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Diabetes Update 2016: New Drugs and New Methods of Care Kelly Murray, PharmD, BCACP Clinical Assistant Professor of Clinical Pharmacy OSU College of Osteopathic.

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Presentation on theme: "Diabetes Update 2016: New Drugs and New Methods of Care Kelly Murray, PharmD, BCACP Clinical Assistant Professor of Clinical Pharmacy OSU College of Osteopathic."— Presentation transcript:

1 Diabetes Update 2016: New Drugs and New Methods of Care Kelly Murray, PharmD, BCACP Clinical Assistant Professor of Clinical Pharmacy OSU College of Osteopathic Medicine Emergency Department Clinical Pharmacist OSU Medical Center

2 Overview  Standards of Care 2016 Updates  New Diabetes Therapies  Oral medications  Injectable medications  Insulin therapies  Innovative Care Solutions and Ideas 2

3 Objectives  Describe the mechanisms of action of the newest type 2 diabetes medications – DPP4-inhibitors, incretin mimetics, and SGLT-2 inhibitors.  Recall advantages of insulin degludec over insulin glargine.  List 3 resources to assist patients with the costs of their medications. 3

4 Standards of Care 2016 Updates

5 General Changes  “Person with diabetes” vs. “diabetic”  Support technology to assist diabetes management  Obesity management/treatment recommendations Cefalu WT. Diabetes Care 2016;29(1):S1-S112. 5

6 Testing  All adults ≥45 years old regardless of weight  Any person who is overweight/obese with ≥1 risk factor Cefalu WT. Diabetes Care 2016;29(1):S1-S112. 6

7 Diabetes Management in Pregnancy  A1c target 6-6.5% instead of 6%  Insulin or metformin > glyburide Cefalu WT. Diabetes Care 2016;29(1):S1-S112. 7

8 8

9 New Diabetes Therapies DPP-4 Inhibitors GLP-1 Agonists SGLT2 Inhibitors New Basal Insulins New Bolus Insulins

10 Where do diabetes meds work? Liver Intestines Brain Pancreas Muscle and Adipose ↓ glucose production ↑ insulin secretion ↑ satiety ↑ peripheral glucose uptake ↓ digestion and absorption of carbs Delay gastric emptying Kidneys ↓ glucose reabsorption SGLT2 inh Insulin Metformin TZDs Pramlintide DPP-4 inh. Incretin mimetics Insulin Sulfonylureas Meglitinides DPP-4 inh. Incretin mimetics Pramlintide Incretin mimetics Insulin Metformin TZDs Metformin a-glucosidase inh. Pramlintide Incretin mimetics 10

11 What level do they fix? FASTINGMIXEDPOSTPRANDIAL Interm. insulin Long insulin Regular insulin Rapid insulins Metformin SU Meglitinides TZDs a-glucosidase (-) DPP-4 (-) SGLT2 (-) Incretin mimetics (Exen.) Incretin mimetics Pramlintide 11

12 Incretin Effect  Eat food  nutrients and glucose in the gut  Intestinal mucosal cells sense this and release hormones called incretins  GLP1 = glucagon like peptide 1  GIP = glucose-dependent insulinotropic polypeptide  The “incretin effect” is decreased in type 2 diabetes, so we need to replace levels. Idris I. Diabetes Obes Metab 2007;9:153-65. 12

13 Need for Drug Therapy That:  Inhibits degradation of DPP-4 so there is more circulating incretin;  DPP-4 inhibitors OR  Replaces incretin altogether by giving an analog exogenously  Incretin mimetic, or GLP-1 receptor agonist 13

14 Dipeptidyl Peptidase - 4 (DPP-4) Inhibitors Sitagliptin (Januvia)Saxagliptin (Onglyza) + Metformin (Janumet, XR) + Simvastatin (Juvisync) + Metformin (Kombiglyze XR) Linagliptin (Tradjenta)Alogliptin (Nesina) + Metformin (Jentadueto) + Empagliflozin (Glyxambi) + Metformin (Kazano) + Pioglitazone (Oseni) Lexi-complete Online. Accessed 4/7/16. 14

15 DPP-4 Inhibitors  Mechanism:  Inhibits DPP-4 (enzyme that breaks down incretin)  Increased circulating incretin, helping control glucose absorbed in the diet  Glucose-dependent increase in insulin secretion  Glucose-dependent inhibition of glucagon secretion Idris I. Diabetes Obes Metab 2007;9:153-65. Drucker DJ. Lancet 2006;368:1696-705. 15

