations ?TThe UKPDS trial Revisited : regarding the design and the he UKPDS trial Revisited : regarding the design and the

conclusions conclusions

• Constant worsening of HbA1c in UKPDS in both Constant worsening of HbA1c in UKPDS in both groupsgroups

• Natural history of the disease (unavoidable) or Natural history of the disease (unavoidable) or consequence of the design of the trial…old consequence of the design of the trial…old strategies !strategies !

• Threshold 7 - 8% for treatment adaptation Threshold 7 - 8% for treatment adaptation (i.e. (i.e. addition of drugs or new regimens)addition of drugs or new regimens) for preventing this for preventing this worsening ?worsening ?

• Deleterious effects of Glucotoxicity Deleterious effects of Glucotoxicity – on Insulin secretionon Insulin secretion– on Insulin resistanceon Insulin resistance– and vascular complicationsand vascular complications

Pivotal role of 3-4 HbA1c measurements/year

7% 8% 7% 8%

64%

75%

Easier is the obstacle (fence) lower jumps the horse

19%19%

43%43%

Probability next > 8%

Probability next > 7%

ConsequencesConsequences

RHD 1 OAD 2 OAD Insulin

8 %

6 %

7 %

3 dimensions

• Metformin as early and as often as possible– Low cost– No hypoglycemia – BW benefit (alone or + OADs or Insulin)– CV prevention ?

• More OADs synergistic associations– Early– Lower thresholds for reinforcement

• New drugs (GTZ)– when well adapted to the patient and – metabolic profile– New target on pathogenesis of T2DM– Allowing for Tritherapy

Why new recommendations ?Why new recommendations ? 2006 consensus 2006 consensus

August 2006August 2006

EASD ADAEASD ADA

IDFIDF

HbA1c Goals HbA1c Goals IDFIDF EASD ADA EASD ADA FrenchFrench guidelines guidelines

Similarities and subtle disagreementsSimilarities and subtle disagreementsEASD ADA 2006 EASD ADA 2006 consensusconsensus

• Try to achieve « near normal glycemia» mainly at the very beginning of the disease

• Goal 7%7% HbA1c for a large majority of type 2 DM patients

• Proposed for all type 2 DM

• Only achieved in 1/3 patients in Europe

IDF GuidelinesIDF Guidelines• Goals range 6-7.5% • Progression from pre-diabetic impaired

glucose tolerance to type 2 diabetes has recently become a target for early intervention with pharmacological agents.

French Guidelines

• Consistent with ADA EASD IDF.• ~ 48% French cohort (ENTRED)

have 7% HbA1c or less• 25% ≤ 6.5%

• Consistent• However the upper limit of the normal

value for HbA1c is 6,1% (+2DS) and not 7%

• For some patients 6.5% HbA1c even 6% would be the goal

EASD ADA Consensus

?

Metformin

Metformin

Metformin

Metformin

Health policy messageHealth policy message 7% 7% for a large majority of patientsfor a large majority of patients

vs < 50% (France< 50% (France))

How to improve type 2 diabetes management for the next 10 years ?

French Guidelines

Lifestyle intervention

> 6.5%> 6.5%

Metformin SU

> 6.5%> 6.5%

No hypo Higher HbA1c rapid action

Metformin

66-6.5%6.5%

No hypo

Metformin

Add SUAdd GTZ

No hypoFast action

few expansive

Add GTZ Metformin

SU

Fast action few expansive

Infrequent association

From 2 OADs to Tritherapy or Insulin

Call to actionCall to action > 7% > 7%

Metformin SUGTZ

No hypo

Metformin

Fast action few expansive

Fast action few expansive

Infrequent association

GTZ SU

Insulin + OADsTritherapyMet + GTZ + Su

Call to actionCall to action

≥≥ 8%8%

Intensive Insulin + Metf± GTZ

Call to action Call to action

> 7%> 7%

1 OAD > 6.5%

For a better management of Type 2 DM

1 OAD : Metformin max dose

Lifestyle Combination

2 OADs

TritherapyMetf+SU+GT

Z

Insulin + OADs

Lifestyle

1 OAD2 OADs

Insulin

7

8

6.5

6

< 6.5%< 6.5% 6.5 % 6.5 % → 8%→ 8%French guidelines 1998French guidelines 199820062006

3 categories of patients 3 categories of patients

Early diagnosed and treatedHyperglycemia = ModerateHyperglycemia = Recent Compliance = GoodMotivation = GoodAvailable = Ther. Resources and therapeutic education

6 – 6.5 %6 – 6.5 %

Late diagnosis or treated More marked hyperglycemiaPoor compliancePoor MotivationFew or no Therapeutic education-tools

7 %7 %

Elderly diabeticsLate appearanceHard contextFew therapeutic resourcesNo valuable glycemicbenefit

>7 % to >7 % to 8%8%

Both Goals and Message to avoid deterioration Both Goals and Message to avoid deterioration

ConclusionConclusionEarly Strong Strict Treatment

• Recommendations are intended to GPs and patientsRecommendations are intended to GPs and patients– Early diagnosis – “don’t consider as minor” slightly elevated HbA1c – Pivotal role of Glycated Hemoglobin – Don’t tolerate deterioration > 3-6 months

• Be strict on the goals as often as possibleBe strict on the goals as often as possible • CombineCombine OADs as soon as possible OADs as soon as possible• Don’t delay the use of insulininsulin• Don’t present it as a threatthreat but as an alternativealternative

treatment• SafetySafety : : consider the benefit/risk of new OADs• CostCost: consider the cost of old and new classes: consider the cost of old and new classes• French guidelines close to IDF but strict +++ Vs ADA-EASDFrench guidelines close to IDF but strict +++ Vs ADA-EASD