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. 2016 FIESTA ACCRA , GHANA HILLCREST HOSPITAL, TULSA, OKLAHOMA USA
MICHAEL OPONG-KUSI, MBA, DO,FAAFP
HILLCREST HOSPITAL,
TULSA, OKLAHOMA
USA

3. DIABETES IN GHANA
2016 FIESTA
Growing Obesity and sedentary life style especially in the cities.
Carbohydrate rich diet
Aging of the population in Ghana
Lack of primary medical care and screening

4. Overview Standards of Care 2016 Updates New Diabetes Therapies
2016 FIESTA
Standards of Care 2016 Updates
New Diabetes Therapies
Oral medications
Injectable medications
Insulin therapies
Innovative Care Solutions and Ideas

5. Objectives
2016 FIESTA
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.
Discuss availability and price of these new drugs in Ghana.

6. Standards of Care 2016 UpdatesMm

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

8. Testing All adults ≥45 years old regardless of weight
2016 FIESTA
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.

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

10. 2016 FIESTA

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

12. Where do diabetes meds work?
2016 FIESTA
Brain
Liver
↑ satiety
↓ glucose production
Pramlintide
Incretin mimetics
Insulin
Metformin
TZDs
Pramlintide
DPP-4 inh.
Incretin mimetics
Muscle and Adipose
↑ peripheral glucose uptake
Insulin
Metformin
TZDs
Pancreas
Intestines
↓ digestion and absorption of carbs
↑ insulin secretion
Insulin
Sulfonylureas
Meglitinides
DPP-4 inh.
Incretin mimetics
Metformin
a-glucosidase inh.
Kidneys
Delay gastric emptying
↓ glucose reabsorption
Pramlintide
Incretin mimetics
SGLT2 inhibitor

13. What level do they fix? FASTING MIXED POSTPRANDIAL Metformin SU
2016 FIESTA
FASTING
MIXED
POSTPRANDIAL
Metformin SU
Regular insulin
Rapid insulins
TZDs
Incretin mimetics
Meglitinides
Interm. insulin
Long insulin
a-glucosidase (-)
DPP-4 (-)
SGLT2 (-)
Incretin mimetics (Exen.)
Pramlintide

14. Incretin Effect Eat food  nutrients and glucose in the gut
2016 FIESTA
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:

15. Need for Drug Therapy That:
2016 FIESTA
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

16. Dipeptidyl Peptidase - 4 (DPP-4) Inhibitors
2016 FIESTA
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.

17. DPP-4 Inhibitors Mechanism:
2016 FIESTA
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:
Drucker DJ. Lancet 2006;368:

18. DPP-4 Inhibitors - Safety
2016 FIESTA
Adverse Effects:
Placebo-like: HA, URI, nasopharyngitis, UTI
Rare: pancreatitis, skin reactions, urticaria/angioedema
Contraindicated: Hx of pancreatitis, DKA, type 1 diabetes
Counseling:
With or without food
Lexi-complete Online. Accessed 4/7/16.

19. DPP-4 Inhibitors - Efficacy
2016 FIESTA
Average A1c reduction: %
Primarily acts on postprandial glucose
Remember they are glucose-dependent

20. DPP-4 Inhibitors Advantages: Disadvantages:
2016 FIESTA
Advantages:
No hypoglycemia as monotherapy
Weight neutral
Placebo-like Adverse effects
Beta cell preservation
Linagliptin – no renal adjustments needed
Disadvantages:
Modest A1c lowering
Cost
Long term safety unknown

21. DPP-4 Inhibitors Dosing Guide
2016 FIESTA
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
Lexi-complete Online. Accessed 4/7/16.

22. DPP-4 Inhibitors Dosing Guide
2016 FIESTA
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
Lexi-complete Online. Accessed 4/7/16.

23. GLP 1 Receptor Agonists (a.k.a. incretin mimetics)
2016 FIESTA
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.

24. GLP 1 Receptor Agonists (a.k.a. incretin mimetics)
2016 FIESTA
Mechanism: GLP1 analog
Increases incretin levels
Glucose-dependent increase in insulin secretion
Glucose-dependent inhibition of glucagon
Reduces gastric emptying
Increases satiety
Lexi-complete Online. Accessed 4/7/16.

