Diabetes Update 2013
Dr. Erin Koepf, PharmD, BCACP
Assistant Professor, Ambulatory Care
University of New England College of Pharmacy
Maine Pharmacists Association, September 7, 2013
1
Objectives:
• Based on the American Diabetes Association Standards of Medical
Care in Diabetes – 2013:
• Identify the classification, risk factors, diagnosis, and screening
criteria for diabetes
• Explain pharmacologic and non-pharmacologic treatments options
for patients with diabetes or pre-diabetes
• Describe measures that can be taken to prevent diabetes
progression and complications including immunization
recommendations
2
Objectives:
•
Identify the class, mechanism of action, dosing, and administration of new
and common diabetes medications
•
Discuss with patients and other health care practitioners diabetes treatment
options, monitoring, and the goals for therapy
•
Compare and contrast medication therapies available for the treatment of
diabetes and select appropriate options for a given patient
•
Develop a comprehensive care plan for a given patient with diabetes which
included pharmacologic and non-pharmacologic measures, monitoring, and
preventative measures
3
“What is Diabetes?” Warm-up
• Spend 60 seconds thinking about and writing down a
description of Diabetes
• Spend the next 2 minutes sharing your description with
someone next to you
• Write down some of the concepts you come up with
4
“What is Diabetes?” Warm-up
• Endocrine condition that increases risks of Cardiovascular
events v.
• Cardiovascular disease with abnormal processing and
distribution of glucose
• Others?
5
Review: Diabetes Pathogenesis
• Insulin deficiency
• Quantitative: decreased in production by the β-cells of the pancreas
• Qualitative: insulin resistance especially muscle, liver, adipose,
myocardial
• Improvements in insulin function
• Weight loss to decrease insulin resistance
• Can in turn improve β-cell function
6
Review: Diabetes Pathogenesis
•
Excess secretion of glucagon by α-cells of pancreas
•
Glucose overproduction by liver; underutilized by body
•
Gluconeogenesis (making glucose from glycerol and amino acids)
•
Renal tubular transport of glucose to the urine due to hyperglycemia
•
Incretin system deviations (relationship to DM still not fully clear)
•
Glucagon-like peptide 1 (GLP-1)
•
Glucose dependent insulinotropic peptide (GIP)
7
Who has Diabetes?
• Incidence of diabetes is rising (about 25 million adults in the US)
• Incidence is higher in certain populations
• Many risk factors/associated conditions are also rising in prevalence
• About 2/3 of patients with diabetes in the US also have hypertension
(HTN)
• How does Maine compare to the US when it comes to incidence of
Diabetes?
8
Incidence of Diabetes in the US
9
Centers For Disease Control and Prevention. Diabetes Data and Trends.
.http://apps.nccd.cdc.gov/DDT_STRS2/NationalDiabetesPrevalenceEstimates.aspx?mode=DBT
Diabetes Report Card 2012. Atlanta, GA: Centers for Disease Control
and Prevention, US Department of Health and Human Services; 2012.
Diabetes in the US
•
Incidence increases with
age
•
Incidence ranges from
7.1% - 16.1% between
different racial/ethnic
groups
10
Diabetes Report Card 2012. Atlanta, GA: Centers for Disease Control
and Prevention, US Department of Health and Human Services; 2012.
New Cases of Diabetes
11
Diabetes Report Card 2012. Atlanta, GA: Centers for Disease Control
and Prevention, US Department of Health and Human Services; 2012.
Rates of Diabetes
in Maine have
been similar to that
of the US
12
Diabetes Surveillance Report, Maine 2012. Augusta, ME: Diabetes Prevention
and Control Program, Maine Center for Disease Control and Prevention; 2012.
Diabetes Incidence in Maine
13
Diabetes Surveillance Report, Maine 2012. Augusta, ME: Diabetes Prevention
and Control Program, Maine Center for Disease Control and Prevention; 2012.
Prevalence Varies
throughout Maine
from 7% to 10.7%
14
Diabetes Surveillance Report, Maine 2012. Augusta, ME:
Diabetes Prevention and Control Program, Maine Center for
Disease Control and Prevention; 2012.
Diabetes Disease Burden
•
•
2009 in Maine, diabetes related deaths had incidence of 65.8 per 100,000
•
Decreased from 81.5 per 100,000
•
US 2008 incidence was 72.2 per 100,000
Significantly increased risk of cardiovascular diseases
•
•
Leading cause of
•
•
Including stroke and myocardial infarction (MI)
Non-traumatic lower extremity amputations, blindness, and kidney failure
Medical expenditures are on average 2.3 times higher in patients with diabetes than
those without (~ $ 174 billion in direct + indirect costs in 2007)
Diabetes Surveillance Report, Maine 2012. Augusta, ME: Diabetes Prevention
and Control Program, Maine Center for Disease Control and Prevention; 2012.
