DIABETES MELLITUS Guidelines Review

Diabetes Type 2 Management Guidelines:
ADA 21th Conference on Diabetes 2012

April 28, 2012
Jose M. Cabral, MD, FACE
Chair, Department of Endocrinology
cabralj@ccf.org
Disclosures: Jose M. Cabral, MD, FACE

Research & Grant Support:
Lilly
Astra-Zeneca
Speaker Bureau honoraria

Amylin
Boehringer Ingelheim
Sanofi
Diabetes is the epidemic of our

times: 2010 US statistics
28.5 million Americans have diabetes

8.3% of adults have diabetes
1.9 million cases/year
7th leading cause of death
$174 billion is estimated healthcare
expenditure
2050 Prediction: Up to1 out 3 adults with T2DM

CDC - 2011
The Need For Tight Glycemic

Control
According to the United Kingdom Prospective Diabetes
Study (UKPDS) 35, Every 1% Drop in A1C Resulted in:
21%
Decrease
in any
diabetesrelated end
point
14%
12%
37%
Decrease
in risk of MI
Decrease
in risk of
stroke
Decrease
in risk of
microvascular
complications
United Kingdom Prospective Diabetes Study. Stratton IM et al. BMJ. 2000;321:405-412.
Greater Than 50% of Patients With Diabetes

Need Additional Lowering of Cardiovascular
Risk Factors
60
50
40
Patients
Achieving
Goal (%) 30
48.2
44.3
37.0
35.8
29.0
33.9
20
5.2
10
0
A1C
Level <7.0%
Total
Blood
Cholesterol
Pressure
<130/80 mm Hg <200 mg/dL
NHANES III (n=1204)

Adapted from Saydah SH, et al. JAMA. 2004;291:335-342.
7.3
Achieved All 3
Treatment
Goals
NHANES 19992000 (n=370)
Natural History of Type 2 Diabetes

Diagnosis
Prediabetes
Diabetes
Insulin resistance
-Cell
Failure
Endogenous Insulin
Postmeal glucose
Average Time
of Diagnosis
Fasting glucose
Years
Microvascular complications
Macrovascular complications
Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care.
1999;26:771-789
-Cell Function Over Time in Type 2 DM
-Cell Function (%)*
100
75
Patients treated with insulin,

metformin, sulfonylureas
50
25
IGT
0
-12 -10
Type 2
Postprandial
HyperglycemiaDiabetes
Phase I
-6
-2 0
Type 2
Diabetes
Phase II
Type 2
Diabetes
Phase III
10
14
Years From Diagnosis
Adapted from Lebovitz HE. Diabetes Rev. 1999;7:139-153.
Treatment Inertia is a Major Reason for Poor

Patient Response to Therapy :Patients Remain
On Monotherapy >1 Year After First A1C >8.0%
Length of Time Between First
Monotherapy
25 A1C >8.0% and Switch/Addition in
Therapy* 20.5 Months
Months
20
15
14.5 Months
10
5
0
Metformin Only
n = 513
Sulfonylurea Only
n=
3394
Data from Kaiser Permanente Northwest 1994-2002. Patients had to be continuously enrolled for 12 months
with A1C lab values.
Brown JB et al. Diabetes Care. 2004;27:1535-1540.
CAN WE DO BETTER THAN THIS IN TREATING

TYPE 2 DIABETES?
Do we actually know enough to change outcomes?
Have we developed the right tools to use what we know most
effectively?
Have we constructed the right templates and guidelines to
promote timely, appropriate, and effective improvements in
treatment?
Is there sufficient consistency of message to assure reliable or
reasonably reproducible outcomes if the guidelines are
applied?
Are the algorithms we now use beneficial?
Are there any important differences in them?
Are they actually regarded seriously and used?
The Good News.
More therapeutic options

Safer drugs
Improved glucose monitoring devices
Insulin pumps
Artificial pancreas
Discovery of Insulin
Banting and Best
University of Toronto 1921
Diabetes Therapy: The Last 90 years
cells
a cells
cells
a
L cells
1925
1950
1975
2000
Antihyperglycemic Agents for

