Clinical Guidelines for Treatment of Type 2 Diabetes

Clinical Guidelines for Treatment of Type 2 Diabetes

Carol H. Wysham, MDClinical Associate Professor of Medicine

University of WashingtonSection Head, Rockwood Center for Diabetes and Endocrinology

Disclosure Information

• Consultant: Amylin Pharmaceuticals, Boerhinger Ingelheim, Eli Lilly & Co, Johnson and Johnson, Sanofi U.S.

• Research funding (paid to institution): Amylin Pharmaceuticals, Boerhinger Ingelheim, Eli Lilly & Co, Intarcia, Johnson and Johnson, Merck, NovoNordisk, Sanofi U.S.

• Speakers Bureau: Amylin Pharmaceuticals, Boerhinger Ingelheim, Eli Lilly & Co, Johnson and Johnson, Merck, NovoNordisk, Sanofi U.S.

Age-adjusted Percentage of U.S. Adults With Obesity or Diagnosed Diabetes

Obesity (BMI ≥30 kg/m2)

Diabetes

1994

1994

2000

2000

No Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% >26.0%

No Data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% >9.0%

2009

2009

CDC Diabetes Data & Trends. National Surveillance Date. http://www.cdc.gov/diabetes/statistics. Accessed 2/8/12.

The Diabetes Epidemic: Global Projections, 2010–2030

IDF. Diabetes Atlas 5th Ed. 2011

ADA/EASD Revised Consensus Statement (2009)

David Nathan et al. Diabetes Care 2009; 32:193-203

Tier 1 : Well-validated core therapies

At diagnosis:

Lifestyle+

Metformin

Step 1

Lifestyle + Metformin+

Intensive Insulin

Step 3


PioglitazoneNo hypglycemiaOedema/CHF

Bone loss


GLP-1 agonistb

No hypglycemiaWeight loss

Nausea/Vomitting


Pioglitazone+

Sulphonylureas


Basal insulin

Tier 2 : Less well-validated core therapies


Basal Insulin


Sulphonlyureasa

Step 2

a A Sulphonylurea other than Glibenclamide or Chlorpropamide b Insufficient clinical use to be confident regarding safety.

Critical Question following the „ADA-EASD- Consensus“

• Should all patients be treated following an identical algorythm irrespective of their age, co-morbidity, beta- cell function, insulin-resistant state, and risk for hypoglycemia?

• Most likely not, since type 2 diabetes is a rather hereogenous disease

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)

Diabetes Care 2012;35:1364–1379Diabetologia 2012;55:1577–1596

Writing Group

American Diabetes Association

Richard M. Bergenstal MDInt’l 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

Invited Reviewers

Professional Practice Committee, American Diabetes AssociationPanel for Overseeing Guidelines and Statements, European Association for the Study of Diabetes

American Association of Diabetes EducatorsThe Endocrine Society

American College of Physicians

James Best, The University of Melbourne, AustraliaHenk Bilo, Isala Clinics, Zwolle, NetherlandsJohn Boltri, Wayne State University, Detroit, MIThomas Buchanan, Univ of So California, LA, CAPaul Callaway, University of Kansas,Wichita, KSBernard Charbonnel, University of Nantes, France Stephen Colagiuri, The University of Sydney, AustraliaSamuel Dagogo-Jack, Univ of Tenn, Memphis, TNMargo Farber, Detroit Medical Center, Detroit, MI Cynthia Fritschi, University of Illinois, Chicago, IL Rowan Hillson, Hillingdon Hospital, Uxbridge, U.K.Faramarz Ismail-Beigi, CWR Univ, Cleveland, OH Devan Kansagara, Oregon H&S Univ, Portland, OR

Ilias Migdalis, NIMTS Hospital, Athens, Greece

Donna Miller, Univ of So California, LA, CA

Robert Ratner, MedStar/Georgetown Univ, DC

Julio Rosenstock, Dallas Diab/Endo Ctr, Dallas, TX

Guntram Schernthaner, Rudolfstiftung Hosp, Vienna, Austr

Robert Sherwin, Yale University, New Haven, CT

Jay Skyler, University of Miami, Miami, FL

Geralyn Spollett, Yale University, New Haven, CT

Ellie Strock, Int’l Diabetes Center, Minneapolis, MN

Agathocles Tsatsoulis, University of Ioannina, Greece

Andrew Wolf, Univ of Virginia Charlottesville, VA

Bernard Zinman, University of Toronto, Ontario, Canada

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


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



ADA‐EASD Position Statement: Management of 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 patient’s preferred level of involvement.

