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New Perspectives in the
Management of
Type 2 Diabetes
Herold Merisier, MD, FAAFP
Voluntary Assistant Professor of Family Medicine
Miller School of Medicine, University of Miami
Plantation, FL
Disclosure
 Speaker: Novartis Pharmaceuticals
 Speaker: Novo-Nordisk
Diabetes 2010
 Epidemiology
 Diagnosis
 Screening
 Management of Type 2 Diabetes
 Patient Education
 Therapeutic Lifestyle Changes (TLC)
 Pharmacotherapy
 Treatment of co-morbid conditions
Diabetes in the US
 23.6 million children and adults affected (7.8% of the population)
 Diagnosed: 17.9 million people
 Undiagnosed: 5.7 million people
 1.6 million new cases in adults > 20y/o in 2007
 4300 new cases every day
 Pre-Diabetes: 57 million people
 2-4 fold increase in cardiovascular mortality and stroke
Center for Disease Control and Prevention
Available at: http://www.cdc.gov/diabetes/pubs/estimates07.htm#1
Diabetes in Canada
 1.8 million adults with Diabetes
 Prevalence: 4.8% (1998): 1 054 000 adult Canadians
 Prevalence: 5.5% (2005)
Available at: http://www.diabetes.ca/files/cpg2008/cpg-2008.pdf
Global Projections for the
Diabetes Epidemic: 2003-2025
NA
EUR
23.0 M
36.2 M
↑57.0%
48.4 M
58.6 M
↑21%
EMME
WP
19.2 M
39.4 M
↑105%
SEA
39.3 M
81.6 M
↑108%
AFR
SACA
World
2003 = 194 M
2025 = 333 M
↑ 72%
14.2 M
26.2 M
↑85%
7.1M
15.0 M
↑111%
2003
2025
M = million, AFR = Africa, NA = North America, EUR = Europe,
SACA = South and Central America, EMME = Eastern Mediterranean and Middle East,
SEA = South-East Asia, WP = Western Pacific
Diabetes Atlas Committee. Diabetes Atlas 2nd Edition: IDF 2003.
43.0 M
75.8 M
↑79%
Diagnosis
Normoglycemia
FPG < 100 mg/dl
2hPPG < 140 mg/dl
Impaired Glucose
Metabolism
FPG ≥ 100 mg/dl
< 126 mg/dl
IFG
2hPPG ≥ 140 mg/dl
< 200 mg/dl
IGT
Diabetes
FPG ≥ 126 mg/dl
(x 2)
2hPPG ≥ 200 mg/dl
or RPG ≥ 200 mg/dl w/
sx of Diabetes
HbA1c ≥ 6.5 (x 2)
IFG: Impaired Fasting Glucose
Glucose
IGT: Impaired Glucose Tolerance
FPG: Fasting Plasma Glucose RPG: Random Plasma
PPG: Post-Prandial Glucose
Adapted from Clinical Practice Recommendations. Diabetes Care, 2010
Screening
 All individuals ≥ 45y/o, particularly if BMI ≥ 25

if normal, repeat every 3 years
 Start screening at younger age if BMI ≥ 25 and:





physically inactive
first-degree relative with Diabetes
high risk ethnic group
h/o IFG, IGT, Gestational Diabetes, PCOS
Dyslipidemia or h/o cardio-vascular disease
 Fasting glucose or 2-hour OGTT
 Diabetes Risk Calculator
Diabetes Risk Calculator
 Gender
 Age
 Prior history of elevated blood glucose
 Height and weight
 Diet
 Smoking history
 Physical activity
 Family history
Diabetes Care. 2008 May;31(5):1040-5
Diabetes Risk Calculator
Available at: http://www.diabetes.org/diabetes-basics/prevention/diabetes-risk-test/
Diabetes Risk Calculator
Available at: http://www.diabetes.org/diabetes-basics/prevention/diabetes-risk-test/
QD Score (http://www.qdscore.org)
BMJ 2009;338:b880. Available at: http://bmj.com/cgi/content/full/338/mar17_2/b880
Management of Type 2 Diabetes
 Patient Education
 Therapeutic Lifestyle Changes (TLC)
 Pharmacotherapy
 Treatment of co-morbid conditions
Pharmacotherapy: Oral Agents
Class
Drugs
Mechanism of action
α-Glucosidase Inhibitor
Acarbose
Miglitol
Decrease carbohydrate absorption
in GI tract
Biguanides
Metformin
Decrease hepatic neoglucogenesis
Secretagogues
Sulfonylureas
Meglitinides
Glyburide, Glipizide,
Glimepiride
Repaglinide, Nateglinide
Stimulate β-cell to increase insulin
output
Thiazolidinediones
Pioglitazone (Actos®)
Rosiglitazone (Avandia®)
Improve insulin sensitivity,
decrease insulin resistance
DDP-4 Inhibitors
Sitagliptin (Januvia®)
Saxagliptin (Onglyza®)
Slow incretin metabolism, Increase
insulin synthesis/release, Decrease
glucagon levels
DPP-4 Inhibitors
Rosiglitazone (Avandia®)
 Contraindicated in patients with CHF
 Meta-analysis of 42 clinical studies:
 Mean duration 6 months; 14,237 total patients
 Rosiglitazone vs. placebo
 Increased risk of risk of myocardial ischemic events
 Three other studies
 Mean duration 41 months; 14,067 total patients
 Rosiglitazone vs. other oral diabetes medications or placebo
 Increased of MI neither confirmed nor excluded this risk
Progressive -cell Failure in Type 2 Diabetes
100
Diagnosis
80
60
40
20
0
-12
-6
0
6
12
Years
Based on data of UKPDS 16: conventional (diet) treatment group. Diabetes. 1995.
18
Pharmacotherapy:
Non-Insulin Injectables
Class
Drug
Mechanism of action
increases beta-cell
Exenatide (Byetta®)
response
GLP-1 Analog
decreases glucagon
(Incretin Mimetic)
Liraglutide (Victoza®) secretion
delays gastric emptying
slows gastric emptying
decreases glucagon
Amlynomimetic Pramlintide (Symlin®)
secretion
early satiety → weight loss
Pharmacotherapy: Insulin
(Older Agents)
Insulin Preparation
Onset
Peak
Duration
Short acting
Regular
30-60 min.
3-4h
6-8h
Intermediate
NPH
Lente
Ultralente
2-4h
3-4h
4-6h
6-10h
6-12h
10-16h
14-18h
16-20h
20-24h
30-60 min.
15-60 min.
Dual
Dual
14-18h
14-18h
Combinations
70% NPH / 30% reg
75% NPH / 25% reg
Pharmacotherapy: Insulin
(Newer Agents: Insulin Analogs)
Insulin Preparation
Rapid acting
Lispro (Novolog®)
Aspart (Humalog®)
Glulisine (Apidra®)
Long acting
Glargine (Lantus®)
Detemir (Levemir®)
Combinations
70% / 30% lispro
75% / 25% aspart
50% / 50% aspart
Onset
Peak
Duration
15-30 min.
15-30 min.
15-30 min.
30-90 min.
30-90 min.
30-90 min.
4-6h
4-6h
4-6h
1-2h
1-2h
flat
flat
24h
24h
30-60 min.
15-60 min.
15-60 min.
Dual
Dual
Dual
14-18h
14-18h
14-18h
Therapy for Type 2 Diabetes:
Sites of Action
Adipose
tissue
Pancreas
Sulfonylureas
Repaglinide
TZD
Glucose
Gut
 Glucose
uptake
Rosiglitazone
Pioglitazone
  -Glucosidase
inhibitors
Hyperglycemia
HGO*
Liver
Metformin
Thiazolidinediones
Acarbose
Miglitol
Muscle
Metformin
Thiazolidinediones
*HGO=hepatic glucose output.
Adapted from DeFronzo RA. Ann Intern Med. 1999;131:281-303.
Package Inserts for AVANDIA® (rosiglitazone maleate, GlaxoSmithKline), Actos® (pioglitazone HCl, Takeda),
Prandin® (repaglinide, Novo Nordisk), Precose® (acarbose tablets, Bayer), Glyset® (miglitol, mfd. by Bayer for
Pharmacia & Upjohn).
Stepwise Management of Type 2 Diabetes
+ +
+
Adapted from Williams G. Lancet 1994; 343: 95-100.
23
Pharmacotherapy
Stepwise Management

