diabetes mellitus guidelines review

Diabetes Type 2 Management Guidelines:

ADA 21th Conference on Diabetes 2012April 28, 2012

Jose M. Cabral, MD, FACE

Chair, Department of Endocrinology

[email protected]

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

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

The Need For Tight GlycemicControl

According to the United Kingdom Prospective DiabetesStudy (UKPDS) 35, Every 1% Drop in A1C Resulted in:

Decrease in risk of

microvascularcomplications

Decrease in any

diabetes-related end

point

Decreasein risk of MI

Decrease in risk of

stroke

21%14% 12%

37%

Greater Than 50% of Patients With Diabetes Need Additional Lowering of Cardiovascular Risk Factors

NHANES III (n=1204) NHANES 19992000 (n=370)

Adapted from Saydah SH, et al. JAMA. 2004;291:335-342.

44.3

29.033.9

5.2

37.0 35.8

48.2

7.3

0

10

20

30

40

50

60

A1CLevel

Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care.

1999;26:771-789

Insulin resistance

Endogenous Insulin

Fasting glucose

Natural History of Type 2 Diabetes

Microvascular complications

Postmeal glucose

Macrovascular complications

Prediabetes Diabetes

-Cell Failure

Average Time of Diagnosis

Diagnosis

Microvascular complicationsMacrovascular complicationsYears

-C

ell F

unct

ion

(%)*

PostprandialHyperglycemia

IGT Type 2DiabetesPhase I Type 2

DiabetesPhase II

Type 2 DiabetesPhase III

25

100

75

0

50

-12 -10 -6 -2 0 2 6 10 14

Years From Diagnosis

Patients treated with insulin, metformin, sulfonylureas

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

-Cell Function Over Time in Type 2 DM

Treatment Inertia is a Major Reason for Poor Patient Response to Therapy :Patients Remain On Monotherapy >1 Year After First A1C >8.0%

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.

0

5

10

15

20

25

Metformin Only Sulfonylurea Only

Mon

ths

n = 513 n = 3394

14.5 Months

20.5 Months

Length of Time Between First Monotherapy

A1C >8.0% and Switch/Addition in Therapy*

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 BestUniversity of Toronto 1921

Diabetes Therapy: The Last 90 years

cells

1925 200019751950

a cells

L cells

Diabetes Therapy: The Last 90 years

cells

1925 20001975

a cells

L cells

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

Improved Outcomes

EducatorCDE

Provider &

Staff

Patient

Standardsof Care

AppropriateTherapy

Behavior Change

Modified from Bergenstal R, IDC, MinneapolisPresident ADA 2010

ADA. V. Diabetes Care. Diabetes Care 2012;35(suppl 1):S16.

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 self-management education (DSME) and on-going diabetes support

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

Adapted from ADA. Diabetes Care. 2007;30(Suppl 1):S4-41.

Lifestyle intervention + metformin

If A1C > 7%

Add sulfonylurea(least expensive)

Add basal insulin(most effective)

Add glitazone(no hypoglycemia)

Add basal or intensify insulin

Intensive insulin + metformin +/- glitazone

If A1C > 7% If A1C > 7%

Intensify insulin Add glitazone Add basal insulin Add sulfonylurea

If A1C > 7%If A1C > 7% If A1C > 7%

ADA goal: A1C

2008 ADA/EASD Type 2 Diabetes Guidelines: Revised Treatment Algorithm

Lifestyle + MET

+

GLP-1 agonist

Lifestyle + MET+

Basal/Bolus Insulin

Lifestyle + MET

+

Pioglitazone

At diagnosis:

Lifestyle+

MET

Lifestyle + MET+

Add Basal insulin

Lifestyle + MET+

Add Sulfonylurea

Step 1 Step 2 Step 3

Tier 2: Less-well-validated therapies

Tier 1: Well-validated core therapies

Lifestyle + MET+

Add Basal insulin

Lifestyle + MET+

Pio + Sulfonylurea

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

Richard M. Bergenstal MDIntl Diabetes Center, Minneapolis, MN

John B. Buse MD, PhDUniversity of North Carolina, Chapel Hill, NC

Anne L. Peters MDUniv. of Southern California, Los Angeles, CA

Richard Wender MDThomas Jefferson University, Philadelphia, PA

Silvio E. Inzucchi MD (co-chair)Yale University, New Haven, CT

European Assoc. for the Study of Diabetes

Michaela Diamant MD, PhDVU University, Amsterdam, The Netherlands

Ele Ferrannini MDUniversity of Pisa, Pisa, Italy

Michael Nauck MDDiabeteszentrum, Bad Lauterberg, Germany

Apostolos Tsapas MD, PhDAristotle University, Thessaloniki, Greece

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]

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: A Patient-Centered

Approach



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)

Diabetes

1994

1994

2000

2000

No Data 26.0%

No Data 9.0%

CDCs Division of Diabetes Translation. National Diabetes Surveillance System

available at http://www.cdc.gov/diabetes/statistics

2009

2009

O

BESITY

DIABETES

The Diabetes Epidemic: Global Projections, 20102030

IDF. Diabetes Atlas 5th Ed. 2011



2. BACKGROUND

Relationship of glycemic control to outcomes


Impact of Intensive Therapy for Diabetes: Summary of Major Clinical Trials

Study Microvasc CVD Mortality

UKPDS DCCT / EDIC*

ACCORD ADVANCE

VADT

Long Term Follow-up

Initial Trial

* in T1DM

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)



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


+-

-

peripheralglucose uptake

hepatic glucose production

pancreatic insulinsecretion

pancreatic glucagonsecretion

Main Pathophysiological Defects in T2DM

gutcarbohydratedelivery &absorption

incretineffect

HYPERGLYCEMIA

?

Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011



3. ANTI-HYPERGLYCEMIC THERAPY

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

mmol/l])

- Pre-prandial PG

Figure 1 Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print](Adapted with permission from: Ismail-Beigi F, et al. Ann Intern Med 2011;154:554)




Therapeutic options: Lifestyle

- Weight optimization

- Healthy diet

- Increased activity levelDiabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]




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


Glucose absorption

Hepatic glucoseoverproduction

Beta-celldysfunction

Insulinresistance

Major Targeted Sites of Oral Drug Classes

DeFronzo RA. Ann Intern Med. 1999;131:281303. Buse JB.: Williams Textbook of Endocrinology. 10th ed. Philadelphia: WB Saunders; 2003:14271483.

Pancreas

Glucose level

Muscle and fatLiver

Biguanides

TZDs Biguanides

Sulfonylureas

Meglitinides

TZDs

Alpha-glucosidase inhibitors

Gut

DPP-4 inhibitorsGLP-1

DPP-4 inhibitors

Biguanides

Internal Medicine Board Review 2010

Factors to Consider When Selecting Therapy in Type 2 Diabetes

Factors to Consider When Selecting

Therapy

Degree of

HbA1c

reduction needed

Duration of DM

Potential forHypoglycemia

Contraindications to agents

Body weight BMI

Lipid disorder

Postprandial hyperglycemia

No Hypo:METTZDAGIDPP4GLP-1Bromocriptine

MET, TZDColesevalam

DPP4GlinideGLP-1AGI

Obese: METDPP4GLP-1Bromo

Lean: GlinideSU

MET: Renal, CHFTZD: CHF

Class Mechanism Advantages Disadvantages Cost

Biguanides Activates AMP-kinase Hepatic glucose production

Extensive experience No hypoglycemia 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 / heartfailure Bone fractures ? MI (rosi) ? Bladder ca (pio)

High

a-GIs Inhibits a-glucosidase Slows carbohydrate absorption

No hypoglycemia Nonsystemic Post-prandialglucose ? 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 CostDPP-4inhibitors

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

Amylinmimetics

Activates amylin receptor glucagon gastric emptying satiety

Weight loss PPG

GI Modest A1c Injectable Hypo w/ insulin Dosing frequency

High

Bile acidsequestrants

Bind bile acids Hepatic glucose production

No hypoglycemia Nonsystemic Post-prandial glucose CVD events

GI Modest A1c Dosing frequency

High

Dopamine-2agonists

Activates DA receptor Modulates hypothalamic control of metabolism insulin sensitivity

No hypoglyemia ? CVD events

Modest A1c Dizziness/syncope Nausea Fatigue

High


Class Mechanism Advantages Disadvantages Cost

Insulin Activates insulin receptor peripheral glucose uptake

Universallyeffective Unlimited efficacy Microvascularrisk

Hypoglycemia Weight gain ? Mitogenicity Injectable Training requirements Stigma

Variable





Therapeutic options: Insulin- Neutral protamine Hagedorn (NPH)

- Regular

- Basal analogues (glargine, detemir)

- Rapid analogues (lispro, aspart, glulisine)

- Pre-mixed varieties




Long (Detemir)

Rapid (Lispro, Aspart, Glulisine)

Hours

Long (Glargine)

0 2 4 6 8 10 12 14 16 18 20 22 24

Short (Regular)

Hours after injection

Insu

lin le

vel


Therapeutic options: Insulin

Intermediate (NPH)




Implementation strategies:- Initial therapy

- Advancing to dual combination 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

- Advancing to dual combination therapy


- Transitions to & titrations of insulinDiabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

T2DM Antihyperglycemic Therapy: General RecommendationsDiabetes Care, Diabetologia. 19 April 2012

[Epub ahead of print]

Diabetes Care, Diabetologia.

