Making Sense of Mediations for Diabetes

Transcription

1 Making Sense of Mediations for Diabetes Lisa Kroon, PharmD, CDE Professor of Clinical Pharmacy UCSF School of Pharmacy Diabetes Mellitus: U.S. Impact Source: ADA; released June 10, 2014 ~1-1.5 Million Type 1 (5%) DIABETES 29.1 Million Pre-Diabetes (9.3%) 86 Million (37%; people age 20 and older) 2/3 Diagnosed ~28 Million Type 2 1/3 Undiagnosed (8.1 Million) Obesity (BMI 30 kg/m 2 ) 1994 Diabetes Age-Adjusted Prevalence of Obesity and Diagnosed Diabetes Among U.S. Adults Aged 18 Years or older No Data <14.0% % % % >26.0% Medications for Type 2 Diabetes o Biguanides (metformin) o Sulfonylureas o Meglitinides o Thiazolidinediones o Alpha glucosidase inhibitors o DPP 4 inhibitors o GLP 1 receptor agonists o Amylin mimetics (pramlintide) o Bile acid sequestrants (colesevelam) o Dopamine 2 agonists (bromocriptine) o Insulin No Data <4.5% % % % >9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at 1

2 Glycemic Goals o HbA1c < 7.0% (mean PG mg/dl) o Pre prandial PG <130 mg/dl (7.2 mmol/l) o Post prandial PG <180 mg/dl (10.0 mmol/l) o Individualization is key: Tighter targets ( %) younger, healthier Looser targets (< %+ ) older, comorbidities, hypoglycemia prone, etc. o Avoidance of hypoglycemia Diabetes Care Jun;35(6): doi: /dc Epub 2012 Apr 19. Pieces of the Diabetes Puzzle Insulin/Medication Food/Carbohydrate Healthy Eating Blood Glucose Monitoring Exercise/Physical Activity Weight optimization T2DM Anti hyperglycemic Therapy: General Recommendations Diabetes Care. 2012;35: ] 2

3 Management of Hyperglycemia in Type 2 Diabetes: A Patient Centered Approach Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Initial drug monotherapy Efficacy Hypoglycemia Weight Side effects Costs Healthy eating, weight control, increased physical activity Metformin High Low risk Neutral/loss GI/lactic acidosis low If needed to reach A1C target after ~3 months, Proceed to 2 drug combination therapy Sulfonylureas (SFUs) o Available for use since the late 1950 s o Commonly used SFUs: glyburide, glipizide, glimepiride o Stimulate the pancreas to release insulin o Dosing Taken once or twice daily Start with low dose and increase as required for glucose control o Some SFUs are preferred in patients with kidney disease Diabetes Care. 2012;35: Meglitinides (glinides) o Non sulfonylurea insulin secretagogues Repaglinide, Nateglinide o Stimulate the pancreas to release insulin o Fast acting and help control BS after a meal o Taken right before eating a meal (within 30 minutes) o Effect doesn t last as long as SFUs o Effect on FBS and A1C similar to SFUs (nateglinide less) o Option for patients with severe kidney disease or erratic eating habits Biguanides (metformin) o Decreases sugar release from the liver (hepatic glucose output) o Advantages: no weight gain, positive effect on cholesterol; no low blood sugar when used alone o Generally first choice of therapy 3

4 Metformin o Dosing Take with meals and/or at bedtime Taking with food may reduce stomach upset & diarrhea Dose is increased slowly generally to target of 1500 mg daily (therapeutic max is 2000 mg) SE: GI (diarrhea, nausea, cramping, metallic taste), lactic acidosis (incidence rate of 5 9/100,000), vit B 12 deficiency Extended release formulation available Metformin o Avoid use in: Kidney disease Active liver disease Heart failure, unstable Other serious medical problems (such as severe lung disease, blood infection, conditions of acidosis) Excessive alcohol use or alcoholism o Stop taking metformin before a diagnostic test where a contrast dye is used. Restart as instructed by doctor (usually 48 hours after test). Jan 2009 Glucophage package insert Alpha-Glucosidase Inhibitors o Acarbose, Miglitol o Delay carbohydrate digestion and slows glucose absorption from the gut o Dosing: Taken with first bite of meal; dose is increased slowly o Possible side effects: gas, diarrhea, stomach discomfort (lessen over time). No weight gain. Thiazolidinediones (TZDs) o Rosiglitazone, Pioglitazone o Improve insulin sensitivity (decrease insulin resistance) enhance glucose update by muscle and fat tissue decreases hepatic glucose output Activate PPAR (peroxisome proliferator activated receptors gamma) nuclear receptors o Slow onset to effect: take 4 6 weeks to have an effect on BS (up to 3 to 4 months) o Can work well in overweight patients o Dosing: Taken once or twice daily o Common side effects: fluid retention, weight gain 4