16 DPP-4 Inhibitors - Safety  AE:  Placebo-like: HA, URI, nasopharyngitis, UTI  Rare: pancreatitis, skin reactions, urticaria/angioedema  CI: Hx of pancreatitis, DKA, type 1 diabetes  Counseling:  With or without food Lexi-complete Online. Accessed 4/7/16. 16

17 DPP-4 Inhibitors - Efficacy  Average A1c reduction: 0.6-0.8%  Primarily acts on postprandial glucose  Remember they are glucose-dependent 17

18 DPP-4 Inhibitors  Advantages:  No hypoglycemia as monotherapy  Weight neutral  Placebo-like AE  Beta cell preservation  Linagliptin – no renal adjustments needed  Disadvantages:  Modest A1c lowering  Cost  Long term safety unknown 18

19 DPP-4 Inhibitors Dosing Guide  Sitagliptin 100mg po daily  CrCl 30-49= 50mg po daily  CrCl ≤ 30= 25mg po daily  ESRD= 25mg po daily without regard to HD  Reduce dose of concomitant insulin/secretagogues  Saxagliptin 2.5 – 5mg po daily  CrCl ≤ 50 = 2.5mg po daily  ESRD = 2.5mg po daily, post-HD  With strong CYP 3A4/5 inhibitors (“conazoles” and protease inhibitors) = 2.5mg po daily  Reduce dose of concomitant insulin/secretagogues Lexi-complete Online. Accessed 4/7/16. 19

20 DPP-4 Inhibitors Dosing Guide  Linagliptin 5mg po daily  Reduce dose of concomitant insulin/secretagogues  No renal dose adjustment needed  Alogliptin 25mg po daily  CrCl 30-59= 12.5mg po daily  CrCl 15-29= 6.25mg po daily  ESRD= 6.25mg po daily, without regard to HD  Reduce dose of concomitant insulin/secretagogues Lexi-complete Online. Accessed 4/7/16. 20

21 GLP 1 Receptor Agonists (a.k.a. incretin mimetics)  Exenatide (Byetta, Bydureon)  Liraglutide (Victoza, Saxenda)  Albiglutide (Tanzeum)  Dulaglutide (Trulicity)  Lixisenatide (Lyxumia)  App. for new drug approval submitted 9/2015 Lexi-complete Online. Accessed 4/7/16. FDA Drugs. Accessed 4/11/16. 21

22  Mechanism: GLP1 analog  Increases incretin levels  Glucose-dependent increase in insulin secretion  Glucose-dependent inhibition of glucagon  Reduces gastric emptying  Increases satiety GLP 1 Receptor Agonists (a.k.a. incretin mimetics) Lexi-complete Online. Accessed 4/7/16. 22

23  Adverse Effects:  Nausea – 8-40% more vs. placebo/comparator  Exen BID>Lira>Exen Q7D>Alb/Dula  Diarrhea – 3-118% more vs. placebo/comparator  Rare – pancreatitis, renal dysfunction, thyroid tumors  CI:  Gastroparesis  Pancreatitis  Exen: CrCl <30 (maybe others?)  Lira, Alb, Dula, Exen: PMH or FH of thyroid cancer, multiple endocrine neoplasia GLP 1 Receptor Agonists (a.k.a. incretin mimetics) Shyangdan DS. Cochrane Database Syst Rev 2011. Lexi-complete Online. Accessed 4/7/16. 23

24 GLP 1 Receptor Agonists (a.k.a. incretin mimetics)  Efficacy:  A1c reduction 1-2%  Adjunct for type 2 diabetes  BID = More postprandial reduction  Daily, Q7D Dosing = More fasting reduction Drucker DJ. Lancet 2006;368:1696-705. Lexi-complete Online. Accessed 4/7/16. 24

25 GLP 1 Receptor Agonists (a.k.a. incretin mimetics)  Dosing considerations  Inject into thigh, abdomen, upper arm  Exenatide BID 60 minutes prior to 2 main meals  Reduce incidence of nausea with proper dose titration (start low, go slow)  Once-weekly injections < twice daily injections Lexi-complete Online. Accessed 4/7/16. 25

26  Start weekly dose the day after D/C IR  D/C IR Monday, start ER Tuesday  Pt may have increased BG levels for 2 weeks  Pretreatment for this temporary rise is unnecessary Exenatide IR to ER Lexi-complete Online. Accessed 4/7/16. 26

