Diabetes Medication Updates Erica Bukovich, PharmD, BC-ADM, CDE September 20, 2018

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Diabetes Medication Updates Erica Bukovich, PharmD, BC-ADM, CDE September 20, 2018 Learning Objectives Identify medication classes available for treatment of individuals with diabetes. Demonstrate understanding of factors impacting the treatment selection of diabetes medications. Identify future treatment opportunities for diabetes care. Demonstrate understanding of medication management programs and services available to individuals with diabetes. Describe the role(s) of pharmacists in diabetes management. Current Approach to Diabetes Treatment Understand Disease Implications Utilize Standards of Care and Treatment Algorithms Comprehensive Treatment Team 1

Medications available for treatment of individuals with diabetes Biguanides Decrease amount of glucose released from liver Metformin Glucophage Metformin liquid Riomet Metformin extended release Glucophage XR, Fortamet, and Glumetza Twice daily with breakfast and evening meal Once daily, typically taken in the morning Gastrointestinal: Bloating, gas, diarrhea, upset stomach, loss of appetite Lactic acidosis may occur in people with abnormal kidney or liver function. Always tell providers that it may need to be stopped when you are having a dye study or surgical procedure. Metformin is not likely to cause low blood glucose. SGLT-2 Inhibitors Inhibit SGLT-2 proteins located in the renal tubules of the kidneys which are responsible for reabsorbing glucose back into the bloodstream. ertugliflozin Steglatro canagliflozin Invokana empagliflozin Jardiance dapagliflozin Farxiga Take once a day in the morning. Dosing adjustments for reduced renal function; age considerations for use. Genital yeast infections, Urinary Tract Infections, increased urination, dehydration, and electrolyte changes. May decrease weight and systolic blood pressure. Caution use in older individuals, those prone to hyperkalemia or dehydration, or those with history of bladder cancer. Canagliflozin: Black Box warning for amputations; Bone Fracture risk Cardiovascular Benefits 2

GLP-1 Receptor Agonists Mimic the effects of the incretin hormone GLP-1 which is excreted from the intestine when eating Exenatide Byetta (twice daily) Bydureon (weekly) liraglutide Victoza (daily) albiglutide Tanzeum (weekly) dulaglutide Trulicity (weekly) semaglutide Ozempic (weekly) Injected into the upper arm, abdomen, or thigh either twice a day, once a day, or once a week. Schedule for taking the injection varies by drug. Nausea, vomiting, diarrhea, upset stomach, dizziness, headache, pancreas inflammation. Kidney failure in patients with kidney problems Black Box Warnings for Thyroid C-cell Tumor Risk; Thyroid carcinoma risks Contact provider if experience stomach pain. DPP-4 Inhibitors Improves insulin level after a meal and lowers the amount of glucose produced by body Sitagliptin Januvia Saxagliptin Onglyza Linagliptin Tradjenta Alogliptin Nesina Take once a day at the same time each day. Stomach discomfort, diarrhea, sore throat, stuffy nose, upper respiratory infection. Can be taken alone or with biguanide, sulfonylurea, or TZD. Alert provider if side effects don t go away. Do not cause low blood glucose. Thiazolidinedione TZDs makes the body more sensitive to the effects of insulin. Increases the amount of glucose taken up by muscle cells and keeps the liver from overproducing glucose Pioglitazone Actos Taken once a day at the same time each day. Swelling (edema) or fluid retention. Do not cause low blood sugar when used alone. Increased risk of congestive heart failure in those at risk. May improve blood fat levels. Talk with your provider if you have the following symptoms: nausea, vomiting, fatigue, loss of appetite, shortness of breath, severe edema or dark urine. 3

Sulfonylureas Stimulates the pancreas to release more insulin, both right after a meal and then over several hours Glimepiride Amaryl Glyburide Diabeta, Micronase Glipizide Glucotrol, Glucotrol XL Micronized glyburide Glynase Take with a meal once or twice a day. Once daily, typically taken in the morning Low blood glucose, occasional skin rash, irritability, upset stomach Hypoglycemia awareness and management: *Always carry a source of carbohydrate *Follow meal and activity program. *Contact provider if blood glucose levels are consistently low. Meglitinide and D-Phenylalanine Derivative Stimulate the pancreas to release more insulin right after a meal. Meglitinides Repaglinide Prandin D-Phenylalanine Derivatives Nateglinide Starlix Take with meals. Effects diminish If meal is skipped, quickly and they skip the dose. must be taken with each meal. May cause low blood glucose. Works quickly when taken with meals to reduce high blood glucose levels. Less likely than sulfonylureas to cause low blood glucose. Alpha-glucosidase Inhibitors Slows carbohydrate absorption into bloodstream after eating. Acarbose Precose Miglitol Glyset Take with first bite of the meal. Do not take if not eating. Gas, diarrhea, upset stomach, abdominal pain Take with meals to limit the rise of blood glucose that can occur after meals. Does not cause low blood glucose. Side effects should go away after a few weeks. If not, call your provider. 4