15
Diabetes Report Card 2012. Atlanta, GA: Centers for Disease Control
and Prevention, US Department of Health and Human Services; 2012.
Microvascular Complications:
• Nephropathy
• Retinopathy
• Neuropathy
• Foot ulcers/lesions
• Numbness, pain
• Sexual dysfunction
• Gastroparesis
16
http://www.mayomedicallaboratories.com/images/articles/communique/2009/09fig1.jpg
Macrovascular Complications
• Cardiovascular Diseases (CVD)
• Coronary Artery Disease (CAD)
• Myocardial Infarction (MI)
• Stroke or transient ischemic
attack (TIA)
• Peripheral Artery Disease (PAD)
17
http://womenshealth.gov/heart-health-stroke/images/heart-attack-signs.gif
Additional Concerns
• Depression and other mental
disorders
• Dental disease
• Increased risk of infection
• Can affect fertility
• Severe hyper- or hypoglycemic events
http://diabeticradio.com/wp-content/uploads/2010/06/hypoglycemia.jpg
18
Diabetes Preventative Care
19
Diabetes Report Card 2012. Atlanta, GA: Centers for Disease Control
and Prevention, US Department of Health and Human Services; 2012.
Preventative Care in Maine
Diabetes Surveillance Report, Maine 2012. Augusta, ME: Diabetes Prevention
and Control Program, Maine Center for Disease Control and Prevention; 2012.
20
How do we classify and
diagnose diabetes?
• Types
• Diagnosis
• Screening
• Case
http://a.abcnews.com//images/Health/diabetes_Screening3_mn.jpg
21
Diabetes Classification
• Type 1 Diabetes
• Type 2 Diabetes
• Gestational Diabetes (GDM)
• Other types related to other causes
• Exocrine diseases (i.e. cystic fibrosis)
• Genetic defects affecting insulin action or production
• Drug/chemically induced (i.e. HIV/AIDs treatments)
22
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Diagnosis of Diabetes:
Measurements that may be used
•
Fasting Plasma Glucose (FPG)
•
•
Blood glucose measured after 8 hours fasting
Oral Glucose Tolerance test (OGTT)
•
Blood glucose measured 2 hours after 75 gram glucose load (use of anhydrous
glucose solution)
•
Glycosylated hemoglobin or Hemoglobin A1c (A1C)
•
•
Test without regard to meals, provides 3 month mean glucose
Random plasma glucose (PG)
•
For use in patients with symptoms of hyperglycemia/hyperglycemic crisis
23
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Diagnosis of Diabetes:
Symptoms/Presentation
•
•
Assessment for signs and symptoms of hyperglycemia
•
Excess thirst, urination, and/or hunger
•
Blurry vision or vision changes
In severe hyperglycemia (BG > 240 mg/dL)
•
Ketones may be present in urine
•
Ketoacidosis can occur when the body breaks down fat and other molecules
for energy
•
Can not use glucose for energy without insulin
24
Diagnosis of Diabetes:
Values for Diabetes/Pre-Diabetes
Measurement
Criteria for
Diabetes
Criteria for PreDiabetes
FPG
≥ 126 mg/dL
100 - 125 mg/dL
OGTT
≥ 200 mg/dL
140 - 199 mg/dL
A1C
≥ 6.5%
5.7 - 6.4%
Random PG
≥ 200 mg/dL
N/A
25
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Pre-Diabetes Diagnosis
• Plasma glucose and/or A1C level between normal range and
diabetes
• Risk for developing DM and CVD
• Estimates for developing diabetes over 5 years range from
9 - 50 %
• Evaluate and treat other risk factors:
• Obesity/overweight, dyslipidemia, and hypertension
26
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Who to Test/Screen for Diabetes?
• For which patients should you be recommending
testing/screening for Diabetes?
• When/How often should they be screened?
• Evaluate individual patient risk
• Assess previous screening results
• What risk factors can you name?
27
Risk Factors*
•
•
•
•
•
Obesity/overweight (BMI ≥ 25 kg/m2)
History of CVD
Physical inactivity
Prior diagnosis of pre-diabetes
First degree relative with DM
HDL cholesterol < 35 mg/dL
Triglycerides > 250 mg/dL
High risk ethnicity/race:
African American
Latino
Native American
Asian Amerian
Pacific Islander
Women with history of GDM or delivering a
baby weighing > 9 lbs
Women with Polycystic Ovarian Syndrome
(PCOS)
Hypertension: BP ≥ 140/90 mmHg
or on treatment
•
•
28
Conditions associated with insulin
resistance:
Severe obesity (BMI ≥ 40 kg/m2)
Acanthosis Nigrans
Who to Screen for Diabetes?
