1

Disclosure

0 I have no actual or potential conflict of interest in relation to this program or presentation.

0 I will not discuss off label or investigational use in my presentation.

Pharmacist Objectives

0 At the completion of this program, pharmacists will be able to:

0 Identify specific goals regarding diabetes management in the elderly population.

0 Discuss key concerns and risks in the elderly for certain medications used to treat diabetes.

0 Apply the principals covered from the 2017 ADA guidelines to patient cases.

2

Technician Objectives

0 At the completion of this program, technicians will be able to:

0 Identify specific goals regarding diabetes management in the elderly population.

0 Discuss key concerns and risks in the elderly for certain medications used to treat diabetes.

0 Identify key principals of the 2017 ADA guidelines.

Case 1

0 It’s Friday and you are reviewing this patient’s chart at 4:45pm: 70 y/o male in an adult family home.

0 On Lantus 20 units at bedtime

0 About 10 fasting blood glucose levels <70 in a month

0 What questions would you want to ask of the caregiver or patient?

0 Any concerns you have?

Case 1 Discussion Points

0 Has anything changed recently?

0 Other medications? Last A1C? Comorbidities? Goals?

0 When is the patient going low?

0 Is less than 70 concerning?

0 Did the patient experience symptoms while low and does that matter?

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Justification

0 Older persons have the highest prevalence of diabetes of any age group (22-33% in those aged ≥65 years).17

0 According to CDC projections in 2012, even if diabetes incidence levels off, the prevalence will double in the next 20 years, in part due to the aging of the population.5

0 Treatment can be complicated considering that often most of these patients are excluded from randomized controlled trials assessing treatments and treatment targets. This leaves us to extrapolate data from much younger populations which might not be appropriate for the older adult.

Justification cont.

0 One study examined the reasons for medication-related ED visits by older adults and found that insulin (13.9%) and oral hypoglycemic agents (10.7%) were two of the most common.8

Rates of diagnosed diabetes by age from 1980 to 2014 in the US.

https://www.cdc.gov/diabetes/statistics/prev/national/figbyage.htm

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Defining the “Elderly”

0 Approximations (not hard definitions):

0 Youngest Old: 65-74

0 Middle Old: 75-84

0 Oldest Old: 85-99

0 Centenarians: 100 and older

Diabetes goals in the Elderly

Reference 17

5

Shared Decision Making

0 Older patients tend to focus on functional status and independence.15

0 In a study comparing patient perceived burden on quality of life of treatments vs disease state complications, comprehensive diabetes treatments had similar results as those with intermediate complications.7

0 Important to ensure patients understand significance of risk factors and value of risk reduction in order to appropriately discuss treatments and targets.

Pharmacologic Concerns with Diabetes in the Elderly

Overall Treatment

0 Older patients may not benefit as much and may actually suffer from intensive glucose lowering12,14

0 Some benefit of intensive lowering not seen for 8-10 years.

0 Other co-morbidities may be more critical.

0 Goal is primarily to prevent hypoglycemia while providing reasonable control.0 This might mean tolerating some higher glucose levels.

0 Some data suggests that low glucose levels (<70) even without hypoglycemic symptoms may still have negative cardiac effects.13

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More Generalities

0 Usually unnecessary in the outpatient setting to establish control of diabetes therapy rapidly. It is ok to titrate to tolerance.

0 It may be prudent to start medications at a lower dose (even ½ or ¼) of the typical adult starting dose, if feasible.

0 “Start low, go slow, but still get somewhere.”

Hypoglycemia and Falls

0 Older patients may be:

0 More sensitive to the effects of hypoglycemia

0 Less able to recognize and appropriately manage symptoms of hypoglycemia

0 More likely to have end-stage complications (ie. peripheral neuropathy, retinopathy, etc) that contribute to a fall and affect recovery after a fall

Predictors

0 Strongest predictors of severe hypoglycemia have been found to be:18,21

0 Advanced age

0 Recent hospitalization

0 Polypharmacy

0 These are all fairly common among the elderly population.

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Renal/Hepatic Function

0 Decrease in function with advancing age.

0 Medications that the patient could tolerate at 50 might not be appropriate anymore now that they are 75.

0 Medications

that require renaldosage adj.:

0 Metformin

0 Sulfonylureas*

0 Repaglinide(Prandin)

0 DPP-4 inh.*

0 Canagliflozin(Invokana)

0 Medications that require hepaticdosage adj.:

0 Sulfonylureas

Functional Status

0 Is the patient correctly understanding instructions about medications and information about their disease state?

0 Hearing impairment3,4

0 Risk Factor: DM0 Due to peripheral neuropathy, CHD, low HDL, general poor health

0 Cognitive dysfunction10,22

0 Linked to both hyper- and hypoglycemia

0 Visual impairment

0 Does the patient have the manual dexterity to administer their medications?

End of Life20

0 Since comfort is the primary concern, agents that might cause nausea, GI disturbance, or excess weight loss (ie. metformin or GLP-1 agonists) may need to be discontinued.

