1. health and fitness
2. disease
3. diabetes

Update on Diabetes Medications and
Guidelines in Cardiopulmonary Rehab Setting
Raja Hanania, R.Ph, CDM, CDE, BCPS
Clinical Pharmacy Specialist
Critical Care/Diabetes Care
IU-Health- Bloomington Hospital
Bloomington-Indiana
Objectives
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Learn about the impact of diabetes in the United States
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Review oral and injectable diabetes medications and
their role in diabetes management
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Review the 2013 ADA general recommendations with
special emphasis on physical activity and exercise in the
cardiopulmonary rehab setting
National Diabetes Estimates
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25.8 million Americans (8.3% of the US
population)
7 million undiagnosed
79 million American adults aged 20 years or
older qualify as being at high risk to develop
diabetes (fasting glucose between 100 and
125)
If the trend continues, 1-in-3 American
adults will have diabetes by 2050
The 7th leading cause of death in the US
The leading cause of blindness, renal
failure and nontraumatic amputations
between the age of 20-74
Cost: U.S. national economic burden of prediabetes and diabetes reached $245 billion
in 2012, $218 billion in 2007 , $132 billion in
2002 vs. $44 billion in 1997
CDC National Diabetes Fact Sheet 2011.
ADA diabetes Statistics 2013
Making the Diagnosis
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Fasting Plasma Glucose Test
99 or below = Normal
100 to 125 = Pre-diabetes (impaired fasting glucose (IFG))
≥ 126 = Diabetes
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Oral Glucose Tolerance Test (OGTT)
2 hr plasma glucose result:
139 and below =Normal
140-199 = Pre-diabetes (impaired glucose tolerance (IGT))
200 and above = Diabetes
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Random Plasma Glucose Test
200 or more plus presence of symptoms (polydypsia/polyuria/polyphagia) =
Diabetes
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Results should be confirmed by repeating the
test on another day prior to diagnosis
A1c ≥ 6.5% (new 2010 criteria for diagnosis)
Classification of Diabetes
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Insulin-Dependent Diabetes Mellitus (Type I)
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High anti-beta cell antibodies
Low plasma insulin concentration (determined by C-peptide levels)
Usually lean and young patients but this trend in changing
Non-Insulin-Dependent Diabetes Mellitus (Type II)
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Serum insulin levels normal or elevated but still have relative insulin
deficiency
Metabolism does not respond properly to insulin= insulin resistance
Usually obese (60-90%) and older but thins trend is changing
Losing weight frequently brings glucose levels and insulin sensitivity
back under control
Strong genetic linkage
Classification of Diabetes (Cont.)
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Type 1.5 Diabetes (also known as slow onset type I or latent
autoimmune diabetes in adults)
– Patients do not immediately require insulin for treatment
– Little or no resistance to insulin
– Antibodies present (especially GAD65)
– Can be easily misdiagnosed as Type II since patients are older and
respond to oral medications except glitazones (since little or no
insulin resistance) & usually have good C-peptide levels
Gestational Diabetes (GD)
– In most cases, slender and physically fit patients
– Approximately 4% of all pregnancies according to ADA
– 5-10% of women with GD are found to have type 2 diabetes
– Women with GD have 20-50% chance to develop diabetes in the
next 5-10 years
Type 3 Diabetes??
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Alzheimer’s can be associated with low
levels of insulin in the brain is the reason why
increasing numbers of researchers have
taken to calling it Type 3 diabetes, or
"Diabetes of the Brain“
In Alzheimer’s, the brain, especially parts that
deal with memory and personality, become
resistant to insulin. Research is ongoing and
there will be more to come on the link
between diabetes and the brain.
Risk Factors
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Family History
Obesity: 20% over IBW or BMI > 27
Age: over 45 years old
History of impaired glucose tolerance or impaired
fasting glucose
Hypertension
HDL < 35 and/or TG > 200
Smoking
Race/Ethnicity
Pregnancy
Clinical Practice Recommendations
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ADA
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Begin screening at age 45
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Preprandial BG 70-130
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2 hr postprandial <180
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Average bedtime BG 100-140
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A1c goal <7% for patients in
general, EAG= (28.7x A1c) - 46.7
(6%= 126 mg/dl, 7%= 154, 8%=
183, 9%= 212, etc.)