Type 2 Diabetes
Class
Agents
Sulfonyureas (SU)
Glyburide, glipizide, glimepiride
Meglitinides (Glinide)
Repaglinide, Nateglinide
Metformin (MET)
Metformin
-Glucosidase inhibitor (AGI)
Acarbose, Miglitol
Glitazone (TZD)
Pioglitazone, Rosiglitazone
Incretin mimetics (GLP-1)
Exenatide , Liraglutide
DPP-4 inhibitors (DPP4)
Sitagliptin ,Saxagliptin, Linagliptin
Amylin analogs
Pramlintide
Dopamine agonist (DA)
Bromocriptine mesylate
The Bad News.
Patient-Centered Team Care Model

Patient
Appropriate
Therapy
Behavior
Change
Improved
Outcomes
Provider
&
Staff
Educator
CDE
Standards
of Care
Modified from Bergenstal R, IDC, Minneapolis
President ADA 2010
Patient-Centered Team Care Model

Patient
Appropriate
Therapy
Behavior
Change
Improved
Outcomes
Provider
&
Staff
Educator
CDE
Standards
of Care
Modified from Bergenstal R, IDC, Minneapolis
President ADA 2010
Diabetes Care: Management

People with diabetes should receive medical care
from a physician-coordinated team
Physicians, nurse practitioners, physicians assistants,
nurses, dietitians, pharmacists, mental health
professionals
In this collaborative and integrated team approach,
essential that individuals with diabetes assume an active
role in their care
Management plan should recognize diabetes selfmanagement education (DSME) and on-going
diabetes support
ADA. V. Diabetes Care. Diabetes Care 2012;35(suppl 1):S16.
WHY DO WE NEED OR USE DIABETES Rx

ALGORITHMS IN THE FIRST PLACE?
To reduce the impact of the disease

To alter the natural history of the disease
To reduce the costs of the disease
To translate known scientific insights into
treatment interventions to benefit patients
To reach and maintain treatment goals in
the most efficient and practical way
feasible
Gavin J: ADA 18th Conference, Hollywood, FL
CONSIDERATIONS ON DIABETES TREATMENT

ALGORITHMS: WHY THEY END UP WITH DOWNS
They are guidelines based on available studies
There is an assumption that one-size fits all
The data used for algorithms often reflect few
minorities
They infrequently cover all of the known current needs
to address the spectrum of disease mechanisms in type
2 diabetes, and are often too narrow in scope
Nevertheless, there is some data that many patients
show benefit from use of such guidelines in therapy
The provider must use the algorithms as tools, not as
the solution, thus the algorithm should be holistic
Gavin J: ADA 18th Conference 2009,
Hollywood, FL
ADA/EASD: Managing hyperglycemia

in T2DM
Lifestyle intervention + metformin
If A1C > 7%
Add basal insulin

(most effective)
Add sulfonylurea
(least expensive)
Add glitazone
(no hypoglycemia)
If A1C > 7%
If A1C > 7%
If A1C > 7%
Intensify insulin
Add glitazone
Add basal insulin
If A1C > 7%
Add sulfonylurea
If A1C > 7%
Add basal or intensify insulin

ADA goal: A1C <7%
Intensive insulin + metformin +/- glitazone

Adapted from ADA. Diabetes Care. 2007;30(Suppl 1):S4-41.
2008 ADA/EASD Type 2 Diabetes

Guidelines: Revised Treatment Algorithm
Tier 1: Well-validated core therapies
At diagnosis:
Lifestyle
+
MET
Step 1
Lifestyle + MET
+
Add Basal insulin
Lifestyle + MET
+
Basal/Bolus Insulin
Lifestyle + MET
+
Add Sulfonylurea
Step 2
Step 3
Tier 2: Less-well-validated therapies

Lifestyle + MET
+
Pioglitazone
Lifestyle + MET
+
GLP-1 agonist
Lifestyle + MET
+
Pio + Sulfonylurea
Lifestyle + MET
+
Add Basal insulin
Nathan DM et al. Diabetes Care. 2008;31:173-175.
Based on the staged nature of the

development of T2DM, a step-wise
treatment paradigm has evolved
The scientific assumption has been that specific defects
dominated at certain stages, while the clinical axiom
was to keep treatment simple. There was a high price
to be paid for this exercise in clinical reductionism! We
have failed to truly alter the course and change the
outcome of the disease. Is it possible that our algorithms
have not aligned well with known physiology or made
best use of our tools?
Gavin J: ADA 18th Conference 2009,