27 GLP 1 Receptor Agonists (a.k.a. incretin mimetics)  Advantages:  Weight loss – 1-5kg  No priming after initial dose  Extended release option available  Preservation of beta cell function  Decrease insulin resistance Shyangdan DS. Cochrane Database Syst Rev 2011. 27

28 GLP 1 Receptor Agonists (a.k.a. incretin mimetics)  Disadvantages:  May reduce absorption rate and extent of drugs requiring rapid absorption (i.e. pain relievers, antibiotics, BCPs). Separate by 1 hour.  Requires subcutaneous injection  Cost  GI side effects Lexi-complete Online. Accessed 4/7/16. 28

29 GLP-1 Agonists Dosing Guide  Byetta (exenatide) 5mcg subq BID ac, increase to 10mcg subq BID after 1 month  CrCl <30= use is not recommended  Bydureon (exenatide) 2mg subq once weekly  CrCl <30= use is not recommended  Victoza (liraglutide) 0.6 mg subq once daily x 1 week, then increase to 1.2mg subq once daily. May go to 1.8mg if optimal glycemic response not achieved.  If missed doses, resume with next scheduled dose.  If >3 days of missed doses, resume with 0.6mg dose and retitrate.  No CrCl limitations on use Lexi-complete Online. Accessed 4/7/16. 29

30 GLP-1 Agonists Dosing Guide  Tanzeum (albiglutide) 30mg subq once weekly, may increase to 50mg once weekly if inadequate response at week 12.  Missed dose = administer ASAP within 3 days. If >3 days have passed, omit dose and resume with next scheduled dose.  No renal adjustment necessary.  Trulicity (dulaglutide ) 0.75mg subq once weekly; may increase to 1.5mg weekly if inadequate response.  Same missed dose regimen as albiglutide  No renal adjustment necessary.  Lyxumia (lixisenatide) – once daily prandial subq injection, dose TBA Lexi-complete Online. Accessed 4/7/16. 30

31 Incretin Mimetic vs. DPP-4 Inhibitors Incretin MimeticDPP-4 Inhibitor Delay gastric emptyingNo effect on gastric emptying Increase satietyNo increase in satiety Lots of N/VPlacebo-like AE Weight lossNo change in weight SC administrationPO administration Drucker DJ. Lancet 2006;368:1696-705. 31

32 SGLT2 Inhibitors Canagliflozin (Invokana)Dapagliflozin (Farxiga) Approved 3/13 + Metformin (Invokamet) Approved 1/14 + Metformin (Xigduo) Empagliflozin (Jardiance) Approved 8/14 + Metformin (Synjardy) + Linagliptin (Glyxambi) Lexi-complete Online. Accessed 4/7/16. 32

33 SGLT2 Inhibitors Mechanism of Action  Blocks renal absorption of ~90% of excess glucose  Causes renal wasting of glucose, lowering serum BG and A1c over time  Minimizes chance of hypoglycemia Jurczak MJ. Diabetes 2011;60:890-8. Lexi-complete Online. Accessed 4/7/16. 33

34 SGLT2 Inhibitors  Adverse Effects:  Urinary/genital infections  Hypotension  Bone fractures  DKA  Hyperkalemia  Renal insufficiency  Contraindications:  Hypersensitivity  ESRD/Dialysis Lexi-complete Online. Accessed 4/7/16. 34

35 SGLT2 Inhibitors  Counseling Points:  With or without food  Before the first meal of the day  Efficacy  0.5-0.9% A1c lowering  Mostly post-prandial glucose lowering Lexi-complete Online. Accessed 4/7/16. 35

36 SGLT2 Inhibitors  Advantages:  New mechanism, another option  Less hypoglycemia  Weight loss  Potential BP- lowering  Disadvantages:  DKA  Price / insurance coverage  May encourage diet indiscretions?  Cancer risk? 36

37 Dosing Recommendations  Canagliflozin (Invokana)  100mg po once daily before first meal of the day  eGFR 45-59 = 100mg po daily max  eGFR <45 = use is not recommended/CI  Dapagliflozin (Farxiga)  10 mg po once daily without regard to meals  eGFR <60 = use is not recommended/CI  Empagliflozin (Jardiance)  10mg po once daily without regard to meals  eGFR <45 = use is not recommended/CI Lexi-complete Online. Accessed 4/7/16. 37

38 Type 2 Therapies (Fig 7.1) Cefalu WT. Diabetes Care 2016;29(1):S1-S112. 38

39 New Insulin Therapies

40  Ideal basal insulin  Peakless  Consistent rate of absorption  No weight gain  True 24-hour coverage  Bolus insulin  Lots of injections  Titratable dose  Minimize side effects 1. Insulin degludec (Tresiba) 2. Insulin glargine (Toujeo) 3. Insulin glargine (Basaglar) 4. Humalog U-200 KwikPen 5. Inhaled insulin (Afrezza) Hess R. ACSAP 2016;1:35-64. 40