ADA= American Diabetes Association
AACE= American Association of Clinical Endocrinologists
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AACE
Begin screening at age 30
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Preprandial BG 110
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2 hr postprandial <140
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A1c goal <6.5%
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Benefits of Reducing A1c by 1%
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Type I diabetes (DCCT)
-32% decrease in risk for retinopathy
-20% -27% decrease in risk for nephropathy
-30% decrease in risk for neuropathy
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Type II diabetes (UKPDS)
-10% decrease in risk in diabetes related death
- 6% decrease in all-cause mortality
-16% decrease in risk for MI
-25% decrease in microvascular complications
DCCT= Diabetes Control and Complications Trial
UKPDS= United Kingdom Prospective Diabetes Study
A1C Goals Unmet in Majority of
Patients With Diabetes
10.0
12.4% have A1C >10%1
9.5
9.0
A1C (%)
20.2% have A1C >9%3
8.5
8.0
37.2% have A1C >8%
7.5
64.2% of patients with type
2 diabetes have A1C 7%2
7.0
6.5
ACE recommended target (<6.5%)4
6.0
Upper limit of normal range (6%)
5.5
1. Data from Saydah SH, et al. JAMA. 2004; 291:335-342
2. Calculated from Koro CE, et al. Diabetes Care. 2004; 27:17-20
3. Data from ADA. Diabetes Care. 2003; 26(suppl 1):S33-S50
4. Data from ACE. Endocrine Practice. 2002
Diabetes Management
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Control of A1c, fasting glucose(FG) and postprandial
glucose levels (PPG) (DECODE study showed that PPG is
more predictive than AIC and FG for CV risk*)
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Hypertension-goal is <140/80 mmHg
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Dyslipidemia (General Guidelines):
*LDL<100 mg/dl
*HDL men >40 mg/dl, women >50 mg/dl
*Triglycerides<150 mg/dl
*Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe (DECODE)
Review of Oral Hypoglycemic Meds
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Sulfonylureas
Meglitinides
Thiazolidinediones
Biguanides
Alpha-Glucosidase Inhibitors
Dipeptidyl Peptidase IV inhibitors (DPP 4 inhibitors)
Sodium Glucose Co-transporter 2 Inhibitor (SGLT-2
inhibitor)
Combination Products
Others: Welchol and Cycloset
Sulfonylureas
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Stimulate insulin production from pancreas
Glyburide (Diabeta®, Micronase®, Glynase®), max. dose
20 mg/day
Glipizide (Glucotrol®)-taken 30 min before eating, max.
dose 40 mg/day, (Glucotrol XL®)-may be taken with food,
max. dose 20 mg/day
Glimipiride (Amaryl)-taken with food, max dose 8 mg/day
Watch for renal dysfunction:
-Glyburide not recommended for CrCl<50 ml/min,
contraindicated for patients with severe renal failure
-Glimipiride < 30ml/min, start with 1 mg daily and adjust
-Glipizide < 10ml/min use a conservative dose & adjust
Side effects-hypoglycemia, GI effects and sun sensitivity
Meglitinides
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Stimulate insulin production from pancreas
Repaglinide (Prandin®)-Max. dose 4 mg tidqid
Nateglinide (Starlix®)-Max. dose 120 mg tid
To be taken 15-30 min before meals
Skip doses for skipped meals
Side effects: hypoglycemia and GI effects
Thiazolidinediones (TZDs)
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Decrease insulin resistance, promote skeletal
muscle glucose uptake
Rosiglitazone (Avandia®)-taken with meals once or
twice daily. Max. dose 8 mg/day
Pioglitazone (Actos®)-taken once daily. Max. dose 45
mg/day
Monitor LFTs every 2 months for the first year of
therapy then periodically.
