2/17/2016. Objectives. Define. Hey Sugar! DMII Management in Hospice Care

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1 Hey Sugar! DMII Management in Hospice Care Michelle Huber, R.Ph., PharmD.,CGP Objectives Review treatment for hyperglycemia discussing how these medications work, hypoglycemia risk, special considerations. Discuss treatment objectives in different groups of patients Apply knowledge to hospice patient care. Define Hyperglycemia Fasting plasma glucose Random plasma glucose Hemoglobin A1C Hypoglycemia American Diabetes Association Standards of Medical Care

2 Test your Knowledge Is glucose reabsorbed in the kidneys? At what blood glucose level does glucose start to spill into the urine? Test your knowledge When glucose spills into the urine, it may cause symptoms of? Which are symptoms of hyperglycemia? Increased thirst Increased urination Fatigue Pale complexion Dry mouth Trembling Agitation Confusion Sweet odor to breath Weight loss 2

3 How does it change in the elderly? Symptoms may be masked More difficult to diagnose Example: Warning signs like increased thirst, frequent urination and vision problems may be overlooked because of the common affects of aging on the body. For example, a normal decrease in thirst due to age can offset the typical increased thirst experienced by people with diabetes. Changes such as mental confusion, incontinence and other health complications related to diabetes are more often the presenting symptoms. Test your Knowledge Risk factors for Hypoglycemia in Older Adults Risk Factors for Hypoglycemia in Older Adults Advanced age Alcohol Cognitive impairment Complex drug regimens Hepatic dysfunction Hypoglycemia unawareness Other illnesses Polypharmacy Poor nutrition Recent hospitalization Renal insufficiency Sedative agents Insulin/ secretagogues Tight glycemic control 3

4 Which are symptoms of hypoglycemia? Which are most common in the elderly? Cold, clammy skin Trembling Feelings of nervousness Lack of motor coordination Fatigue Irritability Confusion Delirium Blurred vision Headache Dizziness Nausea Stomach pain Fainting Unconsciousness Weakness Anger, stubborness hypoglycemia unawareness frequently have low blood glucose episodes (which can cause you to stop sensing the early warning signs of hypoglycemia) have had diabetes for a long time tightly control their diabetes (which increases your chances of having low blood glucose reactions) Test your knowledge Can patients have symptoms of hypoglycemia when blood glucose levels are above 70mg/dl? 4

5 How to treat hypoglycemia? grams of glucose or simple carbohydrates Recheck your blood glucose after 15 minutes If hypoglycemia continues, repeat. Once blood glucose returns to normal, eat a small snack if your next planned meal or snack is more than an hour or two away. 15 Grams of Simple Carbohydrates Commonly Used: Glucose tablets Glucose gel tube 2 tablespoons of raisins 4 ounces (1/2 cup) of juice or regular soda (not diet) 1 tablespoon sugar, honey, or corn syrup 8 ounces of nonfat or 1% milk Hard candies, jellybeans, or gumdrops (see package to determine how many to consume Review of Antidiabetic medications Thiazolidinedione Sulfonylurea SGLT2-inhibitors Incretin mimetic DPP-4 Inhibitors Biguanides Insulin 5

6 Thiazolidinedione Rosiglitazone (Avandia) Pioglitazone (Actos) Enhance insulin sensitivity in muscle and fat by increasing glucose transporter expression Good, Bad, and the Ugly Low risk of hypoglycemia. Pioglitazone may improve lipid profile. Risk of fluid retention and CHF. Avoid in patients with symptomatic CHF; contraindicated with NYHA Class III, IV heart failure. Rosiglitazone may increase risk of myocardial infarction. Sulfonylurea- second generation Glimepiride Glipizide Glyburide Stimulates pancreatic insulin secretion 6

7 Hypoglycemia risk Elimination half-life Chlorpropamide (1 st generation) 36 hrs Glyburide- incidence may reach 40%, 10 hrs Glipizide- 4-5hr Glimepiride- 5 hr Good, Bad, and the Ugly Inexpensive. Weight gain. Glyburide may be associated with more hypoglycemia. Glyburide and chlorpropamide not recommended by ADA for geriatric patients. Reduced efficacy over time. Start low and go slow: Geriatrics disease Hepatic disease Renal Sodium-glucose co-transporter 2 (SGLT2) inhibitor Canagliflozin (Invokana)alone or with metformin (Infokanamet) Dapagliflozin (Farxiga) Empagliflozin (Jardiance) Prevent absorption of glucose back into the blood stream through the kidneys 7