0 Even insulin may need to be withdrawn in some patients.

0 Acceptable blood glucose goals can be as lenient as 200-300 mg/dL.

0 Patient and caregiver education about end-of-life goals important.

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Tips and Tricks

0 Metformin0 Low incidence of hypoglycemia as it does not increase

insulin release.

0 Could still cause hypoglycemia in combo with other agents (ie. sulfonylureas, insulin, etc.)

0 Renal considerations: Newer guidance…0 eGFR > 45 mL/minute/1.73 m2: no adjustment

0 eGFR 30-45 mL/minute/1.73 m2: Do not start. Already on? Consider risk vs benefit. (Some suggest ½ the dose and monitor every 3 months)

0 eGFR < 30 mL/minute/1.73 m2: Use is contraindicated.

Tips and Tricks11

0 Sulfonylureas

0 Glyburide is recommended to be avoided in the elderly considering its longer half-life in comparison to the other sulfonylureas.

0 More likely to cause hypoglycemia because less likely to match food intake.

0 Glipizide or glimepiride need to be used cautiously.

Tips and Tricks11

0 Meglitinides (Glinides): Repaglinide (Prandin) and Nateglinide (Starlix)

0 One advantage of these medications is flexible dosing for patients with irregular eating patterns.

0 Particularly useful in older patients who may not eat three meals per day.

0 Can potentially cause less hypoglycemia than SUs if administered and dosed appropriately.

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Tips and Tricks16

0 SGLT-2 Inhibitors: canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance)0 Patients ≥65 years old tend to experience a higher rate

of volume depletion than younger patients resulting dizziness and orthostasis.

0 Effects are dose-dependent and noticeable in those ≥75 years old.

0 Good starting doses:0 Invokana 100 mg daily

0 Farxiga 5 mg daily

0 Jardiance 10 mg daily

0 GLP-1 agonists

Product Needles Considerations Impact on A1c

Albiglutide(Tanzeum)

Comes with 29 gauge needle with pen.Patient must attach to pen.

Injection wait time (15-30 min after reconstitution)

0.6-1.0%

Dulaglutide(Trulicity)

Comes with needle already attached to pen

No reconstitutionneeded

0.9-1.4%

Exenatide (Byetta)

(Bydureon)

Byetta requires separate Rx for needles.Bydureon kit and pen do come with needles

Several steps for reconstitution with injection kit.Budureon pen should sit out 15 minutes before reconstituting.

0.8-1.5% BID

1.0-1.9% QWk

Liraglutide(Victoza)

Need Rx for needles No reconstitution needed

1.0-1.4%

Lixisenatide(Adlyxin)

Need Rx for needles No reconstitution needed

0.3-0.8%

Sliding Scale Insulin1

0 True SSI not recommended in the elderly according the “Beers List”.

0 Refers to sole use of short- or rapid-acting insulin to manage or avoid hyperglycemia in the absence of basal or long-acting insulin

0 Reason: Higher risk of hypoglycemia without improvement in hyperglycemia management regardless of care setting.

0 How to switch? Please see: Munshi MN, Florez H, et. al. Management of diabetes in long-term care and skilled nursing facilities. Diabetes Care 2016;39:308-18.

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Summary

0 Less intensive blood glucose goals should be considered in older patients with more co-morbidities.

0 Hypoglycemia, renal and hepatic function, and functional status are all important considerations when choosing appropriate therapy in the elderly person with diabetes.

0 Refer to specific slides for tips and tricks for managing elderly patients on common anti-hyperglycemic medications.

Case 2

0 72 y/o male has had a few falls recently including one that resulted in an ER visit where they measured a blood glucose of 42 mg/dL. You are asked to review his medication regimen and make adjustments, if necessary, to reduce his fall risk.

0 PMH: type 2 DM, peripheral neuropathy, and hyperlipidemia.0 Vitals today: BP: 132/74, P: 76, RR: 16, A1C 7.6%.0 Medications:

0 Glyburide 20 mg daily0 Metformin XR 2000 mg daily0 Gabapentin 600 mg TID0 Insulin glargine 10 units QHS0 Insulin lispro per sliding scale0 Rosuvastatin 20 mg daily