Not recommended if LFTs >2.5 times upper limit or
for NYHA class III or IV CHF patients
Side effects: Edema (secondary to plasma volume
expansion), GI effects, weight gain and back pain
Biguanides
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Decrease production of glucose in the liver, decrease
glucose absorption & improve insulin sensitivity
Metformin (Glucophage®, Glucophage XR®, Fortamet®,
Riomet® (liquid metformin))- Max dose 2550 mg/day
Used first line for obese diabetics
May also be used for polycystic ovary syndrome (PCOS)
(Not FDA approved for that indication)
Should be taken with food
Contraindicated in symptomatic CHF patients and
renal patients (SCr >1.5 men, SCr>1.4 women)
Must be discontinued for 48 hrs after any IV dye
procedure due to risk of lactic acidosis
Side effects: Nausea, diarrhea and gas that tend to
improve with continued use
Alpha-Glucosidase Inhibitors
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Slow the digestion and absorption of carbohydrates
Acarbose (Precose®), Miglitol (Glyset®)
Good for lowering post-prandial glucose
Contraindicated in patients with cirrhosis ,colon
ulcerations, DKA, inflammatory bowel disease and
patients with bowel obstruction
Usual dose 25,50 or 100 mg tid
To be taken with first bite of meal
Side effects: gas, diarrhea and abdominal pain (tend
to improve with continued use)
DPP- IV inhibitors : Januvia (sitagliptin),
Onglyza (saxagliptin), Tradjenta (linagliptin)
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A relatively new class of oral antidiabetic drugs known as
dipeptidyl peptidase-IV (DPP-IV) inhibitors
The DPP-IV enzyme normally rapidly inactivates the gut
hormone (GLP-1) so that additional insulin secretion is not
prolonged more than necessary.
Slow the inactivation of that gut hormone, therefore
increase insulin release and decrease glucose release by
the liver-prolong homeostasis
May be taken with or without food
Low sugar reactions are rare since they work in a glucose
dependent fashion
Invokana® (canagliflozin)
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Drug Class: Sodium Glucose Cotransporter 2
Inhibitor (SGLT-2 inhibitor)
Works by blocking the body’s reuptake of
filtered glucose in the kidneys leading to an
increased amount of urinary excretion of
glucose
A typical starting dose of canagliflozin is
100mg orally once a day taken before the first
meal
More on Canagliflozin…
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Doses can be increased to a maximum daily
dose of 300mg/day
Most common side effects: increased
urination, and increased urinary tract
infections/genital yeast infections in females
May cause increased thirst, constipation and
nausea
Report symptoms of low blood pressure to
Physician
Bile Acid Sequestrants:
Welchol® (colesevelam)
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Decreases blood sugar in Type II diabetics by an
unknown mechanism. Originally used for high
LDL cholesterol
Main side effect is constipation. May cause
increased triglycerides
May interfere with absorption of other
medications and must be separated from them by
at least 1 hour
Cycloset® (Bromocriptine)
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The first drug for type 2 diabetics that targets the body’s dopamine
activity
Mechanism of Action: Generally unknown , but preclinical studies
have shown brain dopamine activity to be low in metabolic disease
states which may contribute to insulin resistance
Indication: Treatment of type 2 diabetes most likely in combination
with all other existing agent
Dosage : Initial dose 0.8 mg (one tablet) taken within 2 hours of
waking with food. Dose titration weekly by 0.8 mg until clinical
effectiveness or a maximum dose of 4.8 mg is reached
Contraindications: Patients with syncopal migraines, pregnant
and nursing women, use with other dopamine receptor agonists
and pediatric patients
Bile Acid Sequestrants:
Welchol® (colesevelam)
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Decreases blood sugar in Type II diabetics by an
unknown mechanism. Originally used for high LDL
cholesterol
Main side effect is constipation. May cause increased
triglycerides
May interfere with absorption of other medications
and must be separated from them by at least 1 hour
Combination Products
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Glucovance® = Glyburide + Metformin
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Metaglip® = Metformin+ Glucotrol
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Avandamet® = Avandia + Metformin
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Actoplus Met® = Actos + Metformin
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Avandaryl® = Avandia+ Amaryl
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Duetact® = Actos + Amaryl
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Janumet® = Januvia+ Metformin
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Prandimet ® = Prandin + Metformin
Kombiglyze ® = Onglyza + Metformin
Juvisync ® = Januvia + Zocor
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Symlin® (Pramlintide)
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Symlin (pramlintide) is an injectable synthetic
analog of human amylin, a hormone that is
not present in diabetics.
It slows gastric emptying, lessens after meals
glucagon secretion and suppress appetite
May be given as a subcutaneous injection in
Type I and Type II diabetics as an add on
therapy to meal time insulin
May cause Nausea/vomiting and add to risk
of hypoglycemia especially in type I diabetics
GLP-1 agonists: Byetta® (exenatide) ,
Victoza® (liraglutide) and Bydureon®
(exenatide LA)
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Stimulate insulin secretion in a glucose-dependent
fashion
Slows the movement of food in the stomach (gastric
emptying).
