27 - jul - 2010

GUIDELINES??????WHY & HOW

DRMohammad AL- SALEH

Endocrinologist -Diabetologist

اكتشاف االكتشافاِت كان أعظَم األنسولينالحديث العصر في أدنى الطبية بال كان لكنَّه

. أهمها من واحداً شكفراغ من يتأتَّ لْم .ويقيناً

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. األخرى المجاالت

PREVALENCE ESTIMATES OF DIABETES, 2025

THE WORLD AT A GLANCE

2007 2025Total population 6.6 billion 7.9 billionAdult population (20-79 years) 4.1 billion 5.2 billion

DIABETES (20-79 years)Comparative prevalence 6.0 % 7.3 %Number of people with diabetes 246 million 380 million

IGT (20-79 years)Comparative prevalence 7.5 % 8.0 %Number of people with IGT 308 million 418 million

“I’m going to increase the dose of those tablets you aren’t taking”

practitioners are often left without a clear pathway of therapy to follow.We developed the following consensus approach to the management of hyperglycemia in the adult to help guide health care providers in choosing the most appropriate interventions for their patients with type 2 diabetes.

clinical judgement, that is, our collective knowledge and clinical experience, which takes into account benefits, risks, and costs in the treatment of diabetes.

As in all clinical decision making, an evidence-based review of the literature must also be supplemented by value judgements, where the benefits of treatment are weighed against risks and costs in a subjective fashion.

the clinical trials that address the effectiveness and safety of the different modalities of therapy

sources

The epidemic of type 2 diabetes and the recognition that achieving specific glycemic goals can substantially reduce morbidity have made the effective treatment of hyperglycemia a top priority

therapies directed at other coincident features, such as dyslipidemia, hypertension, hypercoagulability, obesity, and insulin resistance, have also been a major focus of research and therapy

Maintaining glycemic levels as close to the nondiabetic range as possible has been demonstrated to have a powerful beneficial effect on diabetes-specific microvascular complications, including retinopathy, nephropathy, and neuropathy, in the setting of type 1 diabetes in type 2 diabetes, more intensive treatment strategies have likewise been demonstrated to reduce microvascular complications

Why Guidelines are Issued:

The Angelic versionpractitioners are often left without a clear pathway of therapy to follow.We developed the following consensus approach to the management of hyperglycemia in the adult to help guide health care providers in choosing the most appropriate interventions for their patients with type 2 diabetes.Guidelines help doctors to offer the best, safest and most cost-effective treatment to their patients.

They are issued as a service to humanity

Is the ADA/EASD algorithm for the management of type 2diabetes (January 2009) based on evidence or opinion?A critical analysisG. Schernthaner & A. H. Barnett & D. J. Betteridge & R. Carmena & A. Ceriello &B. Charbonnel &M. Hanefeld & R. Lehmann & M. T. Malecki & R. Nesto & V. Pirags &A. Scheen & J. Seufert & A. Sjohölm & A. Tsatsoulis & R. DeFronzo

According to Nathan et al., glucose-lowering efficacy is the principal factor by which drugs should be differentiated.Their algorithm states that ‘The over-archingprinciple in selecting a particular intervention will be its ability to achieve and maintain glycaemic goals

Glucose-lowering effects

Summary: glucose-lowering effects and a re-evaluation of the ADA/EASD algorithm

• In the short term (<1 year), the glucose-lowering efficacy of monotherapy with metformin,sulfonylureas or thiazolidinediones (and probably glinides and incretin-based therapies) is similar and may not be a compelling factor on which to base treatment choice. As such, other advantages/disadvantages of these agents (e.g. hypoglycaemia risk, weight gain) should be afforded greater importance within the limits of approved indications .

• More consideration should be given to long-term glucose control, including use of individual therapies or combinations with more sustained glucose-lowering effects.

• Metformin and sulfonylureas, recommended by Nathan et al. as Tier 1 agents, are inexpensive and improve short-term glycaemic control, but sulfonylureas in particular are associated with progressive treatment failure and may not be the most appropriate choice over the long term.

• The optimal approach to add-on (or indeed initial) insulin therapy remains unclear and should not be restricted solely to consideration of basal insulin therapy.

Summary: other pathophysiological and clinical effects and a re-evaluation of the ADA/EASD

algorithm• In the absence of primary endpoint outcomes data, consideration of the impact of individual glucose lowering drugs on cardiovascular risk factors/markers and measures of atherosclerosis progression isWarranted.

• As the progressive decline in beta cell function is a key factor limiting long-term glycaemic control, more consideration should be given to drugs with beta cell-preserving properties (preferably alongside clinical evidence for durable glycaemic control).