Bile Acid Sequestrants Works together with Colesevelam other diabetes Welchol medications to lower blood glucose. Main effect, when used either alone or with a statin, is to lower LDL cholesterol. Has blood glucoselowering effect when taken in combination with certain diabetes medications. Take once or Constipation, twice a day with a nausea, diarrhea, meal. gas, heartburn, headache. Take with liquid. Take thyroid medication or glyburide 4 hours before taking Welchol. Make provider aware of high triglycerides or stomach problems prior to starting. Interactions with glyburide, levothyroxine and contraceptives. Alert provider if side effects don t go away. Combination Products Sitagliptin & metformin (Janumet, Janumet XR) Saxagliptin & metformin (Kombiglyze XR) Alogliptin & metformin (Kazano) Dapaliflozin & metformin (Xigduo XR) Dapaliflozin & saxagliptin (Qtern) Canagliflozin & metformin (Invokamet, Invokamet XR) Pioglitazone & glimepiride (Duetact) Alogliptin & pioglitazone (Oseni) Repaglinide & metformin (Prandimet) Pioglitazone & metformin (Actoplus Met) Glyburide & metformin (Glucovance) Glipizide & metformin (Metaglip-Discontinued) Insulin Type Brand Name Onset Peak Duration Rapid-acting Short-acting Intermediateacting Long-acting Humalog Novolog Apidra *Afrezza 10-30 minutes 30 minutes - 3 hours 3-5 hours Regular (R) 30 minutes - 1 hour 2-5 hours Up to 12 hours NPH (N) 1.5-4 hours 4-12 hours Up to 24 hours Lantus Levemir Basaglar Toujeo 0.8-4 hours Minimal peak Up to 24 hours *Inhaled product 5

Factors impacting the treatment selection of diabetes medications Efficacy Potential for hypoglycemia Impact on weight Cardiovascular effects Cost Method of Administration Kidney function Side Effects Warnings Factors impacting patient adherence Cost Side effects Dosing schedule Stigma/Social implications Future treatment opportunities for diabetes care 6

Potential Developments in Diabetes Care Diabetes Classifications and Treatment Guidelines New Drugs In Development Oral GLP-1 GLP-1 and glucagon receptor agonist Oral insulin Subdermal GLP-1 implant SGLT-1 and SGLT-2 inhibitor Advances in Type 1 Medication management programs and services Pharmacy Practice 2018 Dispensing and Drug Delivery Retail or Mail Order Hospital Practice Medication Therapy Management (MTM) Vaccine Services Comprehensive Medication Reviews Disease-Specific Management Collaborative Practice Agreements (CPA) 7

Demonstrated Outcomes with Pharmacist Services Asheville Project Patient Self-Management Program for Diabetes (PSMP) Diabetes Ten City Challenge (DTCC) Diabetes Therapy Management Insulin Dosing and Administration Medication Management Blood Glucose Testing and Supplies Treatment and Side Effect profiles of medications Pharmacist Interventions for People with Diabetes With Providers: Promote Evidence Based Medicine Product Selection Drug Monitoring Source: www.pharmacy-tech-resources.com and ADA With Individuals: Identify Education Needs Educate on Medication Delivery Side Effect Management 8

Opportunities to Coordinate with Pharmacists Drug Delivery Education Medication Management Immunizations Disease Management Source: Drug Topics References The Asheville Project: Long-Term Clinical and Economic Outcomes of a Community Pharmacy Diabetes Care Program. J Am Pharm Assoc. 2003;43:173 84. Assessing the Effect of Pharmacist Care on Diabetes-Related Outcomes in a Rural Outpatient Clinic. Retrieved from http://journals.sagepub.com/doi/full/10.1177/1060028016685731 Collaborative Practice Agreements and Pharmacists Patient Care Services Retrieved from https://www.cdc.gov/dhdsp/pubs/docs/translational_tools_pharmacists.pdf Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm 2018 Executive Summary. Endocr Pract.2018. doi:10.4158/cs- 2017-0153 Estimated Cost-Effectiveness, Cost Benefit, and Risk Reduction Associated with an Endocrinologist-Pharmacist Diabetes Intense Medical Management Tune-Up Clinic. Retrieved from http://www.jmcp.org/doi/full/10.18553/jmcp.2017.23.3.318 Standards of Medical Care in Diabetes 2018. https://doi.org/10.2337/dc18-sint01. Diabetes Care 2018;41(Suppl. 1):S1 S2. 9