• Explore, where possible, therapeutic choices.

• Utilize decision aids.

• Shared decision making – final decisions re: lifestyle choices ultimately lie with the patient.


Informed Medical Decision

22% of U.S. patients take less of the medication than is prescribed

American Heart Association: Statistics you need to know. http://www.americanheart.org/presenter.jhtml?identifier=107

Accessed November 21, 2007.

Medication Adherence

Why Don’t Patients Adhere to Their Medication Therapy?

Side effects

Dosing frequency

Complex regimen

Failure to explain benefits and side effects of medications

Failure of the provider to understand cost of treatment

Having a poor therapeutic relationshipwith patient

Benner JS, Glynn RJ, Mogun H, Neumann PJ, Weinstein MC, Avorn J. Long‐term persistence in use of statin

therapy in elderly patients. JAMA 2002;288:455‐461

Osterberg L, et al. N Engl J Med. 2005;353:487‐497.

Patient satisfaction with their health care provider


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. Kendall DM, Bergenstal RM. ©© International Diabetes Center 2009International Diabetes Center 2009UK 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)

++

Peripheralglucose uptake Hepatic

glucose production

Pancreatic Insulin/amylinsecretion

Pancreatic glucagonsecretion

Main Pathophysiological Defects in Type 2 Diabetes

Gutcarbohydratedelivery &absorption

Incretineffect

HyperglycemiaHyperglycemia ?

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 <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.

- Avoidance of hypoglycemia

PG = plasma glucose Diabetes Care 2012;35:1364–1379Diabetologia 2012;55:1577–1596

Figure 1Diabetes Care 2012;35:1364–1379

Diabetologia 2012;55:1577–1596(Adapted with permission from: Ismail-Beigi 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

‐glucosidase inhibitors ‐ Bile acid sequestrants‐ Dopamine‐2 agonists

‐ Amylin mimetics



ClassClass MechanismMechanism AdvantagesAdvantages DisadvantagesDisadvantages CostCostBiguanides(Metformin)

• Activates AMP‐ kinase• Hepatic glucose production

• Extensive experience• No hypoglycemia• Weight neutral• ? CVD events

• Gastrointestinal• Lactic acidosis• B‐12 deficiency• Contraindications

Low

SUs / Meglitinides

• Closes KATP channels• Insulin secretion

• Extensive experience• Microvascular risk

• Hypoglycemia• Weight gain• Low durability• ? Ischemic preconditioning

Low

TZDs • Activates PPAR‐• Insulin sensitivity

• No hypoglycemia• Durability• TGs, HDL‐C • ? CVD events (pio)

• Weight gain• Edema / heart failure• Bone fractures• ? MI (rosi)• ? Bladder ca (pio)

High

‐GIs • Inhibits ‐ glucosidase• Slows carbohydrate absorption

• No hypoglycemia• Nonsystemic• Post‐prandial glucose• ? CVD events

• Gastrointestinal• Dosing frequency• Modest A1c

Mod.


ClassClass MechanismMechanism AdvantagesAdvantages DisadvantagesDisadvantages CostCostDPP‐4inhibitors

• Inhibits DPP‐4• Increases GLP‐1, GIP

• No hypoglycemia• Well tolerated

• Modest A1c • ? Pancreatitis• Urticaria

High

GLP‐1 receptor agonists

• Activates GLP‐1 receptor• 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• Post‐prandial glucose

• GI• Modest A1c • Injectable• Hypo w/ insulin• Dosing frequency

High

Bile acid sequestrant s

• Binds bile acids• Hepatic glucose production

• No hypoglycemia• Nonsystemic• LDL‐C

• GI• Modest A1c• TGs• Dosing frequency

High

Dopamine‐2agonists

• Activates DA receptor• Modulates hypothalamic control of metabolism• Insulin sensitivity

• No hypoglycemia• ? CVD events

• Modest A1c• Dizziness/syncope• Nausea• Fatigue

High

ClassClass MechanismMechanism AdvantagesAdvantages DisadvantagesDisadvantages CostCostInsulin • Activates insulin

receptor• Glucose disposal• Hepatic glucose production

• Universally effective• Unlimited efficacy• Microvascular risk

• Hypoglycemia• Weight gain• ? Mitogenicity• Injectable• Training requirements• “Stigma”

Variabl e

Table 1. Properties of anti‐hyperglycemic agentsDiabetes Care 2012;35:1364–1379

Diabetologia 2012;55:1577–1596


• Therapeutic options: Insulin

‐ Human Neutral protamine Hagedorn (NPH)