Hollywood, FL
Management of Hyperglycemia in Type 2

Diabetes: A Patient-Centered Approach
Position Statement of the American Diabetes Association (ADA) and
the European Association for the Study of Diabetes (EASD)
http://care.diabetesjournals.org/content/early/2012/04/17/dc12-0413.short
http://professional.diabetes.org/ImageBank.aspx
Writing Group
American Diabetes Association
European Assoc. for the Study of Diabetes
Richard M. Bergenstal MD
Intl Diabetes Center, Minneapolis, MN
Michaela Diamant MD, PhD

VU University, Amsterdam, The Netherlands
John B. Buse MD, PhD

University of North Carolina, Chapel Hill, NC
Ele Ferrannini MD
University of Pisa, Pisa, Italy
Anne L. Peters MD
Univ. of Southern California, Los Angeles, CA
Michael Nauck MD
Diabeteszentrum, Bad Lauterberg, Germany
Richard Wender MD
Thomas Jefferson University, Philadelphia, PA
Apostolos Tsapas MD, PhD

Aristotle University, Thessaloniki, Greece
Silvio E. Inzucchi MD (co-chair)

Yale University, New Haven, CT
David R. Matthews MD, DPhil (co-chair)

Oxford University, Oxford, UK
ADA-EASD Position Statement: Management of

Hyperglycemia in T2DM: A Patient-Centered
Approach
1. PATIENT-CENTERED APPROACH
2. BACKGROUND
Epidemiology and health care impact

Relationship of glycemic control to outcomes
Overview of the pathogenesis of Type 2 diabetes
3. ANTI-HYPERGLYCEMIC THERAPY
Glycemic targets
Therapeutic options
- Lifestyle
- Oral agents & non-insulin injectables
- Insulin
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Hyperglycemia in T2DM: A Patient-Centered
Approach
3. ANTIHYPERGLYCEMIC THERAPY
Implementation Strategies
- Initial drug therapy
- Advancing to dual combination therapy
- Advancing to triple combination therapy
- Transitions to and titrations of insulin
4. OTHER CONSIDERATIONS
Age
Weight
Sex/racial/ethnic/genetic differences
Comorbidities (Coronary artery disease, Heart failure,
Chronic kidney disease, Liver dysfunction, Hypoglycemia)
5. FUTURE DIRECTIONS / RESEARCH NEEDS


Hyperglycemia in T2DM
1. Patient-Centered Approach
...providing care that is respectful of and responsive to
individual patient preferences, needs, and values ensuring
that patient values guide all clinical decisions.
Gauge patients preferred level of involvement.

Explore, where possible, therapeutic choices.
Utilize decision aids.
Shared decision making final decisions re: lifestyle
choices ultimately lies with the patient.

2. BACKGROUND
Epidemiology and health care impact
Age-adjusted Percentage of U.S. Adults

with Obesity or Diagnosed Diabetes
Obesity (BMI 30 kg/m2)

1994
O
B
E
S
I
T
Y
Diabetes
D
I
A
B
E
T
E
S
No Data
>26.0%
2000
<14.0%
1994
No Data
>9.0%
14.0-17.9%
2009
18.0-21.9%
2000
<4.5%
4.5-5.9%
22.0-25.9%
2009
6.0-7.4%
7.5-8.9%
CDCs Division of Diabetes Translation. National Diabetes Surveillance System

available at http://www.cdc.gov/diabetes/statistics
The Diabetes Epidemic: Global

Projections, 20102030
IDF. Diabetes Atlas 5th Ed. 2011

2. BACKGROUND
Relationship of glycemic control to

outcomes
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of prin
Impact of Intensive Therapy for Diabetes:

Summary of Major Clinical Trials
Study
Microvasc
UKPDS
DCCT /
EDIC*
ACCORD
ADVANCE
VADT
CVD
Mortality
Kendall DM, Bergenstal RM. International Diabetes Center 2009

UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854.
Holman RR et al. N Engl J Med. 2008;359:1577. DCCT Research Group. N Engl J Med 1993;329;977.
Nathan DM et al. N Engl J Med. 2005;353:2643. Gerstein HC et al. N Engl J Med. 2008;358:2545.
Patel A et al. N Engl J Med 2008;358:2560. Duckworth W et al. N Engl J Med 2009;360:129. (erratum:
Moritz T. N Engl J Med 2009;361:1024)
Initial Trial
Long Term Follow-up
* in T1DM