8 Good, Bad, and the Ugly Weight loss Expensive Use contraindicated in renal failure. Causes slight reduction of BP. Low risk of hypoglycemia with monotherapy. May increase LDL. Can cause positive urinary glucose test. Good, Bad, and the Ugly May be associated with increased risk of stroke (canagliflozin). May be associated with increased risk of bladder cancer (dapagliflozin). Do not use if egfr <45 ml/min/1.73m 2 (canagliflozin, empagliflozin) or <60 ml/min/1.73m 2 (dapagliflozin). Genital fungal infections (male and female), urinary tract infection, increased urination, hypotension Glucagon-like, peptide-1 (GLP-1) agonist or incretin mimetic Albiglutide (Tanzeum) Exenatide (Byetta) Exenatide extended-release (Bydureon) Liraglutide (Victoza) 8

9 Mechanism of action Stimulates GLP-1 receptors on pancreatic beta cells which increases production of insulin in response to high blood glucose levels, inhibits postprandial glucagon release, slows gastric emptying. (GLP-1 is an incretin hormone.) Good, Bad, and the Ugly Weight loss. Low risk of hypoglycemia. Expensive. Injectable dosage form GI adverse effects most common: nausea 28%, diarrhea 17% May be associated with pancreatitis. May be associated with renal insufficiency Not recommended severe GI diseases Dipeptidyl peptidase-4 (DPP-4) inhibitor ( gliptins ) or incretin enhancer Alogliptin (Nesina) With metformin (Kazano) With pioglitazone (Oseni) Linagliptin (Tradjenta) With metformin (Jentadueto) Saxagliptin (Onglyza) With metformin (Kombiglyze XR) Sitagliptin (Januvia) With metformin (Janumet, Janumet XR) With simvastatin (Juvisync) 9

10 Mechanism of action Inhibits degradation of endogenous incretins which increases insulin secretion, decreases glucagon secretion (glucosedependent). Good, Bad, and the Ugly Weight neutral. Low risk of hypoglycemia. Expensive. Oral dosage form. Dosage modification with renal impairment needed with sitagliptin, saxagliptin, and alogliptin. May be associated with pancreatitis. May worsen heart failure (saxagliptin, alogliptin, highest risk) Biguanide Metformin (Glucophage, Glucophage XR) Available in combination with alogliptin, glimepiride, glipizide, glyburide, linagliptin, pioglitazone, rosiglitazone, saxagliptin, sitagliptin, repaglinide, and canagliflozin. Inhibits hepatic glycogenolysis, gluconeogenesis and enhances insulin sensitivity in muscle and fat 10

11 Good, Bad and the Ugly Weight neutral. Low risk of hypoglycemia. Inexpensive Nausea, lactic acidosis Do not use in patients with renal dysfunction. Lactic acidosis risk Predisposed to hypoxemia Acute or ends stage CHF Respiratory failure End stage copd Do not use if srcr > 1.4 mg/dl for females >1.5 mg/dl for males Insulins Insulin replacement therapy Rapid acting Novolog, Humalog, Apidra Short acting Humulin R, Novolin R Intermediate Humulin N, Novolin N Long Lantus, Levemir Ultra-long acting Tresiba, Ryzodeg 11

12 Good, Bad, and the Ugly Weight gain, hypoglycemia Once prandial insulins are added, sulfonylureas should be stopped or TZD dose should be reduced or stopped. DPP-4 inhibitors or GLP-1 agonists can be continued with prandial insulin, but patients should be monitored for hypoglycemia Basal insulin can be used as part of a 3-drug combination with metformin and sulfonylurea, TZD, DPP-4 inhibitor, or GLP-1 agonist Antidiabetic agent Comparison Class A1C decrease Possible drawbacks Cost/month Insulin 1.5 or more hypoglycemia, weight gain, injectable varies Metformin 1.5 GI, caution in renal insufficiency, lactic acidosis risk <$20 Sulfonylureas 1.5 hypoglycemia, weight gain <$20 GLP 1 agonists 1.5 injectable, nausea, pancreatitis $380 Thiazolidinediones 1 weight gain, fractures, heart failure <$20 SGLT2inhibitors 1 yeast infection, UTI $340 DPP 4 inhibitors 0.7 heart failure, pancreatitis $340 Test your Knowledge Which medication classes show highest risk for hypoyglycemia? Do any medications blunt effects of hypoglycemia? Does the risk for hypoglycemia increase with number of antidiabetic medications used? 12

13 Test your Knowledge What is the HgA1C target in the general population? Does this value differ for elderly patients? Does this value differ for debilitated, elderly patients at end of life? Recommended Target Blood- Glucose Levels in Older Adults American Geriatric Society ADA In general HbA1c: 7.5-8% Do not lower <6.5% :risk of harm FPG: mg/dl HbA1c <7.5%, Bedtime BG mg/dl Healthy, few comorbidities, good functional status Multiple comorbidities, poor health, limited life, modsevere cognitive impairment HbA1c: 7-7.5% HbA1c: 8-9% FPG mg/dl HbA1c: 8% Bedtime BG mg/dl FPG mg/dl HbA1c: 8.5% Bedtime BG mg/dl A1C to estimated average glucose A1C eag % mg/dl