‐ Human Regular

‐ Basal analogues (glargine, detemir)

‐ Rapid analogues (lispro, aspart, glulisine)

‐ Pre‐mixed varieties




• Therapeutic options: Insulin

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

Insulin

level

Intermediate (NPH)


Fig. 3. Sequential Insulin Strategies in T2DM Diabetes Care 2012;35:1364–1379Diabetologia 2012;55:1577–1596


• Implementation strategies:

- Initial therapy- Advancing to dual combination therapy

- Advancing to triple combination therapy

- Transitions to & titrations of insulin



SulfonylureasSulfonylureas GlinidesGlinides

Liver

Pancreas

aa‐‐Glucosidase InhibitorsGlucosidase Inhibitors

Bile acid sequestrantsBile acid sequestrants

Gut

Muscle

HyperglycemiaHyperglycemia

AdiposeTissue

Therapy for Type 2 Diabetes: Sites of Action

DPPDPP--IV IV inhibitors inhibitors

Insulin

Insulin Insulin

GLP-1Ra

GLP-1Ra

GLP-1Ra

GlitazonesGlitazones

GlitazonesGlitazones

GlitazonesGlitazonesBiguanidesBiguanides

Biguanides

Glu

cose

(mg/

dL)

Bod

y W

eigh

t

Diabetesdiagnosis

50

100

150

200

250

300

350

Fasting glucose

Years

Rel

ativ

e A

mou

nt

-10 -5 0 5 10 15 20 25 30

Insulin resistance

Insulin level

Onset

High risk for diabetes

0

50

100

150

200

250

-15

Natural History of Type 2 Diabetes

Postmeal glucose

Incretin effectβ-cell function

Body weight

Kendall DM, et al. Am J Med. 2009;122(suppl 6):S37-S50. Simonson G, et al. Diabetes Manage. 2011;1:175-189.

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

Initial drug monotherapy

Efficacy ( HbA1c) Hypoglycemia Weight Side effects Costs

Healthy eating, weight control, increased physical activity

Metformin high low risk neutral/loss GI / lactic acidosis low

If needed to reach individualized HbA1c target after ~3 months, proceed to 2-drug combination (order not meant to denote any specific preference):

Metformin +

Metformin +

Metformin +

Metformin +

Metformin +

Efficacy ( HbA1c) Hypoglycemia Weight Major side effect(s) Costs

high low risk gain edema, HF, fx’s‡ high

Thiazolidine- dione

intermediate low risk neutral rare‡

high

DPP-4 Inhibitor

highest high risk gain hypoglycemia‡

variable

Insulin (usually basal)

Two drug combinations*

Sulfonylurea† +

Thiazolidine-dione +

DPP-4 Inhibitor +

GLP-1 receptor agonist +

Insulin (usually basal) +

Metformin +

Metformin +

Metformin +

Metformin +

Metformin +

TZD

DPP-4-i

GLP-1-RA

Insulin§

SU†

DPP-4-i

GLP-1-RA

Insulin§

SU† SU†

TZD TZD

TZD

DPP-4-i

Insulin§ Insulin§

If combination therapy that includes basal insulin has failed to achieve HbA1c target after 3-6 months, proceed to a more complex insulin strategy, usually in combination with 1-2 non-insulin agents:

Insulin#

Three drug combinations

More complex insulin strategies

or

or

or

or

or

or

or

or

or

or

or

or GLP-1-RA

high low risk loss GI‡ high

GLP-1 receptor agonist

Sulfonylurea†

high moderate risk gain hypoglycemia‡ low


T2DM Antihyperglycemic Therapy: General RecommendationsDiabetes Care, Diabetologia. 19 April 201[Epub ahead of print]

A1c Reduction of Oral Therapies Added onto Metformin (compared to placebo)

Phung O, Scholle J, Talwar M et al. JAMA 2010;303:1410‐1418

Comparison of Therapies Added onto Metformin (compared to placebo)

Phung O, Scholle J, Talwar M et al. JAMA 2010;303:1410‐1418

Hanefeld (n=500)

Charbonnel (n=630)

CHICAGO (n=462)

ADOPT (n=2897)

UKPDS (n=1573)

-2

-1

0

1

Cha

nge

in A

1C (%

)

Time (yrs)0 1 2 3 4 5 6 10

GlimepirideGlyburide

Glyburide

Glyburide

Gliclazide

Mazzone T. JAMA. 2006;296:2572-2581. Hanefeldd M. Cur Med Res Opin. 2006;22:1211-1215. Nissen SE. JAMA. 2008;299:1567-1573. UKPDS Study Group. Lancet.1998;352:837-853Charbonnel B. Diabetoogia. 2005;48(6):1093-1104.