• All adults ( ≥ 18 years old) with BMI ≥ 25 kg/m2 and 1 or more
additional risk factors*
• In adults without additional risk factors
• Screening should start at age 45
• If results of screening are normal; repeat in 3 years
• Repeat yearly in those with Pre-diabetes values
• For diagnosis screening test must be repeated
• Is better to use same test (i.e. A1C, FPG, etc) for repeat
29
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Screening in Children and Adolescents
•
Test for type 2 diabetes and pre-diabetes in children/adolescents
•
Overweight (BMI > 85th percentile for age and gender or > 120% of
ideal weight for height)
•
Plus 2 risk factors:
•
Family history in 1st or 2nd degree relative
•
Race/ethnicity (same as in adults)
•
Signs of insulin resistance or associated conditions
•
Gestational DM in mother while child was in utero
30
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Screening for Gestational Diabetes
•
Screen at first pre-natal visit for those with risk factors
•
Without risk factors screen at 24-28 weeks
•
•
Use OGTT for diagnosis (fasting, 1 hour, and 2 hour)
•
FPG ≥ 92 mg/dL
•
1 hour ≥ 180 mg/dL
•
2 hour ≥ 153 mg/dL
In women with gestational DM, screen for type 2 DM at 6-12 weeks postdelivery then every 3 years
31
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Who to screen for Diabetes?
•
1.
Which of the following symptom-free patients is due to be screened for diabetes
today?
•A.
50 year old Latina female who delivered a baby weighing 10 lbs when she was
27, but had a negative diabetes screening test 24 months ago
•B.
25 year old Caucasian female with a BMI of 28 kg/m2 who reports low to no
physical activity and is taking medication to treat his hypertension
•C. 40 year old African American male with a BMI of 24 kg/m2 and family history
significant for diabetes in his mother and maternal grandfather
•D.
42 year old Caucasian male with a BMI of 26 kg/m2 who has no comorbidities
and is physically active, but has never been screened
32
Meet Mr. L. Labor
33
Patient: L. Labor
•
25 year old Caucasian Male who frequents your community pharmacy and has just
been to his doctor’s office (routine visit)
•
Claims he is generally “healthy” (admits his diet could be better)
•
BMI = 28 kg/m2 (height: 73 inches; weight: 215 lbs)
•
Has a wife and daughter (~ 1 year old)
•
Previously had a very physically active job, but now spends most of his time
sitting at a computer both at work and at home
•
Carpentry and Coaching little league v.
•
Webpage design and Watching games from the stands with snacks
34
Patient: L. Labor
• He mentions his doctor wants him to get lab work done to check for
diabetes
• He does not understand why
• He feels he is young and healthy
• How can you explain to him the importance and potential benefit to
having the tests done?
• Can you explain to him what diabetes is and what it means for his
health?
35
Interpreting test results
• Which of the following values is one of the criteria for the
diagnosis of pre-diabetes?
•A. Glycosylated Hemoglogbin (A1C) = 6.2 %
•B. Fasting Plasma Glucose (FPG) = 90 mg/dL
•C. Plasma Glucose 2 hours after a 75 grams glucose
load = 130 mg/dL
•D. Glycosylated Hemoglogbin (A1C) = 5.7 %
36
Diagnosis of Diabetes:
Values for Diabetes/Pre-Diabetes
Measurement
Criteria for
Diabetes
Criteria for PreDiabetes
FPG
≥ 126 mg/dL
100 - 125 mg/dL
OGTT
≥ 200 mg/dL
140 - 199 mg/dL
A1C
≥ 6.5%
5.7 - 6.4%
Random PG
≥ 200 mg/dL
N/A
37
Interpreting test results
• What does it mean if LL’s lab test shows:
•Glycosylated Hemoglogbin (A1C) = 6.0 %
•And
•Fasting Plasma Glucose (FPG) = 110 mg/dL
• What else would you like to know about him or test for?
• What should we recommend for him going forward?