41 Insulin degludec (Tresiba) Image: https://www.diabetesdaily.com/blog/2015/09/tresiba-fda-approves-new-basal-insulin-in-the-usa/. Accessed 4/11/16.https://www.diabetesdaily.com/blog/2015/09/tresiba-fda-approves-new-basal-insulin-in-the-usa/ 1 1 41

42 Insulin degludec (Tresiba)  Long-acting insulin  Onset = 1 hour  Time to peak = 9 hours  t ½ = 25 hours  Duration = 42 hours Lexi-complete Online. Accessed 4/7/16. 42

43 Insulin degludec Mechanism  Naturally, insulin dimers form hexameric complexes to maximize storage within beta-cell vesicles  Degludec mimics this natural process  Hexamer  multihexameric chain = depot formation with a slow constant release over time Jonassen I. Pharm Res 2012;29:2104-14. 43

44 Head-to-Head: Insulin degludec vs.  Insulin glargine  Noninferiority criteria met (95% CI -0.14 to 0.11)  Nocturnal hypoglycemia rates 25% lower (p=0.021)  Mean weight gain similar (1.8 kg with degludec and 1.6 kg with glargine) (p=0.62)  Insulin detemir (+ aspart)  Noninferiority criteria met (95% CI -0.23 to 0.05)  Nocturnal hypoglycemia 34% lower (p=0.0049)  Weight gain higher with degludec (est. diff. 1.08 kg; p<0.0001) Heller S. Lancet 2012;379:1489-97. (BEGIN) Mathieu C. J Clin Endocrinol Metab 2013;98:1154-62. (BEGIN:Flex T1) 44

45 HbA1c Comparison Mathieu C. J Clin Endocrinol Metab 2013;98:1154-62. (BEGIN:Flex T1) 45

46 Insulin degludec (Tresiba)  100 units/mL and 200 units/mL available  No conversion calculation necessary; same unit per unit dose  Dosing:  Type 1: 0.2-0.4 units/kg (1/3-1/2 the TDD)  Type 2: 10 units once daily  Missed doses: administer ASAP to ensure at least 8 hours between doses  Stable at room temp for 8 weeks Mathieu C. J Clin Endocrinol Metab 2013;98:1154-62. (BEGIN:Flex T1) Lexi-complete Online. Accessed 4/7/16. 46

47 Insulin glargine (Toujeo) Image: https://www.toujeo.com. Accessed 4/7/16. 2 2 47

48 Insulin glargine (Toujeo)  No change in physiological mechanism  Smaller amount of depot insulin  Smaller surface area  More gradual and prolonged release of hexamers  Smaller amount of liquid per unit  450 units (300 u/mL) vs. 300 units (100 u/mL) in Lantus pen Home PD. Am Diabetes Assoc 2014;2014:abstract 80-LB. 48

49 Head-to-Head: Toujeo vs. Lantus  Noninferiority met at 26 weeks (95% CI 0.1- 0.19)  Nocturnal hypoglycemia  31% lower in first 8 weeks (CI 0.53-0.91)  No difference at 26 weeks  Less weight gain (est. diff. 0.5 kg, p=0.037) Home PD. Am Diabetes Assoc 2014;2014:abstract 80-LB. 49

50 Basaglar (insulin glargine) Eli Lilly/Boerhinger Ingelheim. Introducing: Basaglar. https://www.basaglar.com/# (accessed 4/7/16).https://www.basaglar.com/# 3 3 50

51 Basaglar (insulin glargine)  Lilly/BI’s answer to Sanofi-Aventis’s Lantus  Same PK profile, not interchangeable  Approved for use in type 1 kids and adults, and type 2 adults  Available starting 12/2016 Blevins TC. Diabetes Obes Metab 2015;17:726-33. (ELEMENT 1) Eli Lilly/Boerhinger Ingelheim. Introducing: Basaglar. https://www.basaglar.com/# (accessed 4/7/16).https://www.basaglar.com/# 51

52 Head-to-Head: Basaglar vs. Lantus  Noninferiority met at 24 weeks  95% CI -0.002 to 0.219  Symptomatic and nocturnal hypoglycemia similar  Weight gain similar  0.36 kg Basaglar vs. 0.12 kg Lantus  Insulin antibodies similar Blevins TC. Diabetes Obes Metab 2015;17:726-33. (ELEMENT 1) 52