Durability of Glycemic Control with Sulfonylurea Therapy

Glycemic control deteriorates with standard therapies

Cook MN et al. Diabetes Care. 2005;28:995‐1000.

N = 2220 with T2DM treated with SU + MET

≥109.0‐9.98.0‐8.94.0‐7.9

~85% of patients had A1C ≥8% after 4 years

Patients with

A1C ≥8%(%)

SU = sulfonylurea, MET = metformin

Pre‐SU A1C levels (%)100

80

60

40

20

00 1 2 3 4

Time from sulfonylurea initiation (years)

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

•Hypoglycemia

• Emerging concerns regarding association with increased mortality

• Associated with prolonged QT and arrhythmias

• Hypoglycemia due to Insulin and sulfonylureas represents at least 10% of ER visits for adverse drug reactions

• Proper drug selection in the hypoglycemia prone

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


When Goal is to Avoid Hypoglycemia

Concerns about Weight in Diabetes

• From 2007-2008 NHANES data, 32% of men and 36% of women are obese1

• Incidence of diabetes has doubled over the past 3 decades, primarily amongst obese individuals2

• In the NHANES data, the gains in life expectancy from smoking cessation are beginning to be outweighed by loss of life expectancy from obesity3

• Recent report: Increase of BMI by ≥ 1 kg/m2 after diagnosis: 63% increase CV death over 4.6 yrs4

1.

Flegal KM et al. JAMA 2010;303;235‐412.

Fox CS et al Circulation 2006;113:2914‐8

3.

Stewart ST et al. N Engl J Med 2009;361:2252‐604.

Bodegard J et al. Presented at EASD 2012





Metformin +

Metformin +

Metformin +

Metformin +

Metformin +



Thiazolidine- dione


high

DPP-4 Inhibitor


variable



Sulfonylurea† +


DPP-4 Inhibitor +



Metformin +

Metformin +

Metformin +

Metformin +

Metformin +

TZD

DPP-4-i

GLP-1-RA

Insulin§

SU†

DPP-4-i

GLP-1-RA

Insulin§

SU† SU†

TZD TZD

TZD

DPP-4-i

Insulin§ Insulin§

Insulin# (multiple daily doses)



or

or

or

or

or

or

or

or

or

or

or

or GLP-1-RA



Sulfonylurea†




When Goal is to Avoid Weight Gain





Metformin +

Metformin +

Metformin +

Metformin +

Metformin +



Thiazolidine- dione


high

DPP-4 Inhibitor


variable



Sulfonylurea† +


DPP-4 Inhibitor +



Metformin +

Metformin +

Metformin +

Metformin +

Metformin +

TZD

DPP-4-i

GLP-1-RA

Insulin§

SU†

DPP-4-i

GLP-1-RA

Insulin§

SU† SU†

TZD TZD

TZD

DPP-4-i

Insulin§ Insulin§

If combination therapy that includes basal insulin has failed to achieve HbA1c target after 3-6 months, proceed to a more complex insulin strategy, usually in combination with 1-2 non-insulin agents:

Insulin# (multiple daily doses)



or

or

or

or

or

or

or

or

or

or

or

or GLP-1-RA



Sulfonylurea†




When Goal is to Minimize Costs


Features to Include in a Cost AnalysisOral Agents GLP‐1RA Insulin

Drug Cost $ to $$$ $$$$ $ to $$$$

Hypoglycemia 0 to 0 to SMBG Need + + +++

Weight Gain None to some Loss Some

Training + ++ +++

Follow‐up + + +++

Reduction in other

Medications

Usually None Some None

Beta‐Cell Preservation

TZD’s=YesOthers=No/unk

nown

Unknown Maybe

Comparison of 3 Insulin Regimens: 4-T Study

Enrollment and Year 11 Receiving OAD or dual OAD (A1c 7%-10%), N=708

Biphasic BID, n=235

Prandial TID, n=239

Basal QD (or BID), n=234

If unacceptable A1c in Year 1, sulfonylurea replaced with second insulin type

Prandial at midday, n=159 (67.7%)2

+ +Basal at bedtime,

n=176 (73.6%)

+Prandial TID, n=191 (81.6%)

n=201 (86%) n=188 (79%) n=189 (81%)

Year 3: Completion

4-T, Treating to Target in Type 2 Diabetes; A1c, glycosylated hemoglobin; OAD, oral antidiabetic drug. 1.Holman RR et al. N Engl J Med. 2007;357(17):1716-1730. 2.Holman RR et al. N Engl J Med. 2009;361(18):1736-1747.