38
Next Steps
•To prevent/delay the onset of Type 2 Diabetes in patients who have been
diagnosed with Pre-diabetes, which of the following are recommended as part of
an ongoing support plan:
•A. Weight loss of 7% of the patient’s initial body weight
•B. Moderate physical activity for a minimum of 150 minutes/week
•C. Initiation of canagliflozin therapy
•D. A and B are correct
•E. A, B, and C are all correct
39
Treatment for Pre-Diabetes
40
http://www.diabetes-warrior.net/wp-content/uploads/2010/10/pre-diabetes1.jpg
Lifestyle Modifications for
Pre-Diabetes and Diabetes
•
Medical Nutrition Therapy (MNT)
•
•
Increased physical activity
•
•
Minimum 150 minutes/week moderate level
Weight loss/maintenance
•
•
Moderation, variety of carbohydrates
Initial 7% of body weight and maintenance of weight loss
Smoking cessation
•
Encourage and support with counseling and/or pharmacotherapy
41
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Lifestyle Modifications for
Pre-Diabetes and Diabetes
•
Can decrease progression from pre-DM to DM
•
Group and individual delivery methods have both been found to be
effective
•
Monitoring for and managing other CVD risk factors:
•
Hypertension (HTN)
•
Hyperlipidemia (HLD)
•
Overweight/obesity (especially excessive abdominal fat)
•
Tobacco use
42
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Lifestyle Modifications for
Pre-Diabetes and Diabetes
• What specifically could you recommend for LL?
• Work with 1 -2 others for 2-3 minutes writing
down specific recommendations for LL
43
Specific Recommendations for LL:
•
Smoking cessation (assessment of readiness to quit)
•
Healthful diet and exercise plan with goal of 15 lbs weight loss
•
Limit intake of high sugar beverages
•
Increase intake of whole grains to obtain recommended intake of fiber
•
Recheck BP, recommend treatment if it continues to be elevated
•
Check fasting lipid panel, recommend treatment if levels are elevated
•
Annual monitoring for development of DM
•
Medication therapy for Pre-Diabetes?
44
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Pharmacotherapy for
Pre-Diabetes
•Which of the following answers lists medications that can help prevent/delay the
progress from pre-diabetes to diabetes?
•A. Pioglitazone and Glipizide
•B. Orlistat and Sitagliptin
•C. Acarbose and Pioglitazone
•D. Any of the above
45
Metformin for Pre-Diabetes
• Can be considered for all patients with Pre-diabetes as adjunct to
lifestyle modification
• Especially recommend for patients with
• Elevated FPG ( > 100 mg/dL)
• BMI > 35 kg/m2
• Aged < 60 years old
• History of GDM (women)
46
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Progress….
• LL follows recommendations from you and his other health care
providers
• He is able to quit smoking with nicotine patches and counseling,
but during this time his weight goes up 2.5 kg
• About 6 months later he begins a diet and exercise program for
patients with Pre-Diabetes
• He is able to loose ~ 20 lbs but has been struggling to keep
from gaining it back
47
Progress….
• LL has tolerated Metformin therapy and is now taking 1
gram BID
• He is exercising more, but he is still having difficulties
balancing his diet
• He was diagnosed with high blood pressure
• Not currently on therapy - improved with smoking
cessation and weight loss
48
8 years later….
• He comes into the pharmacy today for his Metformin refill and
reports bad news…
• Despite his lifestyle changes he has been diagnosed with
type 2 diabetes
• His A1c has reached 8.1% and he has had two FPGs > 140
mg/dL drawn by the lab over 2 weeks
• He is motivated to continue with his lifestyle changes, but
wants to know more about additional medications
49
Adding on more medications
• Individually take 1 minute to list additional diabetes therapies
that could be added to LL’s Metformin for better glycemic
control
• In pairs take a few minutes to discuss your options
• Select and write down one agent/class that you would
recommend for him based on his current status
• Write down why you think it is a good choice for him
50
Adding on Therapy
•
While metformin is still the preferred first line therapy for patients with diabetes, if maximum
doses of metformin do result in an A1C at goal, how should an additional agent be chosen?
•A. The second agent added on should be a Glucagon-Like-Peptide-1 (GLP-1) receptor agonist
•B. The second agent added on should be selected based on patient specific factors with
consideration of cost, potential side-effects, and comorbidities
•C. The second agent should be insulin therapy with insulin glargine daily and insulin aspart or
lispro TID with meals
•D. A second agent should not be added until diet and lifestyle goals have been achieved to
reduce insulin resistance
51
A Patient Centered Approach
• American Diabetes Association (ADA) and the European
Association for the Study of Diabetes (EASD) 2012
recommendations
• Patient be involvement in decision making
• Patient factors be considered in selecting treatments and goals
of therapy
• Most add-on therapy will offer similar glycemic benefit, but
compliance and risk of adverse events varies
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes:
a patient52
centered approach, Position Statement by the ADA and the EASD. Diabetes Care. 2012;35:1364-79.