Slows sugar (glucagon hormone) secretion during
hyperglycemia
May have some potential in stimulating regeneration
of the cells that make insulin (beta cells)
Over The counter Medications of
Concern with Diabetes
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Vitamins & Minerals
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Calcium 1000 - 1500 mg + Vitamin D daily
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Approximately 3 glasses of milk
Multivitamin or additional supplements as needed to balance
diet
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Decongestants (pseudoephedrine) - prolonged use can increase
blood pressure and decrease circulation
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Watch for sugar and alcohol content (especially in cough syrups)
 Many products are available sugar free and alcohol freeDiabetic Tussin & Codimal DM
Herbals and Nutraceuticals
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Consult doctor prior to use
Check glucose before and after you take,
routinely for first few weeks, then periodically
Use caution with all herbals, especially:
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Ginseng
Ma Huang or Ephedra
Glucosamine
Ginger
Nettle
Garlic
Cholesterol Medications
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Total cholesterol goal is < 200, LDL<100, HDL for
men>45, for women>55 and triglycerides <150
Have been shown to cut down on the incidence of
heart attacks and strokes in diabetics
May delay the initiation of insulin in Type II diabetics
Take at bedtime and avoid grapefruit and grapefruit
Juice
Monitor liver function tests
Side effects to tell the doctor about include: muscle
weakness, skin rash, nausea, vomiting, diarrhea and
loss of appetite
Cholesterol Medications (Cont.)
• Statins (Crestor, Zocor, Lipitor, etc.):
raise HDL; lower LDL
• Niacin: lowers LDL: increases HDL
• Bile Acid Resins (Questran, Welchol):
lower LDL
• Fibrates (Lopid, Tricor): lower
triglycerides; increase HDL
• Ezetimibe (Zetia): lowers LDL
Blood Pressure Medications
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Blood pressure goal is 140/80 for diabetics (New 2013
goal ! (lower for some)
Blood pressure control has shown to decrease
cardiovascular disease, stroke, and kidney damage in
diabetics
Lifestyle changes may be adequate for some
Some diabetics are started on blood pressure
medications called ACE Inhibitors or Angiotensin
Receptor Blockers which offer kidney protection as well
There are many different classes of blood pressures
medications for your doctor to choose from
2012 ADA/EASD Guidelines for T2DM Management Algorithm
AACE/ACE Consensus Statement Endocrine Practice 2009; 15 (No. 6)
What to do when OADs fail to maintain
control in Type 2 diabetes
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Reemphasize that diet and exercise can
produce at most a 1% reduction from
baseline; maximum effect is at 3 months
If on 2 first-line oral therapies, a third oral
agent will result in a further reduction of A1c
levels of only 1% or less
Do not add a third oral agent if A1c> 9 %
since most patients will not reach target level.
It is time to consider insulin!
Insulin Fundamentals
1.
2.
3.
Think about insulin therapy as
having three components:
Basal insulin : what you need when
not eating(between meals)
Prandial insulin: to cover food
Correction insulin: to fix abnormal
glucose levels
Characteristics of Insulin
Rapid acting Insulin such as Novolog, Humalog or Apidra
Onset: 10-15 min
Peak: 30-90 min Duration: 6-8 hrs
Fast acting Insulin such as Novolin R or Humulin R
Onset : 30 min
Peak : 2-4 hrs
Duration 8-12 hrs
Intermediate Acting Insulin such as Novolin N or Humulin N
Onset :1-2 hrs
Peak: 4-12 hrs
Duration 18-24 hrs
Basal (long acting Insulin) such as Lantus or Levemir
Onset: 1-2 hrs
No Peak
Duration: Up to 24 hrs
Mixed Insulin such as Humulin or Novolin 70/30, Novolog Mix 70/30,
Humalog 75/25, Humalog 50/50
Treatment of Hypoglycemia
Things to inform patients:
What is an insulin reaction (hypoglycemia) and
how is it treated??
 Blood
glucose becomes too low (below 70
mg/dl for most people)
 Signs - cold sweat, dizziness, fatigue, nausea,
hunger, vision changes, rapid heart rate
 Treatments - glucose tablets (3-4), glass of
milk, juice (1/2 cup), soft drink (1/2 can)
 Test your glucose again after 15 minutes, and
repeat treatment if still below 70 mg/dl
 Notify your physician!!
Recommendations:
Medical Nutrition Therapy (MNT)
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Individuals who have prediabetes or diabetes
should receive individualized MNT as needed
to achieve treatment goals, preferably
provided by a registered dietitian familiar with
the components of diabetes MNT
In general,
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Carbs 45-65%of total daily calories
Fats 25-35% of total daily calories (<7% saturated)
Protein 12-20 % (kidney disease <10%)
ADA. V. Diabetes Care. Diabetes Care 2012;35(suppl 1):S21.