Patie

nts

With

A1c

≤6.

5%, %

4-T Study Outcomes: A1C Goal Achieved

Baseline A1C, 8.5%. 4-T, Treating to Target in Type 2 Diabetes; A1C, glycosylated hemoglobin.1. Holman RR et al. N Engl J Med. 2007;357(17):1716-1730. 2. Holman RR et al. N Engl J Med. 2009;361(18):1736-1747.

Biphasic Prandial Basal

17.0

31.9

23.9

44.8

8.1

43.2

0

10

20

30

40

50

Year 11 Year 32

P<.001

P=.001

P=.006

P=.03

4-T Study Outcomes: Insulin Doses

4-T, Treating to Target in Type 2 Diabetes.1. Holman RR et al. N Engl J Med. 2007;357(17):1716-1730. 2. Holman RR et al. N Engl J Med. 2009;361(18):1736-1747.

Year 11 Year 32

Insu

lin D

ose,

IU/d

0

20

40

60

80

100

BiphasicPrandialBasal

4-T Study Outcomes: Weight Change

4-T, Treating to Target in Type 2 Diabetes.1. Holman RR et al. N Engl J Med. 2007;357(17):1716-1730. 2. Holman RR et al. N Engl J Med. 2009;361(18):1736-1747.

Wei

ght C

hang

e Fr

om B

asel

ine,

kg

4.7

5.75.76.4

1.9

3.6

0

1

2

3

4

5

6

7

Year 11 Year 32

P<.001

P<.001

P<.001

P=.005P=.005

Biphasic Prandial Basal

Adding Exenatide BID to Optimized Glargine in T2DM Improves Glycemic Control Without Increasing Hypoglycemia

Incidence of hypoglycemia was similar in both groups; 1 patient in GLAR + PBO group had severe hypoglycemia

a P < .001 between-group difference.b P < .01 between-group difference.Results from 30-week RCT in 259 patients with T2DM. Buse J, et al. Ann Intern Med. 2011;154:103-112.

Parameter GLAR + EXN BID vs

GLAR + PBO

P

A1C, % −0.69 < .001

Weight, kg −2.74 < .001

b

aa

a

aa

234

216

198

180

144

126

Fasti

ng

Glucose Level (m

g/dL)

162

108

Mor

ning 2

‐h PP

G

Midd

ay pr

emea

l

Midd

ay 2‐

h PPG

Even

ing pr

emea

l

Even

ing 2‐

h PPG

0300

hour

s

GLAR + EXN BID, baselineGLAR + PBO, baselineGLAR + EXN BID, 30 wkGLAR + PBO, 30 wk

Liraglutide QD With Detemir QD Improves Glycemic Control in T2DM Over 38 Weeks

Incidence of hypoglycemia was similar in both groups; no major hypoglycemia occurred in either group

No major hypoglycemia occurred in any group during weeks 12to 38.Transient nausea occurred in 21% of patients during weeks 0 to 12, 4% of patients during weeks 12 to 38.

DeVries JH, et al. Diabetes Care. 2012 May 18. [Epub ahead of print];Rosenstock J, et al. Diabetes. 2011;60(suppl 1):A76 [abstr 276-OR].

Parameter LIRA + DET + MET vs LIRA + MET

P

A1C, % −0.52 < .0001

Weight, kg 0.79 .03

LIRA + DET + MET (n = 162)

LIRA + MET (n = 161)

234

198

180

162

108

90

Self‐Measured Plasma

Glucose (m

g/dL)

126

Befo

re di

nner

Bedt

ime

90 m

in af

ter

dinne

r

90 m

in af

ter

lunch

Befo

re lu

nch

90 m

in af

ter

brea

kfast

Befo

re br

eakfa

st

144

216

P = .0003

P = .0244

P = .0141

Decision Points for Choosing Drug Therapy

• Efficacy – BG and A1c lowering• Safety:

– Hypoglycemia risk– Side effects

• Effect on weight• CV risk factors:

– Outcome studies• Patient acceptance:

– Oral versus injected– Frequency of administration– Cost

• Desirable mechanism of action

Guidelines for Glycemic, Blood Pressure and Lipid Control

HDL = high-density lipoprotein; LDL = low-density lipoprotein; PG = plasma glucose; TG = triglycerides.

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

American Diabetes Association Goals

A1c < 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)

Clinical Guidelines for Treatment of Type 2 Diabetes

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Transcript of Clinical Guidelines for Treatment of Type 2 Diabetes