Factors to Consider
•
Think of each element as a continuous spectrum:
•
Patient attitude and expected treatment efforts
•
Risks of hypoglycemia and other adverse events
•
Disease duration
•
Life expectancy
•
Important comorbidities
•
Established vascular complications
•
Resources, support system available
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes:
a patient53
centered approach, Position Statement by the ADA and the EASD. Diabetes Care. 2012;35:1364-79.
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes:
a patient54
centered approach, Position Statement by the ADA and the EASD. Diabetes Care. 2012;35:1364-79.
Factors to Consider
•
•
Factors should also be considered in prescribing lifestyle modifications
•
Setting goals that are realistic
•
Adapting to patient situations
These may include:
•
Access to healthful foods
•
Access to a safe environment for exercise
•
Patient’s physical ability (i.e. Fall risk, respiratory conditions)
55
Adding on Therapy
•
While metformin is still the preferred first line therapy for patients with diabetes, if
maximum doses of metformin do result in an A1C at goal, how should an additional
agent be chosen?
•B. The second agent should be insulin therapy with insulin glargine daily and insulin
aspart or lispro TID with meals
•
This strategy of starting insulin as first line (with or without metformin) may be
appropriate for patients with severe hyperglycemia at time of diagnosis or therapy
initiation
•A1C ≥ 10% or Blood glucose > 300 mg/dL
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes:
a patient56
centered approach, Position Statement by the ADA and the EASD. Diabetes Care. 2012;35:1364-79.
Adding on Therapy
• While metformin is still the preferred first line therapy for patients with
diabetes, if maximum doses of metformin do result in an A1C at goal,
how should an additional agent be chosen?
•A. The second agent added on should be a Glucagon-Like-Peptide-1
(GLP-1) receptor agonist
• This may be appropriate for patients in whom weight gain is desirable,
patient has insurance that will cover cost (reasonable copay), and
patient feels comfortable with injectable therapy
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes:
a patient57
centered approach, Position Statement by the ADA and the EASD. Diabetes Care. 2012;35:1364-79.
Oral Medication Options
•
Biguanides (metformin)
•
Sulfonylureas
•
Dipeptidyl peptidase IV
•
•
•
(DPP-IV)
inhibitor
•
•
Sitagliptin
•
Saxagliptin
•
Linagliptin
•
Alogliptin
Thiazolidinediones (TZDs)
α-Glucosidase inhibitors
•
•
58
Colesevelam
Dopamine-2 agonists
•
Meglitinides
Acarbose, Miglitol,
Bile acid sequesterants
•
•
Only Pioglitazone
Bromocriptine
New Oral Options
• Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors
• Dapagliflozin (Forxgia)
• 2011, FDA declined approval (concerns over risk of breast and
bladder cancer)
• July 2012 NDA resubmitted to FDA with new data
• Has been approved in the EU, Australia, New Zealand, Mexico, and
Brazil
• Canagliflozin (Invokana) - approved earlier this year
59
New Oral Options
• Sodium-Glucose cotransporter 2 (SGLT2) inhibitors
• Lowers blood glucose by decreasing the amount of glucose
re-absorbed by the kidneys
• Canagliflozin (Invokana®)
• Moderate A1C reduction and weight reduction
• Low incidence of hypoglycemia
• Renal monitoring and dose adjustment
60
Invokana (package insert). Janssen Pharmaceuticals, Inc. Titusville, NJ. March 2013; http://www.invokanahcp.com/. Accessed: 08/28/13.
Canagliflozin (Invokana®)
•
Approved for treatment of adults with type 2 Diabetes in conjunction with lifestyle
interventions
•
Initiate at 100 mg PO daily, before first meal of the day
•
Can increase to 300 mg PO daily if eGFR ≥ 60 mL/min (if less max dose = 100
mg/day)
•
Contraindicated with hypersensitivity, ESRD, dialysis
•
•
Avoid or discontinue if eGFR < 45 mL/min
Additional Warnings include:
•
Hypotension, hyperkalemia, hypoglycemia, mycotic genital infections, and
increased LDL cholesterol
61
Invokana (package insert). Janssen Pharmaceuticals, Inc. Titusville, NJ. March 2013; http://www.invokanahcp.com/. Accessed: 08/28/13.
Canagliflozin (Invokana®)
•
•
•
•
•
Significant Interactions
Common Adverse Events ( ≥ 5%)
Rifampin (UGT inducers)
•
Urinary track infections (UTIs)
•
•
Mycotic genital infections
•
Increased frequency and/or volume of
~50% decrease in AUC
Increased digoxin Cmax and AUC
urination and nocturia
Pharmacokinetics
•
•
~ 65% absorption
Less common include:
•
Hypersensitivity reaction
•
Constipation
to inactive metabolites
•
Thirst
•
~33% excreted in urine
•
Nausea and abdominal pain
•
~ 40 excreted unchanged in feces
•
~99% protein bound in plasma
•
O-glucuronidation via UGT1A9 and UGT2B4
62
Invokana (package insert). Janssen Pharmaceuticals, Inc. Titusville, NJ. March 2013; http://www.invokanahcp.com/. Accessed: 08/28/13.