2. BACKGROUND
Overview of the pathogenesis of T2DM
Insulin secretory dysfunction

Insulin resistance (muscle, fat, liver)
Increased endogenous glucose production
Deranged adipocyte biology
Decreased incretin effect
Main Pathophysiological Defects in T2DM

pancreatic
insulin
secretion
incretin
effect
gut
carbohydrate
delivery &
absorption
pancreatic
glucagon
secretion
HYPERGLYCEMIA
+
hepatic
glucose
production
peripheral
glucose
uptake
Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011

Glycemic targets
HbA1c < 7.0% (mean PG 150-160 mg/dl [8.3-8.9

mmol/l])
Pre-prandial PG <130 mg/dl (7.2 mmol/l)
Post-prandial PG <180 mg/dl (10.0 mmol/l)
Individualization is key:
Tighter targets (6.0 - 6.5%) - younger, healthier
Looser targets (7.5 - 8.0%+) - older, comorbidities,
hypoglycemia prone, etc.
PG = plasma glucose
Avoidance of hypoglycemia
Figure 1

(Adapted with permission from: Ismail-Beigi F, et al. Ann Intern Med 2011;154:554)

Therapeutic options: Lifestyle

- Weight optimization
- Healthy diet
- Increased activity level

Therapeutic options:
Oral agents & non-insulin injectables
- Metformin
- Sulfonylureas
- Thiazolidinediones
- DPP-4 inhibitors
- GLP-1 receptor agonists
- Meglitinides
- a-glucosidase inhibitors
- Bile acid sequestrants
- Dopamine-2 agonists
- Amylin mimetics
Major Targeted Sites of Oral Drug

Classes
Pancreas
Beta-cell
dysfunction
Sulfonylureas
Meglitinides
Liver
DPP-4 inhibitors
GLP-1
Glucose level
Hepatic glucose
overproduction
Insulin
resistance
Gut
Biguanides
TZDs
DPP-4 inhibitors
Glucose
absorption
Muscle
and fat
TZDs
Alphaglucosidase
inhibitors
Biguanides
Biguanides
DeFronzo RA. Ann Intern Med. 1999;131:281303.

Buse JB.: Williams Textbook of Endocrinology. 10th ed. Philadelphia: WB Saunders; 2003:14271483.
Factors to Consider When Selecting

Therapy in Type 2 Diabetes
Degree of
HbA1c
reduction needed
Duration of DM
Contraindications
to agents
MET: Renal, CHF
TZD: CHF
Factors to Consider
When Selecting
Therapy
Potential for
Hypoglycemia
No Hypo:
MET
TZD
AGI
DPP4
GLP-1
Bromocriptine
Body weight
BMI
Obese: MET
DPP4
GLP-1
Bromo
Lean: Glinide
SU
Lipid disorder
MET, TZD
Colesevalam
Postprandial
hyperglycemia
DPP4
Glinide
GLP-1
AGI
Internal Medicine Board Review

2010
Class
Mechanism
Advantages
Disadvantages
Cost
Biguanides
Activates AMP-kinase Extensive experience

No hypoglycemia
Hepatic glucose
production
Weight neutral
? CVD
Gastrointestinal
Lactic acidosis
B-12 deficiency
Contraindications
Low
SUs /
Meglitinides
Closes KATP channels

Insulin secretion
Extensive experience
Microvasc. risk
Hypoglycemia
Weight gain
Low durability
? Ischemic
preconditioning
Low
TZDs
PPAR-g activator
insulin sensitivity
No hypoglycemia
Durability
TGs, HDL-C
? CVD (pio)
Weight gain
Edema / heart
failure
Bone fractures
? MI (rosi)
? Bladder ca (pio)
High
a-GIs
Inhibits aglucosidase
Slows carbohydrate
absorption
No hypoglycemia
Nonsystemic
Post-prandial
glucose
? CVD events
Gastrointestinal
Dosing frequency
Modest A1c
Mod.
Table 1. Properties of anti-hyperglycemic agentsDiabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Class
Mechanism
Advantages
Disadvantages Cost
DPP-4
inhibitors
Inhibits DPP-4
Increases GLP-1, GIP
No hypoglycemia
Well tolerated
Modest A1c
? Pancreatitis
Urticaria
High
GLP-1
receptor
agonists
Activates GLP-1 R
Insulin, glucagon
gastric emptying
satiety
Weight loss
No hypoglycemia
? Beta cell mass
? CV protection
GI
? Pancreatitis
Medullary ca
Injectable
High
Amylin
mimetics
Activates amylin receptor

glucagon
gastric emptying
satiety
Weight loss
PPG
GI
Modest A1c
Injectable
Hypo w/ insulin
Dosing frequency
High
Bile acid
sequestrants
Bind bile acids