19 April 2012 [Epub ahead of print]

Sequential Insulin Strategies in T2DM Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]



4. OTHER CONSIDERATIONS

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




Weight- Majority of T2DM patients overweight / obese- Intensive lifestyle program- Metformin- GLP-1 receptor agonists- ? Bariatric surgery- Consider LADA in lean patients


T2DM Anti-hyperglycemic Therapy: General RecommendationsDiabetes Care, Diabetologia. 19 April 2012

[Epub ahead of print]

When Goal is to Avoid Weight GainDiabetes Care, Diabetologia. 19 April 2012




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






- Heart Failure

- Renal disease

- Liver dysfunction

- Hypoglycemia

Metformin: May use unless condition is unstable or severe

Avoid TZDs

? Effects of incretin-based therapies






- 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






- Heart Failure

- Renal disease

- Liver dysfunction

- Hypoglycemia Emerging concerns regarding

association with increasedmortality

Proper drug selection in the hypoglycemia prone


T2DM Anti-hyperglycemic Therapy: General RecommendationsDiabetes Care, Diabetologia. 19 April 2012

[

When Goal is to Avoid HypoglycemiaDiabetes Care, Diabetologia. 19 April 2012

When Goal is to Minimize CostsDiabetes Care, Diabetologia. 19 April 2012

Guidelines for Glycemic, BP, & Lipid Control

American Diabetes Assoc. Goals

HbA1C < 7.0% (individualization)

Preprandial glucose

70-130 mg/dL (3.9-7.2 mmol/l)

Postprandial glucose

< 180 mg/dL

Blood pressure < 130/80 mmHg

Lipids

LDL: < 100 mg/dL (2.59 mmol/l)

< 70 mg/dL (1.81 mmol/l) (with overt CVD)

HDL: > 40 mg/dL (1.04 mmol/l)

> 50 mg/dL (1.30 mmol/l)

TG: < 150 mg/dL (1.69 mmol/l)

ADA. Diabetes Care. 2012;35:S11-63HDL = high-density lipoprotein; LDL = low-density lipoprotein; PG = plasma glucose; TG = triglycerides.



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.

Consider both safety and effectiveness

Minimize risk of hypoglycemia and weight gain

When other agents fail to achieve goal, progress to insulin therapy

Individualize therapy for each patient

Major cost of diabetes is due to complications including hypoglycemia. Emphasize cost of care not cost of medications

AACE / ACE Diabetes Algorithm: Principles (2)

A1C 6.5 7.5%

Monotherapy

2 - 3 Mos.

2 - 3 Mos.

2 - 3 Mos.

Dual Therapy

MET +

GLP-1 or DPP4

or TZD

SU or Glinide

A1C 7.6 9.0%

Dual Therapy

2 - 3 Mos.

2 - 3 Mos.

Triple Therapy

MET +GLP-1 or DPP4

+TZD

Glinide or SU

MET +

GLP-1

or DPP4+ TZD

GLP-1

or DPP4 + SU

TZD

A1C > 9.0%

No Symptoms

Drug Naive Under Treatment

INSULIN Other Agent(s)

Symptoms




Triple Therapy

AGI -Glucosidase InhibitorDPP4 DPP-4 InhibitorGLP-1 Incretin MimeticMet MetforminSU SulfonylureaTZD Thiazolidinedione

A1C Goal 6.5%

Adapted and modified from:

Rodbard H, Jellinger P, et al. Endocrine Practice, 2009 Sept/Oct; 15 (6): 540 559www.aace.com/pub

MET +

GLP-1

or DPP4 SU

TZD

GLP-1

or DPP4 TZD

MET DPP4 GLP-1 TZD AGI Dual or Triple Therapy

MET +

GLP-1 or DPP4

TZD

Glinide or SU

TZD + GLP-1 or DPP4

MET +Colesevelam

AGI

A1C 6.5 7.5%

Monotherapy

2 - 3 Mos.

2 - 3 Mos.

2 - 3 Mos.

Dual Therapy

MET +GLP-1 or DPP4

+TZD

Glinide or SU


Triple Therapy

A1C Goal 6.5%

MET DPP4 GLP-1 TZD AGI


Rodbard, H, Jellinger, P, et al. Endocrine Practice, 2009 Sept/Oct; 15 (6): 540 559www.aace.com/pub

MET +

GLP-1 or DPP4

TZD

Glinide or SU

TZD + GLP-1 or DPP4

MET +Colesevelam

AGI

MET +

GLP-1 or DPP-4

or TZD

SU or Glinide

A1C 7.6 9.0%

Dual Therapy

2 - 3 Mos.

2 - 3 Mos.

Triple Therapy

MET +

GLP-1

or DPP4+ TZD

GLP-1

or DPP4 + SU

TZD


A1C Goal 6.5%


Rodbard H, Jellinger P, et al. Endocrine Practice, 2009 Sept/Oct; 15 (6): 540 559www.aace.com/pub

A1C > 9.0%

Asymptomatic

Drug Naive Under Treatment


Symptomatic


AGI -Glucosidase Inhibitor DPP-4 DPP-4 InhibitorGLP-1 Incretin MimeticMet MetforminSU SulfonylureaTZD Thiazolidinedione

Adapted and modified from: Rodbard H, Jellinger P, et al. Endocrine Practice, 2009 Sept/Oct; 15 (6): 540 559

www.aace.com/pub

MET +

GLP-1or DPP4 SU

TZD

GLP-1or DPP4

TZD

Dual or Triple Therapy


2 - 3 Mos.

Thank You !

Questions

Jose M. Cabral, [email protected]

954-659-5271

diabetes mellitus guidelines review

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