Injectable Medication Options
•
•
Insulins
•
Long acting, short acting, rapid acting, and premixes
•
Insulin Degludec - FDA declined approval; requesting more data
Glucagon-like peptide - 1 receptor agonists
•
Exenatide, liraglutide
•
Albiglutide - may be next agent in class (FDA petition submitted by GlaxoSmithKline
Jan 2013); proposed for once weekly injection
•
Amylin mimetics
•
Pramlintide - use with insulin; mostly in patients with type 1 DM
63
Ultra-long Acting Insulin?
• Insulin Degludec
• Proposed to have > 24 hour activity to give better once daily dose
coverage than other products
• Half-life ~ 42 hours
• FDA declined to approve as of Feb 2013
• Requested more long term cardiovascular safety data from
dedicated trial
• Has been approved in the European Union
64
Tucker ME. FDA rejects Novo Nordisk’s Insulin Degludec. Medscape News. Available at: http://www.medscape.com/viewarticle/779077
Injectable Agent Dosing
•
Which of the following answers correctly lists medication name, strength, and
starting dose for a Glucagon-Like Peptide-1 (GLP-1) receptor agonist?
•A. Liraglutide (Victoza®) 0.6 mg injected SubQ once daily without regard to
meals
•B. Exenatide (Byetta®) 5 mg injected SubQ BID 60 minutes or less before a
meal
•C. Exenatide (Bydureon®) 2 mg injected SubQ once weekly, must be with a
meal
•D. Both A and C are correct
•E. A, B, and C are all correct
65
Back to adding on therapy
• Any changes in what you would like to recommend for LL?
• Comparative analysis of add-on therapy has indicated that most 2
drug combinations have similar A1C lowering effects
• Variance is greater in incidence of hypoglycemia and other
side-effects
• For each patient must consider risk v. benefit of each medications
positive and negative effects
Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications
for type 2
66
diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med. 2011;154:602-13.
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes:
a patient67
centered approach, Position Statement by the ADA and the EASD. Diabetes Care. 2012;35:1364-79.
Goals for therapy
•
Choosing an A1C goal for a patient should be individualized just like the
therapy selected
•
Guidelines recommend lowering A1C to below or around 7% to reduce
microvascular complications (range 6.5% - 8%)
•
May also reduce macrovascular complications in some patients if
implemented soon after diagnosis
•
For other patients, older, greater duration of disease, benefit of lower A1C
may not outweigh risk of hypoglycemia
•
Variance in cardiovascular outcomes between large trials
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes:
a patient68
centered approach, Position Statement by the ADA and the EASD. Diabetes Care. 2012;35:1364-79.
Brief on Trials for Tight Glycemic Control
•
UKPDS
•
•
Intensive Control associated with improved microvascular outcomes
ACCORD
•
Intensive therapy/targets increased mortality without significantly reducing cardiovascular
events
•
ADVANCE
•
Intensive control resulted in relative reduction of combined major cardiovascular events and
microvascular events
•
VADT
•
No significant effect on rates of major cardiovascular events, death, or microvascular
complications
The Action in Diabetes and Vascular Disease: Preterax and Diamicron
Modified Release Controlled Evaluation (ADVANCE) Collaborative
Group. NEJM. 2008;358(24):2560-72.
69
Duckworth W, Abraira C, Moritz T, et al. NEJM. 2009;360(2):129-39.
Stratton IM, Adler AI, Neil HAW, et al. BMJ. 2000;321:405-12.
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group. NEJM. 2008;358(24):2545-59.
Meta-analysis on tight glycemic control
•
•
Lancet 2009: based on 5 randomised trials
•
Intensive therapy reduces coronary events without an increased risk of death
•
Notes variance between populations and rate of A1C reduction
BMJ 2011: based on 14 randomised trials (used trial sequence analysis)
•
Intensive control has not been proven to reduce all cause mortality
•
Increase in relative risk of hypoglycemia by 30 %
•
Evidence insufficient to draw conclusions on cardiovascular mortality, non-
fatal MI, composite microvascular complications, or retinopathy
Ray KK, Kondapally Seshasai S, Wijesuriya S, et al. Lancet. 2009;373:1765-72.
70
Hemmingsen B, Lund SS, Gluud C, et al. BMJ. 2011;343:d6898 Doi: 10.1136/bmj.d6898.