25. GLP 1 Receptor Agonists (a.k.a. incretin mimetics)
2016 FIESTA
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
Shyangdan DS. Cochrane Database Syst Rev 2011.
Lexi-complete Online. Accessed 4/7/16.

26. GLP 1 Receptor Agonists (a.k.a. incretin mimetics)
2016 FIESTA
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:
Lexi-complete Online. Accessed 4/7/16.

27. GLP 1 Receptor Agonists (a.k.a. incretin mimetics)
2016 FIESTA
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.

28. Exenatide IR to ER Start weekly dose the day after D/C IR
2016 FIESTA
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
Lexi-complete Online. Accessed 4/7/16.

29. GLP 1 Receptor Agonists (a.k.a. incretin mimetics)
2016 FIESTA
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.

30. GLP 1 Receptor Agonists (a.k.a. incretin mimetics)
2016 FIESTA
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.

31. GLP-1 Agonists Dosing Guide
2016 FIESTA
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
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.

32. GLP-1 Agonists Dosing Guide
2016 FIESTA
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
Lyxumia (lixisenatide) – once daily prandial subq injection, dose TBA
Lexi-complete Online. Accessed 4/7/16.

33. Incretin Mimetic vs. DPP-4 Inhibitors
2016 FIESTA
Incretin Mimetic
DPP-4 Inhibitor
Delay gastric emptying
No effect on gastric emptying
Increase satiety
No increase in satiety
Lots of N/V
Placebo-like adverse rxn.
Weight loss
No change in weight
SC administration
PO administration
Drucker DJ. Lancet 2006;368:

34. SGLT2 Inhibitors Canagliflozin (Invokana) Dapagliflozin (Farxiga)
2016 FIESTA
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.

35. SGLT2 Inhibitors Mechanism of Action
2016 FIESTA
Blocks renal absorption of ~90% of excess glucose, promotes urinary glucose excretion.
Highly selective inhibitor of sodium glucose cotransporter 2
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.

36. SGLT2 Inhibitors Adverse Effects: Contraindications:
2016 FIESTA
Adverse Effects:
Urinary/genital infections
Hypotension
Bone fractures
DKA
Hyperkalemia
Renal insufficiency
Contraindications:
Hypersensitivity
ESRD/Dialysis
Lexi-complete Online. Accessed 4/7/16.

37. SGLT2 Inhibitors Counseling Points: Efficacy With or without food
2016 FIESTA
Counseling Points:
With or without food
Before the first meal of the day
Efficacy
% A1c lowering
Mostly post-prandial glucose lowering
Lexi-complete Online. Accessed 4/7/16.

38. SGLT2 Inhibitors Advantages: Disadvantages:
2016 FIESTA
Advantages:
New mechanism, another option
Less hypoglycemia
Weight loss
Potential BP-lowering
Disadvantages:
DKA
Price / insurance coverage
May encourage diet indiscretions?
Cancer risk?

39. Dosing Recommendations
2016 FIESTA
Canagliflozin (Invokana)
100mg po once daily before first meal of the day
eGFR = 100mg po daily max
eGFR <45 = use is not recommended/Contraindicated
Dapagliflozin (Forxiga)
10 mg po once daily without regard to meals
eGFR <60 = use is not recommended/Contraindicated
Empagliflozin (Jardiance)
10mg po once daily without regard to meals
Lexi-complete Online. Accessed 4/7/16.

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

41. New Insulin Therapies

42. New Insulin Therapies Ideal basal insulin Bolus insulin Peakless
2016 FIESTA
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.