Hepatic glucose
production
No hypoglycemia
Nonsystemic
Post-prandial glucose
CVD events
GI
Modest A1c
Dosing frequency
High
Dopamine-2
agonists
Activates DA receptor
Modulates hypothalamic
control of metabolism
insulin sensitivity
No hypoglyemia
? CVD events
Modest A1c
Dizziness/syncope
Nausea
Fatigue
High
Class
Insulin
Mechanism
Advantages
Activates insulin
receptor
peripheral glucose
uptake
Universally
effective
Unlimited efficacy
Microvascular
risk
Disadvantages
Hypoglycemia
Weight gain
? Mitogenicity
Injectable
Training
requirements
Stigma
Cost
Variable

Therapeutic options: Insulin

- Neutral protamine Hagedorn (NPH)
- Regular
- Basal analogues (glargine, detemir)
- Rapid analogues (lispro, aspart, glulisine)
- Pre-mixed varieties

Therapeutic options: Insulin
Insulin level
Rapid (Lispro, Aspart, Glulisine)
Short (Regular)
Intermediate (NPH)
Long (Detemir)
Long (Glargine)
10 Hours
12 14 16
Hours after injection
18
20
22
24

Implementation strategies:
- Initial therapy
- Transitions to & titrations of insulin

Implementation strategies:
- Initial therapy:
- Metformin, if no contraindications
- A1c > 9%: Use 2 non-insulin agents or insulin itself
- If symptoms, BG >300-350, A1c >10-12%, insulin
therapy

- Transitions to & titrations of insulin
Diabetes Care, Diabetologia. 19 April 2012
T2DM Antihyperglycemic Therapy: General Recommendations[Epub ahead of print]
Diabetes Care, Diabetologia.

19 April 2012 [Epub ahead of print]
Sequential Insulin Strategies in T2DM

Age
Weight
Sex / racial / ethnic / genetic differences
Comorbidities
-
Coronary artery disease

Heart Failure
Chronic kidney disease
Liver dysfunction
Hypoglycemia

Age: Older adults
-
Reduced life expectancy

Higher CVD burden
Reduced GFR
At risk for adverse events from polypharmacy
More likely to be compromised from hypoglycemia
Less ambitious targets

HbA1c <7.58.0% if tighter
targets
not easily achieved
Focus on drug safety

Weight
-
Majority of T2DM patients overweight / obese

Intensive lifestyle program
Metformin
GLP-1 receptor agonists
? Bariatric surgery
Consider LADA in lean patients
[Epub ahead of print]

T2DM Anti-hyperglycemic Therapy: General Recommendations
When Goal is to Avoid Weight Gain


Sex/ethnic/racial/genetic differences
- Little is known
- MODY & other monogenic forms of diabetes
- Latinos: more insulin resistance
- East Asians: more beta cell dysfunction
- Gender may drive concerns about adverse effects
(e.g., bone loss from TZDs)

Comorbidities
- Coronary Disease
- Heart Failure
- Renal disease
- Liver dysfunction
- Hypoglycemia
Metformin: CVD benefit
(UKPDS)
Avoid hypoglycemia
? SUs & ischemic
preconditioning
? Pioglitazone & CVD events
? Effects of incretin-based
therapies

Comorbidities
- Coronary Disease
Metformin: May use unless
- Heart Failure
condition is unstable or severe

Avoid TZDs
? Effects of incretin-based
therapies
- Renal disease
- Liver dysfunction
- Hypoglycemia

Comorbidities
- Coronary Disease
- Heart Failure
- Renal disease
- Liver dysfunction
- Hypoglycemia
Most drugs not tested in
advanced liver disease