53 Humalog U-200 KwikPen Image: http://www.ulticare.com/pen-needles/. Accessed 4/11/16. 4 4 53

54 Humalog U-200 KwikPen  200 units/ml  600 units/pen (versus 300 units/pen)  Good for patients who go through 2 or more mealtime insulin pens each month Lexi-complete Online. Accessed 4/7/16. 54

55 Inhaled insulin (Afrezza) Images: Afrezza. https://www.afrezza.com/hcp 5 5 55

56 Inhaled insulin (Afrezza)  “Technosphere insulin”  Helps reduce injection barriers to therapy  Lungs have a large surface area and high bioavailability  New inhaler device called “Dreamboat”  Replace every 15 days  Insulin cartridges available:  4 units, 8 units, 12 units  Concerns: pulmonary toxicity/malignancy Lexi-complete Online. Accessed 4/7/16. Bode BW. Diabetes Care 2015;38:2266-73. Raskin P. Diabetes Obes Metab 2012;14:163-73. 56

57 Head-to-Head: Inhaled insulin vs. aspart  Mean change in HbA1c noninferior  More aspart patients achieved HbA1c <7.0% (30.7% vs. 18.3%)  Inhaled insulin had less hypoglycemia (9.8 vs 14.0 events/patient-month, p<0.0001)  Inhaled insulin patients experienced weight loss (-0.4 kg) vs. gain (+0.9 kg) for aspart patients (p=0.0102)  Most frequent AE = cough which led to discontinuation in 5.7% of patients Bode BW. Diabetes Care 2015;38:2266-73. 57

58 Dosing Chart Configurations Afrezza. https://www.afrezza.com/AfrezzaConfigurationChart.pdf 58

59 Diabetes Meds in the Pipeline  Novo Nordisk  Xultophy (insulin degludec + liraglutide)  Faster-acting insulin aspart  Semaglutide (oral and injectable)  Eli Lilly  BioChaperone insulin lispro R&D Pipeline. http://www.novonordisk.com/rnd/rd-pipeline.html. Accessed 4/11/16. Anderson G. Diabetes 2014;63(suppl 1). 59

60 60

61 Innovative Care Solutions and Ideas Patient Assistance Programs Coupons Medication Pricing Apps Medication Lists

62 Patient Assistance Programs (PAPs)  Provided by pharmaceutical companies  To provide brand-name medications  For low-income individuals who lack prescription drug coverage  Vs. coupon, sample, 340B, drug card, bulk replacement programs, and Medicare Part D  Advocate “PAPs are a long term solution to a current medication access problem” Am J Health-Syst Pharm. 2006; 63:1254-9. Sagall RJ. Pharmaceutical companies helping patients get their medications. Accessed at http://www.needymeds.org/indices/article.htm on 2/21/13. 62

63 Programs Available  NeedyMeds  http://www.needymeds.org http://www.needymeds.org  Partnership for Prescription Assistance  http://www.pparx.org http://www.pparx.org  RxAssist  http://www.rxassist.org http://www.rxassist.org  TogetherRx Access  http://www.togetherrxaccess.com http://www.togetherrxaccess.com  National Council on Patient Information and Education  http://www.talkaboutrx.org http://www.talkaboutrx.org  Manufacturers’ websites 63

64 Finding an application  Medications covered  Type (brand, generic)  Insurance status  Private insurance  Medicare Part D (coverage gap)  No insurance 64

65 Coupons  Discount the price of medications for a set number of fills  Search patient assistance websites for coupons  Hard copy cards at physician offices from drug company representatives 65

66 Medication Pricing - GoodRx  Losartan 50mg #30  Wal-Mart pricing by phone = $39.41 Price obtained by phone from Wal-Mart Neighborhood Market, 4404 S. Peoria Ave. Tulsa, OK on 4/11/16. 66

67 Medication Pricing - GoodRx Screenshots taken 4/7/16. 67

68 Medication Pricing - GoodRx Screenshots taken 4/7/16. 68

69 Medication Lists  MyMedSchedule.com 69

70 Medication Lists  My Medicine List  http://www.safemedication.com 70

71 Questions?

72 Diabetes Update 2016: New Drugs and New Methods of Care Kelly Murray, PharmD, BCACP Clinical Assistant Professor of Clinical Pharmacy OSU College of Osteopathic Medicine Emergency Department Clinical Pharmacist OSU Medical Center


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