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Update on Diabetes Medications and Guidelines in Cardiopulmonary Rehab Setting
Raja Hanania, R.Ph, CDM, CDE, BCPSClinical Pharmacy Specialist
Critical Care/Diabetes Care
IU-Health- Bloomington Hospital
Bloomington-Indiana
Objectives
Learn about the impact of diabetes in the United States
Review oral and injectable diabetes medications and their role in diabetes management
Review the 2013 ADA general recommendations with special emphasis on physical activity and exercise in the cardiopulmonary rehab setting
National Diabetes EstimatesNational Diabetes Estimates
• 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 pre-diabetes 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
Fasting Plasma Glucose Test 99 or below = Normal
100 to 125 = Pre-diabetes (impaired fasting glucose (IFG)) ≥ 126 = Diabetes
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
Random Plasma Glucose Test 200 or more plus presence of symptoms (polydypsia/polyuria/polyphagia) =
Diabetes
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
Insulin-Dependent Diabetes Mellitus (Type I)– 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)– 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.)
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??
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
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 RecommendationsClinical Practice Recommendations
ADA Begin screening at age 45
Preprandial BG 70-130
2 hr postprandial <180
Average bedtime BG 100-140
A1c goal <7% for patients in general, EAG= (28.7x A1c) - 46.7(6%= 126 mg/dl, 7%= 154, 8%= 183, 9%= 212, etc.)
AACE Begin screening at age 30
Preprandial BG 110
2 hr postprandial <140
A1c goal <6.5%
ADA= American Diabetes Association
AACE= American Association of Clinical Endocrinologists
Benefits of Reducing A1c by 1%
Type I diabetes (DCCT)-32% decrease in risk for retinopathy-20% -27% decrease in risk for nephropathy-30% decrease in risk for neuropathy
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
Upper limit of normal range (6%)
ACE recommended target (<6.5%)4
8.0
9.5
A1C (%)
6.0
8.5
10.0
6.5
5.5
9.0
7.0
7.5
37.2% have A1C >8%
20.2% have A1C >9%3
12.4% have A1C >10%1
64.2% of patients with type 2 diabetes have A1C 7%2
1. Data from Saydah SH, et al. JAMA. 2004; 291:335-3422. Calculated from Koro CE, et al. Diabetes Care. 2004; 27:17-20 3. Data from ADA. Diabetes Care. 2003; 26(suppl 1):S33-S504. Data from ACE. Endocrine Practice. 2002
Diabetes ManagementDiabetes Management
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*)
Hypertension-goal is <140/80 mmHg
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 MedsReview of Oral Hypoglycemic Meds
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
SulfonylureasSulfonylureas
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
MeglitinidesMeglitinides
Stimulate insulin production from pancreas Repaglinide (Prandin®)-Max. dose 4 mg tid-
qid 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)Thiazolidinediones (TZDs)
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
BiguanidesBiguanides
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 InhibitorsAlpha-Glucosidase Inhibitors
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)
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 homeostasisMay be taken with or without foodLow sugar reactions are rare since they work in a glucose dependent fashion
Invokana® (canagliflozin)
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…
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)
Decreases blood sugar in Type II diabetics by an unknown mechanism. Originally used for high LDL cholesterolMain side effect is constipation. May cause increased triglyceridesMay interfere with absorption of other medications and must be separated from them by at least 1 hour
Cycloset® (Bromocriptine)
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)
Decreases blood sugar in Type II diabetics by an unknown mechanism. Originally used for high LDL cholesterolMain side effect is constipation. May cause increased triglyceridesMay interfere with absorption of other medications and must be separated from them by at least 1 hour
Combination Products
Glucovance® = Glyburide + Metformin
Metaglip® = Metformin+ Glucotrol
Avandamet® = Avandia + Metformin
Actoplus Met® = Actos + Metformin
Avandaryl® = Avandia+ Amaryl
Duetact® = Actos + Amaryl
Janumet® = Januvia+ Metformin
Prandimet ® = Prandin + Metformin Kombiglyze ® = Onglyza + Metformin Juvisync ® = Januvia + Zocor
Symlin® (Pramlintide)
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)
Stimulate insulin secretion in a glucose-dependent fashionSlows 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
Vitamins & Minerals
– Calcium 1000 - 1500 mg + Vitamin D daily Approximately 3 glasses of milk
– Multivitamin or additional supplements as needed to balance diet Decongestants (pseudoephedrine) - prolonged use can increase
blood pressure and decrease circulation
Watch for sugar and alcohol content (especially in cough syrups) Many products are available sugar free and alcohol free-
Diabetic Tussin & Codimal DM
Herbals and Nutraceuticals
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:
Ginseng Ma Huang or Ephedra Glucosamine Ginger Nettle Garlic
Cholesterol Medications
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
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 diabeticsLifestyle changes may be adequate for someSome diabetics are started on blood pressure medications called ACE Inhibitors or Angiotensin Receptor Blockers which offer kidney protection as wellThere 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
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
Think about insulin therapy as having three components:
1. Basal insulin : what you need when not eating(between meals)
2. Prandial insulin: to cover food
3. 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 ROnset : 30 min Peak : 2-4 hrs Duration 8-12 hrs
Intermediate Acting Insulin such as Novolin N or Humulin NOnset :1-2 hrs Peak: 4-12 hrs Duration 18-24 hrs
Basal (long acting Insulin) such as Lantus or LevemirOnset: 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)
ADA. V. Diabetes Care. Diabetes Care 2012;35(suppl 1):S21.
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, – Carbs 45-65%of total daily calories– Fats 25-35% of total daily calories (<7% saturated)– Protein 12-20 % (kidney disease <10%)
Lose weight if body mass index (BMI)>25
ADA Recommendations: Physical Activity
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 week
ADA. V. Diabetes Care. Diabetes Care 2012;35(suppl 1):S25.
Why Exercise?
Challenges!!
HEALTH CARE LOGIC!!
Process and Assessment
Interventions
Diabetes Complications…. and Cardiac Rehab
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…
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!!