Pioglitazone may help steatosis
Insulin best option if disease
severe

Comorbidities
- Coronary Disease
- Heart Failure
- Renal disease
- Liver dysfunction
- Hypoglycemia
Emerging concerns regarding
association with increased

mortality
Proper drug selection in the
hypoglycemia prone
T2DM Anti-hyperglycemic Therapy: General Recommendations

[
When Goal is to Avoid Hypoglycemia

When Goal is to Minimize Costs

Guidelines for Glycemic, BP, & Lipid Control

American Diabetes Assoc. Goals
HbA1C
Preprandial
glucose
Postprandial
glucose
Blood pressure
< 7.0% (individualization)

70-130 mg/dL (3.9-7.2 mmol/l)
< 180 mg/dL
< 130/80 mmHg
LDL: < 100 mg/dL (2.59 mmol/l)
< 70 mg/dL (1.81 mmol/l) (with overt CVD)
Lipids
HDL: > 40 mg/dL (1.04 mmol/l)

> 50 mg/dL (1.30 mmol/l)
TG:
HDL = high-density lipoprotein; LDL = low-density
lipoprotein; PG = plasma glucose; TG = triglycerides.
< 150 mg/dL (1.69 mmol/l)

ADA. Diabetes Care. 2012;35:S11-63

KEY POINTS
Glycemic targets & BG-lowering therapies must be individualized.
Diet, exercise, & education: foundation of any T2DM therapy program

Unless contraindicated, metformin = optimal 1st-line drug.
After metformin, data are limited. Combination therapy with 1-2 other
oral / injectable agents is reasonable; minimize side effects.
Ultimately, many patients will require insulin therapy alone / in
combination with other agents to maintain BG control.
All treatment decisions should be made in conjunction with the patient
(focus on preferences, needs & values.)
Comprehensive CV risk reduction - a major focus of therapy.
AACE / ACE Diabetes Algorithm: Principles (1)
Primum non nocere

Stratify treatment based on initial A1C level
Initial monotherapy at A1c 6.57.5; initial dual
therapy 7.69.0; initial triple therapy insulin
>9.0
Monitor A1C carefully and intensify therapy
(monodual, dualtriple insulin) at 2-3 month
intervals if A1c goal not achieved
Combine agents with different mechanisms of
action and different targets of action.
AACE / ACE Diabetes Algorithm: Principles (2)
Consider both safety and effectiveness
Minimize risk of hypoglycemia and weight gain
Individualize therapy for each patient
When other agents fail to achieve goal, progress

to insulin therapy
Major cost of diabetes is due to complications
including hypoglycemia. Emphasize cost of care
not cost of medications
A1C Goal
6.5%
A1C 6.5 7.5%
A1C 7.6 9.0%
A1C > 9.0%

Drug Naive
Symptoms
Monotherapy
MET
DPP4
GLP-1
TZD
AGI
MET
or TZD
Dual Therapy
2 - 3 Mos.
GLP-1 or DPP4
Triple Therapy
TZD
GLP-1
Glinide or SU
TZD
GLP-1 or DPP4
Colesevelam
MET
AGI
2 - 3 Mos.
or DPP4
MET
or DPP4
TZD
Glinide or SU
INSULIN
Other
Agent(s)
GLP-1
or DPP4
MET
SU
INSULIN
Other
Agent(s)
TZD
GLP-1
or DPP4
TZD
+ TZD
GLP-1
+ SU
TZD
2 - 3 Mos.
Triple Therapy
MET +
GLP-1 or
DPP4
Dual or Triple Therapy
GLP-1 or DPP4
SU or Glinide
No Symptoms
Dual Therapy
2 - 3 Mos.
MET
Under Treatment
AGI
-Glucosidase Inhibitor
DPP4 DPP-4 Inhibitor
GLP-1 Incretin Mimetic
Met
Metformin
SU
Sulfonylurea
TZD
Thiazolidinedione
INSULIN
Other
Agent(s)
2 - 3 Mos.
INSULIN
Other
Agent(s)
Adapted and modified from:

Rodbard H, Jellinger P, et al.
Endocrine Practice, 2009 Sept/Oct; 15 (6): 540 559
www.aace.com/pub
A1C Goal
6.5%
A1C 6.5 7.5%
Monotherapy
MET
DPP4
GLP-1
TZD
AGI
2 - 3 Mos.
Dual Therapy
GLP-1 or DPP4
MET
TZD
Glinide or SU
TZD
MET
GLP-1 or DPP4
Colesevelam
AGI
2 - 3 Mos.
Triple Therapy
MET +
GLP-1
or DPP4
TZD
Glinide or SU
2 - 3 Mos.
INSULIN
Other
Agent(s)