43. Insulin degludec (Tresiba)1
Insulin degludec (Tresiba)
2016 FIESTA
Image: Accessed 4/11/16.

44. Insulin degludec (Tresiba)
2016 FIESTA
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.

45. Insulin degludec Mechanism
2016 FIESTA
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:

46. Head-to-Head: Insulin degludec vs.
2016 FIESTA
Insulin glargine
Noninferiority criteria met (95% CI 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 to 0.05)
Nocturnal hypoglycemia 34% lower (p=0.0049)
Weight gain higher with degludec (est. diff kg; p<0.0001)
Heller S. Lancet 2012;379: (BEGIN)
Mathieu C. J Clin Endocrinol Metab 2013;98: (BEGIN:Flex T1)

47. HbA1c Comparison 2016 FIESTA
Mathieu C. J Clin Endocrinol Metab 2013;98: (BEGIN:Flex T1)

48. Insulin degludec (Tresiba)
2016 FIESTA
100 units/mL and 200 units/mL available
No conversion calculation necessary; same unit per unit dose
Dosing:
Type 1: 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: (BEGIN:Flex T1)
Lexi-complete Online. Accessed 4/7/16.

49. Insulin glargine (Toujeo)2
Insulin glargine (Toujeo)
2016 FIESTA
Image: Accessed 4/7/16.

50. Insulin glargine (Toujeo)
2016 FIESTA
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.

51. Head-to-Head: Toujeo vs. Lantus
2016 FIESTA
Noninferiority met at 26 weeks (95% CI )
Nocturnal hypoglycemia
31% lower in first 8 weeks (CI )
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.

52. Basaglar (insulin glargine)3
Basaglar (insulin glargine)
2016 FIESTA
Eli Lilly/Boerhinger Ingelheim. Introducing: Basaglar. (accessed 4/7/16).

53. Basaglar (insulin glargine)
2016 FIESTA
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: (ELEMENT 1)
Eli Lilly/Boerhinger Ingelheim. Introducing: Basaglar. (accessed 4/7/16).

54. Head-to-Head: Basaglar vs. Lantus
2016 FIESTA
Noninferiority met at 24 weeks
95% CI to 0.219
Symptomatic and nocturnal hypoglycemia similar
Weight gain similar
0.36 kg Basaglar vs kg Lantus
Insulin antibodies similar
Blevins TC. Diabetes Obes Metab 2015;17: (ELEMENT 1)

55. 4 Humalog U-200 KwikPen 2016 FIESTA
Image: Accessed 4/11/16.

56. Humalog U-200 KwikPen 200 units/ml
2016 FIESTA
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.

57. Inhaled insulin (Afrezza)5
Inhaled insulin (Afrezza)
2016 FIESTA
Images: Afrezza.

58. Inhaled insulin (Afrezza)
2016 FIESTA
“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:
Raskin P. Diabetes Obes Metab 2012;14:

59. Head-to-Head: Inhaled insulin vs. aspart
2016 FIESTA
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:

60. Dosing Chart Configurations
2016 FIESTA
Afrezza.

61. Diabetes Meds in the Pipeline
2016 FIESTA
Novo Nordisk
Xultophy (insulin degludec + liraglutide)
Faster-acting insulin aspart
Semaglutide (oral and injectable)
Eli Lilly
BioChaperone insulin lispro
R&D Pipeline. Accessed 4/11/16.
Anderson G. Diabetes 2014;63(suppl 1).

62. FIESTA 2016 : ACCRA GHANA
2016 FIESTA
THANK YOU??
MEDA MO ASE PII

63. 2016 FIESTA

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

65. Patient Assistance Programs (PAPs)
2016 FIESTA
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:
Sagall RJ. Pharmaceutical companies helping patients get their medications. Accessed at on 2/21/13.

66. Programs Available NeedyMeds Partnership for Prescription Assistance
2016 FIESTA
NeedyMeds
Partnership for Prescription Assistance
RxAssist
TogetherRx Access
National Council on Patient Information and Education
Manufacturers’ websites

67. Finding an application
2016 FIESTA
Medications covered
Type (brand, generic)
Insurance status
Private insurance
Medicare Part D (coverage gap)
No insurance

68. Coupons Discount the price of medications for a set number of fills
2016 FIESTA
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

69. Medication Pricing - GoodRx
2016 FIESTA
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.

70. Medication Pricing - GoodRx
2016 FIESTA
Screenshots taken 4/7/16.

71. Medication Pricing - GoodRx
2016 FIESTA
Screenshots taken 4/7/16.

72. Medication Lists
2016 FIESTA
MyMedSchedule.com

73. Medication Lists My Medicine List http://www.safemedication.com
2016 FIESTA
My Medicine List

74. Questions?

75. 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