14 Test your Knowledge What is the purpose of keeping blood glucose in the desired range: 14

15 DMII in the older adult Intensive glucose control (HbA1c <6.5%) is generally not recommended in elderly patients as it has been associated with increase in all-cause and cardiovascular mortality, severe hypoyglycemia, weight gain. Test your knowledge It can take up to years to demonstrate a significant decrease in CAD outcomes from more stringent glycemic management. A. 5 B. 8 C. 12 D. 20 Hospice appropriate blood glucose goals Renal threshold for glucose is 200mg/dl Goals in Hospice care: Prevent hypoglycemia Prevent hyperglycemia < mg/dl No longer concerned about microvascular and macrovascular complications Microvascular benefits from tight glycemic control take 8 years to be realized and macrovascular benefits take 3 years. Improve QoL with less frequent blood glucose checks 15

16 Impact Goals of Treatment Comorbidities History of hypoglycemia Age Diabetes duration Other medications Functional status Family and community resources Frailty Dependency Physiological function Cognitive status Life expectancy Attitude Expected treatment efforts HHNS Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNS) either type 1 or type 2 diabetes high blood glucose levels caused by either a lack of insulin or the body's inability to use insulin efficiently brought on by an illness or infection. Blood sugar level over 600 mg/dl Dry, parched mouth Extreme thirst (although this may gradually disappear) Warm, dry skin that does not sweat High fever (over 101 degrees Fahrenheit, for example) Sleepiness or confusion Loss of vision Hallucinations (seeing or hearing things that are not there) Weakness on one side of the body DKA Diabetic ketoacidosis can lead to diabetic coma caused by hyperglycemia (>240mg/dl) or hypoglycemia (<70mg/dl) When your cells don't get the glucose they need for energy, your body begins to burn fat. Ketones are acids that build up in the blood and appear in the urine when your body doesn't have enough insulin High levels of ketones can poison the body. When levels get too high, you can develop DKA. DKA may happen to anyone with diabetes, though it is rare in people with type 2 16

17 DKA DKA usually develops slowly. But when vomiting occurs, this life-threatening condition can develop in a few hours. Early symptoms include the following: Thirst or a very dry mouth Frequent urination High blood glucose Then, other symptoms appear: Constantly feeling tired Dry or flushed skin Nausea, vomiting, or abdominal Difficulty breathing Fruity odor on breath A hard time paying attention, or confusion What causes DKA Not enough insulin Your body could need more insulin than usual because of illness. Not enough food. Body breaks down body fat for energy. Miss a meal Insulin reaction (low blood glucose)if testing shows high ketone levels in the morning, you may have had an insulin reaction when the level of glucose in the blood is too low (at or below 70 mg/dl). Application H.S. 84 yr., female TIIDM, CHF, CKD IV, osteoporosis Peripheral neuropathy PPS 50% Eating small meals Fasting blood glucose: 140mg/dl HbA1c 1 month ago was 7.5% Medications: Metformin 1000mg po daily Januvia 25mg po daily Lantus 10 u SC at bedtime Metoprolol tartrate 25mg po bid Furosemide 40 mg daily Lisinopril 2.5 mg po daily Roxanol 10 mg po/sl q 2 hr prn Senna S 1 tab po bid 17

18 Application H.S. 84 yr., female TIIDM, COPD, CHF, CKD V PPS 30% Eating small, infrequent meals Fasting blood glucose: 80mg/dl Medications: Metformin 1000mg po daily Januvia 25mg po daily Lantus 10 u SC at bedtime Metoprolol tartrate 25mg po bid Furosemide 40 mg po daily Lisinopril 2.5 mg po daily Roxanol 10 mg po/sl q 2 hr prn Senna S 1 tab po bid Application H.S. 84 yr., female Severe cognitive impairment Experiencing significant nausea daily PPS 30% Eating small meals, some difficulty swallowing Fasting blood glucose: 220mg/dl Humolog before meals per sliding scale Medications: Metformin 1000mg po daily Januvia 25mg po daily Lantus 10 u SC at bedtime Metoprolol tartrate 25mg po bid Furosemide 40 mg po daily Lisinopril 2.5 mg po daily Roxanol 10 mg po/sl q 2 hr prn Senna S 1 tab po bid References Vasileios A., Doupis J., The Role of Kidney in Glucose Homeostasis SGLT2 Inhibitors, a New Approach in Diabetes Treatment. Clin Pharmacol. 2013;6(5): Clinical Review: Pharmacological Management of Glycemic Control in the Geriatric Patient with Type 2 Diabetes Mellitus. The consultant Pharmacist. Vol 24. No.1, January PL Detail-Document # PHARMACIST S LETTER / PRESCRIBER S LETTER.November 2012 Lisi D., Diabetes in the Older Adult. U.S. Pharmacist. Diabetes &Pharmaceutical Care Supplement. October