8/10/17 One Size does not fit all !!! Advanced Therapeutic Options for Management of the Type II Diabetic Patient in Primary Care Carole Mackavey DNP, MSN, APRN, RN FNP-C University of Texas Health Science Center@ Houston Texas Outcomes Diabetes Type II Prevalence • Recognize and implement the best • In 2012, 29.1 million Americans, or 9.3% of the population, had diabetes. therapeutic options for advanced Diabetes Management • 1.4 million Americans are diagnosed with diabetes every year. • Understand the mechanism of action • Prevalence in Seniors: The percentage of Americans age 65 and older remains and side effects for the most common high, at 25.9%, or 11.2 million seniors (diagnosed and undiagnosed). - See diabetic agents more at: • Examine several case scenarios and discuss a plan of care for the patient. • Undiagnosed: Of the 29.1 million, 21.0 million were diagnosed, and 8.1 million were undiagnosed • Examine and discuss the role of the patient in the management of diabetes • In 2012, 86 million Americans age 20 and older had prediabetes; this is up from 79 million in 2010. http://www.diabetes.org/diabetes-basics/statistics/?referrer=https://www.google.com/ Complications/Co-Morbid Conditions • Hypoglycemia older • Hypertension • Dyslipidemia • CVD Death • Heart Attack • Stroke • Blindness and Eye Problems: retinopathy • Kidney Disease • Amputations http://www.diabetes.org/diabetes- basics/statistics/?referrer=https://www.google.com/#sthash.iSimJp8y.dpuf 1 8/10/17 Diabetes by Race/Ethnicity Things to keep in mind • Diabetes is primarily a self managed disease • The rates of diagnosed diabetes by race/ethnic background are: • Treatment decisions should be timely, rely on evidence-based guidelines, and • 7.6% of non-Hispanic whites be made collaboratively with patients based on individual preferences, • 9.0% of Asian Americans prognoses, and comorbidities. • 12.8% of Hispanics • 13.2% of non-Hispanic blacks • The patient MUST be involved in the decisions made regarding the • 15.9% of American Indians/Alaskan Natives management of their diabetes http://www.diabetes.org/diabetes-basics/statistics/?referrer=https://www.google.com/ Alpha-Glucosidase Inhibitors So Lets Review Diabetes Medication • Inhibit enzyme at intestinal brush border How do they work? • Slow absorption of carbohydrates • Usually starts working after the first dose Alpha-Glucosidase Inhibitors Examples of alpha-glucosidase inhibitors include: • Acarbose (Precose) • Acarbose- Precose. • Miglitol (Glyset) • Miglitol - Glyset. • Average A1C reduction: 0.5% to 0.8% • Voglibose. • SE: Flatulence, diarrhea, abdominal bloating • Precautions: Avoid when creatinine clearance < 25 mL per minute per 1.73 m2 (0.42 mL per second per m2) • Most effective when given with a starchy, high-fiber diet • Reverse hypoglycemia with glucose, not sucrose Alpha-glucosidase inhibitor - Wikipedia https://en.wikipedia.org/wiki/Alpha-glucosidase_inhibitor 2 8/10/17 Alpha-Glucosidase Biguanides Inhibitors • Acarbose is able to reduce body weight, improve blood pressure, lower • Decrease hepatic glucose production; increase insulin sensitivity glucose levels, decrease in the incidence of newly diagnosed cardiovascular peripherally events and attenuate both fasting and post prandial hypertriglyceridemia. • Decrease intestinal absorption of carbohydrates • Usually works after 1-2 weeks • AGIs delays complex carbohydrate digestion. This mechanism of action leads to both wanted (lowering of glycemia) and unwanted (osmotic) effects. Undigested disaccharides which remain in the intestinal lumen may cause flatulence, diarrhea and abdominal pain. Kalra, S. (2014)Alpha glucosidase inhibitors Journal of the Pakistan Medical Association, retrieved http://jpma.org.pk/full_article_text.php?article_id=6311, Biguanides Metformin • Metformin- first line drug in treatment of type II diabetes • A1C reduction: 1.0% to 1.3% • The use of metformin as first-line therapy was supported by findings from a • SE: Nausea, diarrhea, abdominal bloating • Extended-release preparations have fewer gastrointestinal adverse large meta-analysis, with selection of second-line therapies based on effects patient-specific considerations • Precautions: Estimated GFR 30 to 44 mL per minute per 1.73 m2: review use of metformin • Metformin is effective and safe, is inexpensive, and may reduce risk of • Estimated GFR < 30 mL per minute per 1.73 m2: discontinue use • Discontinue during acute illness or procedure that could predispose cardiovascular events and death patient to lactic acidosis • American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(suppl 1):S14-S80. • Powers AC, D'Alessio D. Chapter 43. Endocrine pancreas and pharmacotherapy of diabetes mellitus and hypoglycemia. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011 Metformin Metformin Liquid Metformin (Metformin Hydrochloride 500mg/5ml Oral Solution) can be • Metformin is associated with vitamin B12 deficiency, with a recent report given to improve tolerance in patients experiencing side effects at 500 mg from the Diabetes Prevention Program Outcomes Study (DPPOS) You can start of with ½ or 1 cc and gradually increase to 500 mg. suggesting that periodic testing of vitamin B12 levels should be considered in metformin-treated patients, especially in those with anemia or peripheral neuropathy. 3 8/10/17 Dipeptidyl-peptidase-4 inhibitors (DPP4) • Increase glucagon-like peptide-1 • Increase insulin secretion from β-cells and decrease glucagon secretion from α-cells in the pancreas • Medication starts to work after 1-2 weeks http://www.f6publishing.com/Pub/10.3748/v19/i15/WJG-19-2298-g001.jpg Dipeptidyl-peptidase-4 inhibitors List of FDA-approved DPP-4 inhibitors • Alogliptin (Nesina)* • Brand name Active ingredient(s) • Linagliptin (Tradjenta)* • Janumet XR sitagliptin and metformin extended release • Saxagliptin (Onglyza)* • Onglyza saxagliptin • Sitagliptin (Januvia)* • Kombiglyze XR saxagliptin and metformin extended release • AIC reduction 0.5% to 0.9% • Tradjenta linagliptin • SE: Headache, pancreatitis (rare) • 7 more rows • Precautions: Linagliptin does not require dosage adjustment in renal insufficiency • Saxagliptin dosage adjustment required when administered with concomitant CYP3A4 • FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors inhibitors • https://www.fda.gov/Drugs/DrugSafety/ucm459579.htm DPP4 Glucagon-like peptide-1 receptor agonists (GLP1) • Increase insulin secretion from β-cells and • DPP-4 inhibitors are taken orally with or without food and have once a day decrease glucagon secretion from α-cells in the dosing. pancreas • They are safer than sulfonylureas when comparing the rate of • Suppress hepatic glucose production; delay gastric hypoglycemic episodes. emptying •They do not affect weight. • Medication starts to work after 1st dose if short acting • In patients with impaired renal function, linagliptin is the only DPP-4 inhibitor and after 2 weeks if long acting like exenitide that does not require a dose adjustment. extended (Bydurion) & dulaglutide (Trulicity) • Rare hypoglycemia events http://ftp.rxeconsult.com/healthcare-articles/New-Drugs-for-Diabetes-Treatment-509/2 4 8/10/17 Glucagon-like peptide-1 receptor agonists Approved GLP-1 agonists: • Albiglutide (Tanzeum)* • Dulaglutide (Trulicity)* (Once-weekly) • exenatide (Byetta/Bydureon), approved in 2005/2012. • Exenatide (Byetta, Bydureon)* (Bydueon once weekly) • Liraglutide (Victoza)* • liraglutide (Victoza, Saxenda), approved 2010. • A1C reduction: 0.8% to 2.0% • lixisenatide (Lyxumia), approved in 2016. • SE: Nausea, vomiting, sense of fullness • albiglutide (Tanzeum), approved in 2014 by GSK. • Weight loss of 1 to 4 kg (2.2 to 8.8 lb) is likely • Precautions: Pancreatitis (rare) • dulaglutide (Trulicity), approved in 2014—manufactured by Eli Lilly. • Exenatide is not recommended if creatinine clearance < 30 mL per minute per 1.73 m2 (0.50 mL per second per m2) • Boxed warning for personal or family history of medullary thyroid carcinoma; patients with multiple endocrine neoplasia type 2 American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(suppl 1):S14-S80. Glucagon-like peptide-1 receptor agonist - Wikipedia Powers AC, D'Alessio D. Chapter 43. Endocrine pancreas and pharmacotherapy of diabetes mellitus and hypoglycemia. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011 https://en.wikipedia.org/wiki/Glucagon-like_peptide-1_receptor_ agonist GLP1 Meglitinides • Exenatide is injected under the skin twice a day or once-weekly (Bydureon) within 60 minutes prior to meals. • Close potassium channels in β-cells; • Liraglutide is injected under the skin once daily at any time of the day. • Stimulate release of insulin from the pancreas • When GLP-1 receptor agonists are used in combination with a sulfonylurea, the risk of hypoglycemia increases. • Medication starts to work after 1st dose • Clinical trial data for GLP-1 receptor agonists have shown a weight loss of 2.3 to 2.8 kg when used as monotherapy and a range of 2.6 to 2.9 kg when used in combination with metformin. • Clinical results have demonstrated liraglutide’s potential as a weight loss drug for non- diabetic, obese patients. • After 1 year, liraglutide subjects lost 5.8 kg compared to 3.8 kg in the placebo group. The liraglutide group maintained