Lose weight if body
mass index (BMI)>25
ADA Recommendations: Physical
Activity
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Advise people with diabetes to perform at least
150 min/week of moderate-intensity aerobic
physical activity (50–70% of maximum heart
rate), spread over at least 3 days per week
with no more than 2 consecutive days without
exercise
In absence of contraindications, people with
type 2 diabetes should be encouraged to
perform resistance training at least twice per
ADA. V. Diabetes Care. Diabetes Care 2012;35(suppl 1):S25.
week
Why Exercise?
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↑ maximal O2 uptake
↑ cardiac output
↓ resting heart rate
↓ blood pressure
↑ metabolism
↑ muscle mass
↑ capillary density of muscle
↑ mitochondrial density of muscle
↑ HDL cholesterol
↑ muscle strength
↑ endorphins
↑ self esteem
↓ shortness of Breath
↓ risk of heart disease & stroke
↑ insulin sensitivity
↑ glucose uptake
Benefits
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Counteracts osteoporosis
Counteracts obesity
Improved structure &
function of ligaments,
tendons & joints
Improved blood
glucose control
Improve endurance
Challenges!!
HEALTH
CARE
LOGIC!!
Process and Assessment
Cardiac Rehab
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Patient enters certified facility via
physician referral
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Graded Exercise Test (optional)
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Assessment:
– Cardiovascular anatomy,
physiology, physiology
– Physical examination
– Risk factor profile / risk reduction
options
– Learning preferences, barriers,
individual goals
Diabetes Self Management
Education (DSME)
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Patient enters certified facility via
provider referral
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Assessment:
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Family history - diabetes,
complications
– Duration of diabetes, current
complications (short & long term)
– Current knowledge, skills,
understanding, beliefs of diabetes
– Learning preferences, barriers,
individual goals
Interventions
Cardiac Rehab
• Monitored exercise training/
physical activity
• Self management skills:
– Blood pressure
– Lipids
– Tobacco cessation
– Weight control
– Diabetes
– Psychological – social
issues
• Counseling:
– Psychosocial
– Nutrition
DSME
AADE 7 self care
behaviors
– Eating Healthy
– Being Active
– Taking medications
– Monitoring
– Problem solving
– Reducing risks
– Health Coping
Diabetes Complications…. and
Cardiac Rehab
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People with DM are 2-4 times more likely to have CV
disease, hypertension and dyslipidemia
People with DM are susceptible to autonomic
neuropathy so may be less likely to have symptoms
during exercise (such as angina to reflect myocardial
ischemia)
People with DM may have developed long-term
complications that may make rehab more
challenging such as peripheral vascular disease and
significant claudication
Glucose Monitoring in
Cardiac Rehab
• No evidence-based guideline on a specific number of times
blood glucose should be measured in the CPR setting
• Glucose monitoring establishes patterns for glucose response and
potentially prevent hypoglycemia
• Glucose monitoring determines how often a individual should
tests BG based on his/her medications, co-morbid conditions,
medical history, meal plan, time of exercise, and history of
hyperglycemia and hypoglycemia
• Glucose monitoring assess patient’s knowledge and ability to
perform accurate blood glucose checks
Pre Exercise Hypoglycemia Care
Journal of Cardiopulmonary Rehabilitation and Prevention 2011;32:101-112
Post Exercise Hypoglycemia Care
Journal of Cardiopulmonary Rehabilitation and Prevention 2011;32:101-112
Pre Exercise Hyperglycemia for
Patients with Type 1 Diabetes
Journal of Cardiopulmonary Rehabilitation and Prevention 2011;32:101-112
Pre Exercise Hyperglycemia for
Patients with Type 2 Diabetes
Journal of Cardiopulmonary Rehabilitation and Prevention 2011;32:101-112
Post Exercise Hyperglycemia Care
Journal of Cardiopulmonary Rehabilitation and Prevention 2011;32:101-112
In Summary…
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Regular exercise helps maintain appropriate
BG levels and is a primary indication in the
management of DM
The cardiopulmonary rehab setting
represents an excellent opportunity for health
care providers to monitor and manage DM
Aerobic and strength training exercise may
trigger hypoglycemia in people with DM
Collaboration between health care providers
is key for success!!
THANK YOU!
QUESTIONS???
[email protected]