Rodbard, H, Jellinger, P, et al.
www.aace.com/pub
A1C Goal
6.5%
A1C 7.6 9.0%
Dual Therapy
GLP-1 or DPP-4
MET
or TZD
SU or Glinide
2 - 3 Mos.
Triple Therapy
GLP-1
or DPP4
MET
+ TZD
GLP-1
or DPP4
+ SU
TZD
2 - 3 Mos.
INSULIN
Other Agent(s)

Rodbard H, Jellinger P, et al.
www.aace.com/pub
A1C > 9.0%
Drug Naive
Symptomatic
Under Treatment
Asymptomatic
Dual or Triple Therapy

GLP-1
or
DPP4
INSULIN
Other
Agent(s)
MET
SU
+ TZD
GLP-1
or
DPP4
INSULIN
Other
Agent(s)
TZD
2 - 3 Mos.
INSULIN
Other Agent(s)
Adapted and modified from: Rodbard H, Jellinger P, et al.

www.aace.com/pub
AGI
-Glucosidase Inhibitor
DPP-4 DPP-4 Inhibitor
GLP-1 Incretin Mimetic
Met
Metformin
SU
Sulfonylurea
TZD
Thiazolidinedione
Thank You !
Questions
Jose M. Cabral, MD
CABRALJ@CCF.ORG
954-659-5271

DIABETES MELLITUS Guidelines Review

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DIABETES MELLITUS Guidelines Review

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Diabetes Type 2 Management Guidelines:

ADA 21th Conference on Diabetes 2012

Disclosures: Jose M. Cabral, MD, FACE

Speaker Bureau honoraria

Diabetes is the epidemic of our

28.5 million Americans have diabetes

2050 Prediction: Up to1 out 3 adults with T2DM

The Need For Tight Glycemic

United Kingdom Prospective Diabetes Study. Stratton IM et al. BMJ. 2000;321:405-412.

Greater Than 50% of Patients With Diabetes

NHANES III (n=1204)

NHANES 19992000 (n=370)

Natural History of Type 2 Diabetes

-Cell Function Over Time in Type 2 DM

-Cell Function (%)*

Patients treated with insulin,

Years From Diagnosis

Adapted from Lebovitz HE. Diabetes Rev. 1999;7:139-153.

Treatment Inertia is a Major Reason for Poor

CAN WE DO BETTER THAN THIS IN TREATING

The Good News.

More therapeutic options

Diabetes Therapy: The Last 90 years

Antihyperglycemic Agents for

Glyburide, glipizide, glimepiride

-Glucosidase inhibitor (AGI)

Incretin mimetics (GLP-1)

DPP-4 inhibitors (DPP4)

Sitagliptin ,Saxagliptin, Linagliptin

Dopamine agonist (DA)

The Bad News.

Patient-Centered Team Care Model

Patient-Centered Team Care Model

Diabetes Care: Management

WHY DO WE NEED OR USE DIABETES Rx

To reduce the impact of the disease

CONSIDERATIONS ON DIABETES TREATMENT

ADA/EASD: Managing hyperglycemia

Add basal insulin

Add basal insulin

Add basal or intensify insulin

Intensive insulin + metformin +/- glitazone

2008 ADA/EASD Type 2 Diabetes

Tier 2: Less-well-validated therapies

Based on the staged nature of the

Gavin J: ADA 18th Conference 2009,

Management of Hyperglycemia in Type 2

European Assoc. for the Study of Diabetes

Michaela Diamant MD, PhD

John B. Buse MD, PhD

Apostolos Tsapas MD, PhD

Silvio E. Inzucchi MD (co-chair)

David R. Matthews MD, DPhil (co-chair)

ADA-EASD Position Statement: Management of

Epidemiology and health care impact

ADA-EASD Position Statement: Management of

5. FUTURE DIRECTIONS / RESEARCH NEEDS

ADA-EASD Position Statement: Management of

Gauge patients preferred level of involvement.

ADA-EASD Position Statement: Management of

Epidemiology and health care impact

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Age-adjusted Percentage of U.S. Adults

Obesity (BMI 30 kg/m2)