• The complex benefit−safety profiles of individual glucose-lowering agents highlight the need for individualised therapy in the pathophysiologically complex and heterogeneous type 2 diabetespopulation

Summary: cardiovascular benefit−risk relations and a re-evaluation of the ADA/EASD algorithm

• Due to the high risk of macrovascular events in type 2 diabetes and absence of any well-established macrovascular benefit for glucose-lowering as such, more consideration should be given to the macrovascular benefit−risk profiles of individual glucose-lowering therapies. At present, there is good evidence of benefit for metformin (as initial therapy) in primary prevention and for pioglitazone (as part of guideline-driven therapy) in secondary prevention.

• Special emphasis on metformin/sulfonylurea as the combination of choice is questionable in the absence of any outcomes data and considering evidence of a potential adverse impact on outcomes.

The Satanic version

Guidelines are a statement of authority

They assert the right of competing organizations to legislate for the diabetes

community

Guidelines are a Statement of Authority

Do you doubt this assertion?

Then ask yourself this question:

Are guidelines judged according to their scientific quality?

or according to the status of the organization that issued them?

1. Ontological2. Territorial3. Imperial

There are 3 types of guideline:

The Ontological Guideline:

“I think, therefore I exist”

René Descartes

“We issue guidelines, therefore we are important”

Any professional organisation

The Territorial GuidelineThe IDF

will define the

metabolic syndrome

and diabetes

No, EASD and ADA will!

The Imperial GuidelineReclassifies previously unconsidered biological

variation as disease.

Guidelines Extend Disease

PRE - PRE - PRE - PRE………………

Examples:Hypertension: “Prehypertension”Diabetes: “Prediabetes”Cardiology: The NSTEMIHepatology: Fatty liver to NAFLD

Nephrology: Reduced GFR of ageing becomes CKD!

“All individuals with a Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for 3 months are classified as having chronic kidney disease, irrespective of the presence or absence of kidney damage..

Nephrology: Reduced GFR of ageing becomes CKD!

Guidelines do not set out to reduce the boundaries of disease

They set out to increase it

Consensus

“When people can’t agree about something, they reach a consensus”Margaret Thatcher

“What the majority of people sitting around a table would prefer to believe”

Edwin Gale

The Therapeutic Imperative

By extending the boundaries of disease, guidelines also extend the boundaries of treatment…

Guidelines try to define the ideal therapy rather

than the optimal therapy

Guidelines generally ignore

adverse events

Physicians overestimate the benefit of interventions upon survival

UKPDS PhysiciansCase 1 Before 5.1 6.9 yrs

After 5.9 11.5 yrsCase 2 Before 9.3 11.8 yrs

After 9.4 19 yrs

Case 3 Before 10.7 9.8 yrsAfter 10.9 17 yrs

Patel et al, Diabetic Med (2009) 26:453-4

Least worst diabetes management?

“When one admits that nothing is certain, one must, I think, also add that some things

are much more nearly certain than others”Bertrand Russell

Somemore certain conclusions

1.Glucose control strongly influences the risk of microvascular complications, but the benefits diminish with age.

2.Glucose control is more valuable in primary than secondary prevention of vascular outcomes

Somemore

certain conclusions

1. Some therapies (e.g. metformin) may be more effective for CVD than others with similar glucose-lowering properties

2. Glucose targets below HbA1c 8% represent a good therapeutic compromise in most older patients.

3. But we should treat biological age, not chronological age.

1. More therapeutic effort should be directed to those with HbA1c levels >8%

2. But we should acknowledge that the limitations to good glucose control are more behavioral than pharmacological …

Somemore

certain conclusions

“One size fits all” recommendations may be OK for populations.But each person who comes to us is unique“People do not have outcomes. A person is an outcome”

Somemore

certain conclusions

There are two type of Diabetologist:

Type 1 and Type 2

Type 1 diabetologists treat diabetes

Type 2 diabetologists treat people who have diabetes

Millions

NUMBER OF PEOPLE WITH DIABETES BY AGE GROUP, 2007 AND 2025

Decisions About Intensity of Glycemic Control Should Depend on Age and Functional Status

Huang ES, Zhang Q, Gandra N, Chin MH, Meltzer DO: The effect of comorbid illness and functional status on the expected benefits of intensive glucose control in older patients with type 2 diabetes: a decision analysis. Ann Intern Med 149:11-19, 2008

Decisions about intensive glycemic control in older adults should consider life expectancy, which can be assessed based on age and functional status. Older adults with limited life expectancy are unlikely to benefit from intensive control compared with moderate control.

Conclusions

Results. The potential benefits of intensive glycemic control were relatively small (51-116 quality-adjusted life-days gained) and appeared to depend on age and the presence of functional disability. When life expectancy was < 5 years, intensive control produced little benefit, even under optimistic assumptions.