Meta-analysis on tight glycemic control
•
BMJ 2011: based on 13 studies
•
Limited benefits to all cause mortality and cardiovascular-related death
•
Values on both sides of the debate can not be ruled out by this analysis
•
Risk and benefit for microvascular and macrovascular complications -
inconclusive
•
•
Risk of harm with hypoglycemia noted
Need for more trials
71
Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. BMJ. 2011;343:d4169 doi:10.1136/bmj.d4169.
What should be goal for LL?
• What do you think we should set at LL’s A1C goal?
• How about other goals/plans?
• Self-monitoring of blood glucose (SMBG)
• Preventative Care
• Cardiovascular risk reduction
• Medical Nutrition Therapy (MNT)
72
Potential Plans for LL
• A1C ≤ 7% (depending on response to therapy)
• Check A1C at least twice per year
• Check more often when changing therapies or above goal
• Diabetes Self-Management Education (DSME) and support
• Initial education plus follow-up
• Education should address quality of life and psychosocial issues
• May be recommended for patients with Pre-Diabetes as well
73
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Potential Plans for LL
•
SMBG
•
Part of comprehensive DM education and care discussion with patient
•
Daily monitoring is not required for most patients not taking insulin
•
Consider patient comfort, access to testing supplies, and risk of
hypoglycemia based on medication therapy
•
Goals and frequency should be individualized; can consider:
•
Fasting BG range 70 - 130 mg/dL
•
Peak Post-prandial BG < 180 mg/dL (taken 1-2 hours after meal)
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American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Medical Nutrition Therapy
•
Weight loss (overweight/obese) and weight maintenance
•
Use of low carbohydrate, low fat calorie-restricted, or Mediterranean diet
•
Monitor lipids, renal function, and protein intake
•
Individual diet plan for intake of carbohydrates, proteins, and fats
•
Saturated fat < 7 % of total calories (9 calories per gram of fat); limit trans fats
•
Addition of physical activity (design to meet patient’s ability)
•
Increase intake of whole grains to get recommended daily intake for fiber
•
Limit alcohol intake to moderate (1 drink per day women; 2 per day men)
•
Specific vitamin supplementation not currently supported by evidence
75
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Cardiovascular Prevention
•
Hypertension
•
New goal option of systolic < 140 mmHg; Diastolic < 80 mmHg
•
Lower targets (< 130 mmHg) may be appropriate for specific patients
(younger)
•
Preferred treatment
•
DASH Diet and lifestyle modification
•
Angiotensin Converting Enzyme (ACE) Inhibitors or Angiotensin Receptor
Blocker (ARB) (monitor renal function and electrolytes)
•
Addition of diurectics or other agents may be required to reach goal
76
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Cardiovascular Prevention
•
Hyperlipidemia
•
Monitor fasting lipids annually
•
Or every 2 years if at goal and stable
•
Lifestyle modifications recommended for all patients
•
Recommend addition of HMG-CoA Reductase Inhibitor (statin) therapy
regardless of baseline lipid values if patient has CVD or
•
Over the age of 40 with 1 or more CVD risk factors
•
Family history of CVD, HTN, smoking, albuminuria, dyslipidemia
77
Cardiovascular Prevention
•
Hyperlipidemia
•
•
For lower risk individuals add statin if
•
Lifestyle changes alone do not reduce LDL to < 100 mg/dL
•
Patient has multiple CVD risk factors
If patients do not meet goals (see next slide) on maximum tolerated statin
dosing
•
•
Alternative goal: LDL reduction by 30 - 40 % from baseline
Combination therapy has not been shown to have additional
cardiovascular benefit
78
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Cardiovascular Prevention
• Hyperlipidemia
• LDL Goals (primary target of therapy)
• < 100 mg/dL for patients without CVD
• < 70 mg/dL for patients with CVD
• Triglyceride goal < 150 mg/dL
• HDL goal for men > 40 mg/dL
• HDL goal for women > 50 mg/dL
79
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Cardiovascular Prevention
•
Anti-platelet agents
•
Can use aspirin 81 mg daily as primary prevention in patients with type 1
or type 2 DM at increased risk( 10 year risk > 10%)
•
•
Includes most men > 50, women > 60 with at least 1 risk factor
For patients with lower risk (10 risk < 5%) with no risk factors - therapy is
not recommended
•
For patients at moderate risk, must weigh risks and benefits
•
For secondary prevention, aspirin 81 mg is recommended
•
May use clopidogrel with documented aspirin allergy
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American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
General Prevention
•
Monitoring of renal function
•
Treatment of elevated urinary albumin excretion with ACE Inhibitors or
ARBs
•
Eye exams yearly
•
Foot care and exams
•
Skin care
•
Vaccinations
•
Social support
81
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66.