Glycemic targets often not met

Monotherapy often not effective long term

Therapy fails to address multiple impairments

Step-wise approach tends to perpetuate “failure”
New Treatment Paradigm
 Treatment designed to address multiple impairments
 Simultaneous rather than sequential therapy
 Combination therapy from the outset
 Early titrations to meet glycemic targets
Combination Oral Diabetic Agents
 Glucovance® ( Glyburide + Metformin)
 Metaglip® (Glipizide + Metformin)
 Avandamet® (Rosiglitazone + Metformin)
 Avandaryl® (Rosiglitazone + Glimepiride)
 ActoPlus Met® (Pioglitazone + Metformin)
 Janumet® (Januvia + Metformin)
ADA/EASD Consensus Algorithm 2009
Step 1
Step 2
Step 3
Tier 1: Well-validated core therapies
At Diagnosis
Lifestyle
+
Metformin
Lifestyle + Metformin
+
Basal Insulin
Lifestyle + Metformin
+
Sulfonylurea
Tier 2: Less well validated therapies
Lifestyle + Metformin
+
Pioglitazone
Lifestyle + Metformin
+
GLP1- Agonist
Lifestyle + Metformin
+
Intensive Insulin
Lifestyle + Metformin
+
Pioglitazone
+
Sulfonylurea
Lifestyle + Metformin
+
Basal Insulin
Nathan and Associates: Diabetes Care, Vol. 32, Number 1, January 2009
ACCE Diabetes Algorithm 2009
Glycemic Control Algorithm, Endocr Pract. 2009;15(No. 6)
Glucose Dynamics: Basal and Prandial
250
Postprandial hyperglycemia
200
Plasma
glucose
(mg/dL)
Type 2
diabetes
150
Basal hyperglycemia
100
50
Normal
0
0600
1200
1800
Time of day
Riddle MC. Am J Med. 2004;116(suppl):3S-9.
2400
0600
Basal-Bolus Combination Therapy
Breakfast
Bolus
insulin
Plasma
Insulin
Levels
Lunch
Bolus
insulin
Dinner
Bolus
insulin
Basal
insulin
4:00
8:00
12:00
16:00
Time
20:00
24:00
4:00
8:00
Treatment of co-morbid conditions

Dyslipidemia

Hypertension
Diabetes CV Risk Calculator
Available at: http://www.dtu.ox.ac.uk/riskengine/
Diabetes CV Risk Calculator
(Canada)
http://www.diabetes.ca/documents/about-diabetes/FINAL_PATIENT_TOOL_FOR_WEBSITE.pdf
The ABCs of Diabetes Care
 A1C
 ADA recommends < 7% in general, < 6% for selected
individuals
 AACE/IDF recommend ≤ 6.5%
 Blood pressure
 < 130/80 mm Hg
 Cholesterol




LDL-C: < 100 mg/dL (< 70 mg/dL in very high-risk patients)
HDL-C: > 40 mg/dL in men and > 50 mg/dL in women
Non-HDL-C: < 130 mg/dL (< 100 mg/dL in high-risk patients)
Triglycerides: < 150 mg/dL
American Diabetes Association. Diabetes Care. 2007;30(suppl 1):S4-S41.
American Association of Clinical Endocrinologists. Endocr Pract. 2007;13(suppl 1):3-68.
International Diabetes Federation. Diabet Med. 2006;23:579-593.
Additional Recommendations

Individualized Medical Nutrition Therapy

Exercise

Aspirin (75-325 mg/d)

Smoking cessation

Screening for microvascular complications (eyes,
kidneys, feet)

Immunization ( Flu vaccine, Pneumovax)

Recommended cancer screening
Optimal Care of the Diabetic Patient
Intensive
glycemic control
Aggressive Rx for
CV risk reduction
Lifestyle
interventions
• HbA1c <7%
• Dyslipidemia: Statin
• Proper nutrition
• Glucose (mg/dL):
Preprandial 90–130
Postprandial <180
• Hypertension: ≥2 drug
classes, include ACEI or ARB
• Physical activity
program
• Microalbuminuria:
ACEI or ARB
• Smoking cessation
• Use of aspirin
• CHD: ACEI, -blocker
• CVD/high risk: ACEI
ADA. Diabetes Care. 2005;28(suppl 1):S1-79.
• Weight control
Thank You For Your
Attention
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