Joshua Settle, PharmD Clinical Pharmacist Baptist Medical Center South ALSHP Fall Meeting September 30, 2016

Transcription

1 Joshua Settle, PharmD Clinical Pharmacist Baptist Medical Center South ALSHP Fall Meeting September 30, 2016

2 Objectives Describe the current information concerning newly approved medications for diabetes mellitus. Compare and contrast newly approved diabetes mellitus medications to existing therapies. Describe potential complications from new antidiabetes products. Determine appropriate dose conversions between older and newer insulin products. (Technician)

3 Disclosure I, Joshua Settle, have no actual or potential conflict of interest in relation to this program to disclose.

4 Type 1 Diabetes Mellitus Treatments Mainstay of therapy is insulin May add additional agents Pramlinitide Metformin GLP 1 agonists* DPP IV Inhibitors* *Agents are not approved for Type 1 Diabetes treatments but are being investigated Diabetes Care 2016

5 Type 2 Diabetes Mellitus Treatments Lifestyle modifications and a patient centered approach 1 st Line Options: Metformin and/or insulin A1c target not achieved after ~3 months Add a second drug A1c target not achieved after ~3 months Add a third drug A1c target not achieved after ~3 months Add injectable medications (GLP 1 receptor agonists or insulin) *Choice of medication based on patient or disease specific factors Diabetes Care 2016

6 Anticipated A1c Lowering Effects Insulins: 1.5 to 3.5% Biguanide: 1 to 2% Sulfonylureas: 1 to 2% Meglitinides: 0.5 to 1.5% Thiazolidinediones (TZDs): 0.5 to 1.4% Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors: 0.7 to 1% Glucagon Like Peptide 1 (GLP 1) Receptor Agonist: 0.5 to 1% Bile Acid Sequesterants: 0.5 to 1% Alpha Glucosidase Inhibitors: 0.5 to 0.8% Dipeptidyl Peptidase IV (DPP IV) Inhibitors: 0.4 to 0.8% Amylin agonists: 0.4 to 0.6% Dopamine 2 Agonists: 0.1% Lexi Comp 2016

7 New Agents Lixisenatide (Adlyxin) GLP 1 Receptor Agonist Not released at this time Linagliptin + Metformin (Jentadueto XR) DPP IV Inhibitor and Biguanide Empagliflozin + Metformin (Synjardy) SGLT2 Inhibitor and Biguanide

8 Considerations for New Agents Drug: Form/Strength Good Option For: Lixisenatide Subcutaneous injection 10 μg, 20 μg Hypoglycemia risk Heart failure Weight loss Linagliptin + Metformin Empagliflozin + Metformin Tablet 2.5mg/1000mg, 5mg/1000mg Tablet 5mg/500mg, 5mg/1000mg, 12.5mg/500mg, 12.5mg/1000mg Hypoglycemia risk Weight neutral Hypoglycemia risk Heart failure Weight loss Elevated blood pressure Adlyxin PI, Jentadueto XR PI, Synjardy PI, Diabetes Metab J 2015

9 Lixisenatide Counseling Points Once daily subcutaneous injection in adjunct to diet and exercise Inject dose within the hour prior to the first meal of the day Missed dose: inject dose within the hour prior to the next meal 10 μg for 14 days then increase to 20 μg daily Pre filled pen with 14 preset doses Inspect prior to use Only use if solution is clear, colorless and no particles are visible Storage: Refrigerate prior to use then keep at room temperature Do not use if frozen Discard pen after 14 days from opening Recap pen to protect from light Adlyxin PI, Clinical Diabetes 2012

10 Lixisenatide Concerns Contraindications: Hypersensitivity to the drug Major Concerns: Antibody formation GI symptoms (nausea, vomiting, diarrhea) Increased heart rate Injection site reactions Pancreatitis Renal Impairment (extensively excreted through the kidney) Thyroid tumors (studies were done in rodents) Warnings: Gastroparesis Lowers blood pressure Adlyxin PI

11 Linagliptin + Metformin Once daily tablet Counseling Points Take with food at the same time each day Avoid excessive alcohol use Caution in patients with heart failure Iodinated contrast: Suspend for 48 hours then assess egfr Jentadueto XR PI

12 Linagliptin + Metformin Concerns Contraindications: Hypersensitivity reactions Severe renal impairment egfr<30 ml/min/1.73m 2 or SCr >1.4 mg/dl (females and >1.5 mg/dl males Metabolic acidosis (including diabetic ketoacidosis) Major Concerns: Lactic acidosis Arthralgia (debilitating) Decrease in lymphocyte counts Pancreatitis Vitamin B12 deficiency Jentadueto XR PI

13 Empagliflozin + Metformin Twice daily tablet Take with food Counseling Points Avoid excessive alcohol use Cardiovascular benefits Suspend therapy with Iodinated contrast and assess egfr after 48 hours Synjardy PI, Diabetes Care 2016