Prevention: Immunizations
• You are working with a 30 year old gentleman who has just been
diagnosed with type 2 Diabetes. Which vaccines would you recommend
he receive if he has not done had them already?
•A. Hepatitis B series
•B. Influenza (to be repeated annually)
•C. Pneumoccal Polysaccharide
•D. Both B and C are correct
•E. A, B, and C are all correct
82
Useful Abbreviations:
ADA
American Diabetes Association
A1c or A1c
Hemoglobin A1c
FPG
Fasting Plasma Glucose
OGTT
Oral Glucose Tolerance Test
BG
Blood Glucose
IFG
Impaired Fasting Glucose
IGT
Impaired Glucose Tolerance
DM
Diabetes Mellitus
HTN
Hypertension
HLD
Hyperlipidemia
MI
Myocardial Infarction
CAD
Coronary Artery Disease
CVD
Cardiovascular Disease
PAD
Peripheral Artery Disease
TIA
Transient Ischemic Attack
83
References:
•
American Diabetes Association (ADA) Professional Practice Committee. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1):
S11-S66.
•
Centers for Disease Control and Prevention. Diabetes Report Card 2012. Atlanta, GA: Centers for Disease Control and Prevention, US Department
of Health and Human Services; 2012. Available at: www.cdc.gov/diabetes/pubs/pdf/DiabetesReportCard.pdf
•
Centers for Disease Control and Prevention. National Diabetes Fact Sheet, 2011. Atlanta, GA: Centers for Disease Control and Prevention, US
Department of Health and Human Services; 2011. Available at: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf.
•
Diabetes Surveillance Report, Maine 2012. Augusta, ME: Diabetes Prevention and Control Program, Maine Center for Disease Control and
Prevention; 2012. Available at: http://www.maine.gov/dhhs/mecdc/population‐health/dcp/statistics.htm
•
Maine Center for Disease Control and Prevention. Maine Diabetes Prevention and Control Program, Health Fact Sheet: Diabetes in Maine. Maine
Center for Disease Control and Prevention, Maine Department of Health and Human Services; 2011.
•
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach, Position Statement by
the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364-79.
•
Invokana (package insert). Janssen Pharmaceuticals, Inc. Titusville, NJ. March 2013; http://www.invokanahcp.com/. Accessed: 08/28/13.
•
Stratton IM, Adler AI, Neil HAW, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS
35): prospective observational study. BMJ. 2000;321:405-12.
•
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group. Effects of intensive glucose lowering in type 2 diabetes. NEJM.
2008;358(24):2545-59.
•
The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Collaborative Group.
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. NEJM. 2008;358(24):2560-72.
84
References (continued)
•
Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. NEJM. 2009;360(2):129-39.
•
Ray KK, Kondapally Seshasai S, Wijesuriya S, et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with
diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet. 2009;373:1765-72.
•
Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death,
and microvascular events in type 2 diabetes: a meta-analysis of randomised control trials. BMJ. 2011;343:d4169 doi:10.1136/bmj.d4169.
•
Hemmingsen B, Lund SS, Gluud C, et al. Intensive glycaemic control for patients with type 2 diabetes: systemic review with meta analysis and trial
sequence analysis of randomised clinical trials. BMJ. 2011;343:d6898 Doi: 10.1136/bmj.d6898.
•
Ismail-Beigi F, Moghissi E, Tiktin M, et al. Individualizing glycemic targets in type 2 diabetes mellitis: implications of recent clinical trials. Ann Intern
Med. 2011;154:554-9.
•
Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and
2-drug combinations. Ann Intern Med. 2011;154:602-13.
•
Matthews JE, Stewart MW, De Boever EH, et al. Pharmacodynamics, pharmacokinetics, safety, and tolerability of albiglutide, a long-acting glucagonlike peptide-1 mimetic, in patients with type 2 diabetes. J Clin Endocrinol Metab. 2008;93:4810-4817.
•
Garber AJ, King AB, Del Prato SD, et al. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with
mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomized, open-label, treat-to-target non-inferiority trial. Lancet.
2012;379:1498-507.
•
Nisly SA, Kolanczyk DM, and Walton AM. Canagliflozin, a new sodium – glucose cotransporter 2 inhibitor, in the treatment of diabetes. Am J HealthSyst Pharm. 2013;70:311-9.
•
Tucker ME. FDA rejects Novo Nordisk’s Insulin Degludec. Medscape News. Accessed February 12, 2013. Available at:
http://www.medscape.com/viewarticle/779077
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