5 TZDs o Avoid use in: Heart failure (technically Class III & IV; some avoid in all) Severe liver problems (check liver function before starting and then periodically after ~every 6 months) o Rosiglitazone may have cardiovascular risks (increase risk of heart attack/mi) No longer under restricted access in the U.S. o Pioglitazone not available in some countries due to concern about increased risk for bladder cancer Incretins in Type 2 Diabetes o 2 main gut incretins Glucose dependent insulinotropic polypeptide (GIP) Released by K cells in duodenum Glucagon like peptide 1 (GLP 1) Released by L cells in small intestines Levels are diminished in type 2 DM post meal t 1/2 <2 minutes o Rapidly degraded by dipeptidyl peptidase IV (DPP IV) GLP 1 analogs or incretin mimetics : Exenatide, Liraglutide (injected) DPP IV inhibitors (oral): sitagliptin, saxagliptin, alogliptin, linagliptin Bloomgarden ZT. Diabetes Care 2004;27: Actions of GLP-1 o Increases insulin release (glucose dependent) o Reduces post meal levels of glucagon, which then reduces hepatic glucose output o Slows stomach empting o Promotes satiety and inhibits appetite o Preservation of beta cells Exenatide o GLP 1 analog Synthetic Exendin 4; has 53% overlap with human GLP 1 hormone Exendin 4 isolated from saliva of a lizard called the Gila monster (Heloderma suspectum) o Resistant to DPP IV degradation o Exenatide dosing Injected twice a day before (within 60 mins) morning and evening meal After 1 month, can dose o Exenatide extended release dosing injected once weekly (anytime of day) microsphere drug delivery technology Medical grade biodegradable polymer As degrades, releases drug 5

6 Exenatide o Avoid in: Not recommended in severe kidney problems (clearance <30 ml/min) Do not use in patients with severe GI disease (e.g., gastroparesis) Do not use if history of pancreatitis; stones in gallbladder, alcoholism, or significantly elevated blood triglycerides Do not use in patients with personal or family history of MTC (medullary thyroid cancer) or multiple endocrine neoplasia syndrome type 2 (MEN 2) exenatide extendedrelease Liratglutide o GLP 1 analog has 97% overlap with human GLP 1 hormone o Self associates, binds albumin, leading to increased stability and hydrolyzed by DPP 4 significantly more slowly than human GLP 1 o Dosing: taken daily; dose after 1 week o Do not use in patients with personal or family history of MTC (medullary thyroid cancer) or multiple endocrine neoplasia syndrome type 2 (MEN 2) DPP-4 Inhibitors o Inhibit DPP 4 and slows degradation of the body s incretins (GIP, GLP 1) o Sitagliptin, saxagliptin, linagliptin, alogliptin o Dosing: taken once daily o Vary with respect to caution in kidney problems and drug drug interaction potential o Advantages: oral; weight neutral; little nausea or hypoglycemia SGLT-2 Inhibitors o Inhibit sodium glucose cotransporter 2 in proximal tubules of the kidneys, where responsible for reabsorption of ~90% of glucose filtered through nephron o Canagliflozin, Dapagliflozin Dosing: taken daily Common side effects: vaginal yeast infections and UTIs (due to increased glucose in urine) Has a diuretic effect (dizziness in 1 st few months) 6

7 DPP 4 Inhibitors GLP 1 Rec. Agonists Acarbose Miglitol Metformin SFUs/Glinides GLP 1 Rec. Agonists TZDs Other Type 2 Diabetes Medications o Insulin o Amylin mimetics (pramlintide) Synthetic analog of amylin, which is co released from beta cells in pancreas Slows stomach emptying, decreases post meal glucagon levels, and promotes satiety o Bile acid sequestrants (colesevelam) mainly used to lower cholesterol Reduces hepatic glucose output o Dopamine 2 agonists (bromocriptine) Mimics the job done in the brain by a natural hormone called dopamine. In type 2 diabetes, lower levels of dopamine activity in the morning, which may interfere with the body s ability to control blood sugar. Herbs to Lower Blood Glucose o Gymnema (Gymnema sylvestre) o Bitter melon (Momordica charantia) o Indian Malabar (Pterocarpus marsupium) o Fenugreek (Trigenella foenumgraecum) o Guar Gum (karaya gum) o Nopal (prickly pear cactus) o Ginseng o Cinnamon o Don t make too many changes at once o mini study o Careful with product selection (adulteration) Diabetes Care. 2012;35:

8 Advancing to Dual Therapy Individualizing Therapy: Examples On meformin already: o SFU (or glinide) o DPP 4 inhibitor o GLP 1 receptor agonist o TZD o SGLT 2 inhibitor o Insulin (usually basal insulin) Combination Pills o Many combination pills are available, where 2 oral agents are combined into 1 pill o Can create confusion Providers unfamiliar with names not clear actually 2 medications Can lead to medication errors o If on stable dose of each medication, may be helpful (reduce # pills taken; co pays, however Brand only $$$) Diabetes Care 2012;35:

9 Adjusting Medications o Consider glycemic goals (A1C) o Take into consideration Medication adherence Changes to diet Changes to physical activity When to Make the Move to Insulin? o Glycemic goals o Assess adherence issues Lifestyle changes (diet/exercise) Medications o Other reasons for increased glucose Stress: psychosocial, infection Started medication that can worsen glucose (such as prednisone or antipsychotic agent) o Disease progression (pancreatic failure) Insulin Types Insulin Pharmacokinetics: Time-Action Profile o Rapid acting o Short acting o Intermediate acting o Long acting Injected subcutaneously: abdomen preferred 7/6/05: Lente and Ultralente no longer be available in /07: Exubera, an inhaled insulin no longer being distributed. 6/27/14: Afrezza (insulin human) Inhalation Powder approved; rapid-acting 9

10 Insulin Time Action Profile Normal BG and Insulin Levels Insulin level Rapid (Lispro, Aspart, Glulisine) Short (Regular) Intermediate (NPH) Long (Detemir) Long (Glargine) Hours Hours after injection Image: Insulin Replacement vs Secretion Image: Adding Insulin to Other Agents o o o Introduction of insulin: Add basal insulin Generally use long acting insulin (glargine, detemir) ~10 units or units/kg Self monitoring of blood glucose (hypoglycemia education) Rationale Decrease liver glucose output during night; lowers FPG Other agent controls blood glucose throughout day; maintain effect on insulin sensitivity 1 shot regimen as a transition Adjust insulin based on FPG (before 1 st meal of the day): weekly interval (no less than every 3 days) Diabetes Care. 2012;35: Nathan et al. Diabetes Care 2009;32:

11 Other Considerations o Self monitoring of blood sugar: more often o More frequent follow up with provider/patient o Self management education (hypoglycemia; how to administer insulin) o Type of insulin delivery Vial and syringe Pen device visual/dexterity problems dosing errors with syringe Pen Devices o Prefilled o Durable (insulin cartridge o Supplies: pen needles Insulin Side Effects o Local allergic reactions o Systemic allergies are rare o Lipohypertrophy: caused by repeated injections into same site o Hypoglycemia o Weight gain Insulin Storage o Refrigerate unopened vials/pens o Vials and pens in use may be kept at room temperature Pen devices should NOT be refrigerated once in use Room temperature insulin is less painful Discard after 1 month (up to 42 days for detemir) >36 F and <86 F (<77 F for glulisine) o Duration of storage at RT less for some pens/dosing devices (10 14 days) 11

12 Other Considerations o Advancing to meal time insulin Assess readiness Can start with one meal (largest) Add other meals (eventually premeal) Discontinuation of SFU What s the difference between a brand & generic medicine? o For the majority of medicines, nothing. o A generic medicine is able to be produced once the Brand medicine s patent runs out o All generic medicines are approved by the FDA and undergo strict testing o For certain medicines (such as hormones), stay with the same manufacturer to ensure a constant amount is absorbed from the gut General Medicine Tips o Keep an accurate list of all medicines you currently take and carry it with you. Include nonprescription medicines, herbs, vitamins, and dietary supplements o Bring and share your medicine list with ALL your health care providers. Bring all your medicine bottles to your visits. o Try to use only one pharmacy system so the pharmacist has a record of all your medicines (to reduce risk of duplicating medicines and harmful drug interactions). General Medicine Tips, cont. o Learn about your medicines Know the purpose of each medicine Read the label carefully Know how to take the medicine and the best time to take it Be familiar with possible side effects Know how to store your medicine Know what to do if you miss a dose 12

13 Taking Medicines Consistently o Take your medicines as instructed. If you are taking a medicine differently, inform your health care provider. o Devise a system that works for you (such as a pillbox) 13