14 Empagliflozin + Metformin Concerns Contraindications: Hypersensitivity reactions Moderate to severe renal impairment, end stage renal disease or on dialysis egfr<45 ml/min/1.73m 2 Metabolic acidosis (including diabetic ketoacidosis) Major Concerns: Urinary tract infections leading to urosepsis and pyelonephritis Bone fracture Ketoacidosis Genital mycotic infections Volume depletion/hypotension Increase in LDL C Impairment in renal function Lactic acidosis Vitamin B12 deficiency Synjardy PI

15 Self Assessment It can be hard to keep track of all the new agents on the market. Please identify the latest FDA approved antidiabetes medication. A. Lixisenatide B. Empagliflozin + Linagliptin C. Linagliptin + Metformin D. Alogliptin + Metformin

16 Self Assessment Which of the following have become a major concern of SGLT2 Inhibitors? A. Diarrhea B. Hypoglycemia C. Hypokalemia D. Ketoacidosis

17 New Injectable Insulins Insulin Degludec/Insulin Aspart (Ryzodeg 70/30) 70% insulin degludec/30% insulin aspart Not released in the US at this time Insulin Degludec (Tresiba FlexTouch) Insulin Degludec U 100 and U 200 Insulin Glargine (Basaglar KwikPen) Insulin Glargine 100 units/ml Not released in the US at this time

18 New Insulin Comparison Drug Onset Peak Duration Discard Insulin 5 15 min hours >24 hours 28 days Degludec/Aspart Insulin Degludec ~1 hour ~9 hours 42 hours 56 days (minimal peak) Insulin Glargine 3 hours No peak ~24 hours 28 days Do not refrigerate after opening and protect from direct heat and light. Do not use if has been frozen. Concerns: Hypoglycemia Hypokalemia Injection site reactions Fluid retention and heart failure can occur if taken with TZDs Ryzodeg 70/30 PI, Tresiba PI, Basaglar PI, Pharmacist Letter 2015 Contraindications: Hypersensitivity to the drug During hypoglycemic episodes

19 Insulin Degludec/Insulin Aspart Counseling Points and Concerns Once or twice daily dosing with any main meal Option for Type 1 or Type 2 DM trying to decrease the number of daily injections Continue short/rapid acting insulin for meals not covered Low risk of nocturnal hypoglycemia Dosing times are less strict Ryzodeg 70/30 PI, Int J Clin Pract 2016

20 Insulin Degludec Counseling Points and Concerns Once daily Ultra long acting basal insulin Similar A1c lowering effects and similar or possibly a slightly lower hypoglycemia risks versus Lantus Good for those requiring large doses of basal insulin Greater than 80 Units per day Dosed on equivalent unit per unit basis not concentrated Dosing times are less strict Dose anytime of the day but wait at least 8 hours between dosings Tresiba PI, Pharmacist Letter 2015

21 Insulin Glargine Counseling Points and Concerns Not released until December 2016 Similar pharmacokinetic profile as Lantus Once or twice daily Long acting basal insulin Anticipated to be a cheaper insulin glargine option Solution should be clear and is not intended for IV, IM or insulin pump administration Basaglar is the first insulin product approved through an abbreviated approval pathway Basaglar PI, FDA

22 Self Assessment If a patient is currently taking 50 units of insulin degludec and your formulary item is the currently available insulin glargine, what is the appropriate insulin glargine dose? A. 20 units B. 30 units C. 40 units D. 50 units

23 References Abdul Ghani M, Del Prato S, Chilton R, and DeFronzo RA. SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA REG OUTCOME Study. Diabetes Care 2016 May; 39(5): Lexi Comp, Inc. (Lexi Drugs ), Lexi Comp, Inc.; July 16, Adlyxin Package Insert. Sanofi Aventis Available at: Accessed July 18, Jentadueto XR Package Insert. Boehringer Ingelheim Pharmaceuticals, Inc Available at: eto%20xr.pdf?dmw_format=pdf. Accessed July 28, Synjardy Package Insert. Boehringer Ingelheim Pharmaceuticals, Inc Available at Accessed August 1, 2016.

24 References Son JW, Kim S. Dipeptidyl Peptidase 4 Inhibitors and the Risk of Cardiovascular Disease in Patients with Type 2 Diabetes: A Tale of Three Studies. Diabetes Metab J Oct;39(5): Reid T. Choosing GLP 1 Receptor Agonists or DPP 4 Inhibitors: Weighing the Clinical Trial Evidence. Clinical Diabetes 2012 Jan; 30(1): Ryzodeg 70/30 Package Insert. FDA Available at: f. Accessed July 12, Tresiba FlexTouch Package Insert. Novo Nordis Available at: pi.com/tresiba.pdf. Accessed July 20, Basaglar KwikPen Package Insert. Eli Lilly and Company Available at: Accessed July 20, 2016.

25 References PL Detail Document, Comparison of Insulins and Injectable Diabetes Meds. Pharmacist s Letter/Prescriber s Letter. March 2015 Kumar A, Awata T, Bain SC, Ceriello A, et al. Clinical Use of the Coformulation of Insulin Degludec and Insulin Aspart. Int J Clin Pract Aug;70(8): FDA. FDA approves Basaglar, the first follow on insulin glargine product to treat diabetes. December 16, htm.