Case 2

0 Discuss with the people around you:

0 What questions would you like to ask?

0 What medications would you consider changing, if any?

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Case 2 Discussion Points

0 Kidney and liver function?

0 When are the lows? What preceded the recent 42?

0 Glyburide?

0 Sliding scale or Lantus?

0 Are the falls all associated with low BGs?

0 Gabapentin history?

0 Could they be mechanical in nature? (neuropathy)

0 Dehydration?

0 What is his A1C goal?

Reference 17

2017 ADA Guideline UpdatesFocusing on medication-related updates.

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Metformin2

0 New evidence suggests that long-term metformin use is associated with B-12 deficiency.

0 ACTION: Consider periodic measurement of B-12 levels and supplement as necessary.

0 FOCUS: Any patient, but especially those with anemia or peripheral neuropathy

“Biosimilar” Insulins9

0 Basaglar (Insulin glargine) 100 units/mL KwikPen

0 Approved through an abbreviated FDA approval pathway.

0 NOT interchangeable with Lantus (requires a new Rx).

0 Patients can be converted from Lantus on a unit-per-unit basis.

0 Potentially less expensive than Lantus, but still costly.

Agents with CVD benefits19,23

0 Sodium–Glucose Co-transporter 2 (SGLT2) Inhibitors

0 Currently ONLY data for empagliflozin (Jardiance)

0 NEW (12/16) indication: risk reduction of cardiovascular mortality in adults with type 2 diabetes mellitus and established cardiovascular disease

0 Based on the EMPA-REG OUTCOME trial.

0 Glucagon-like peptide 1 (GLP-1) receptor agonist

0 Currently ONLY data for liraglutide (Victoza)

0 Based on the LEADER trial.

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Acknowledgment of Cost9

2016

2017

New Algorithm9

0 Specifically for injectable therapy for patients with type II DM.

0 Reflects studies demonstrating non-inferiority of the following treatments:

0 Basal insulin + GLP-1 agonist

0 Basal insulin + Rapid-acting insulin (before largest meal)

0 BID dosing of premixed insulin

0 Also non-inferiority of:

0 Multiple dose premixed insulin

0 Basal-Bolus

2016

2017

http://professional.diabetes.org/sites/professional.diabetes.org/files/media/dc_40_s1_final.pdf

http://care.diabetesjournals.org/content/suppl/2015/12/21/39.Supplement_1.DC2/2016-Standards-of-Care.pdf

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2016

2017

2017

2016

New Cost Tables9

0 New tables were added due to concerns about the affordability of anti-hyperglycemic agents.

0 It is very important to consider insurance coverage status and also specific plan when developing a care plan for a patient with type II DM.

0 Most affordable medications (≤$160 Median AWP*):0 Metformin (except 1000mg

ER)0 Sulfonylureas0 Nateglinide (Starlix)0 Acarbose (Precose)

0 Most affordable insulins(≤$250 Median AWP*): 0 Human Regular U-100 and

U-500 vial and pen0 Human NPH U-100 vial0 NPH/Regular 70/30 U-100

vial

15

Summary

0 Consider monitoring for B-12 deficiency in your diabetic patients on Metformin.

0 Basaglar might be a cheaper option for some patients needing a basal insulin.

0 Victoza and Jardiance might be good options for your patients with co-morbid CVD.

0 NPH and Regular insulin might be cheaper options for some patients, but also have their limitations.

Case 3

0 A 65 y/o female with uncontrolled type 2 diabetes, hypertension, CKD stage 3 and depression.

0 Current A1c 9.2%, eGFR 43 mL/min, BP today 139/80

0 Medications:0 Humulin 70/30: 30 units BID

0 Metformin 1000 mg BID

0 Citalopram 20 mg daily

0 Lisinopril/HCTZ 20/12.5 mg daily

0 ASA-81mg daily

0 You are asked to recommend a plan to get this patient’s DM under control.

Case 3

0 What is this patient’s A1c goal?

0 What adjustments would you make to get this patient to goal based on the most recent guideline changes?

0 Any other concerns?

16

Reference 17

2016

2017

2017

2016

17

Case 3 Discussion Points

0 Renal function? (Metformin)

0 Compliance (Cost)? Diet?

0 Any lows?

0 Next step according to the guidelines for injectable therapy?

0 Would require switching to basal/bolus or other fixed analog insulin (ie. Humalog 70/30) to add TID dosing.

0 Oral therapy?

Conclusion

0 Recognition of importance and relevance of topic

0 Targets defined

0 Precautions to consider and minutia to keep in mind when it comes to selecting medications for the elderly patient with diabetes.

0 General guideline updates as related to medications summarized

Assessment Questions

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Assessment Question 1

0 According to the information presented, what is an appropriate A1C goal for an older patient with multiple co-morbidities and mild to moderate cognitive impairment?

a) < 7.5%

b) 7-8%

c) < 8%

d) 9-10%

Assessment Question 2

0 When a patient is initiated on metformin what should you consider monitoring for according to the ADA 2017 Guidelines?

a) B-12 deficiency

b) Elevated cobalamin levels

c) Elevated vitamin D levels

d) Increased constipation and shortness of breath

Assessment Question 3

0 What can be an issue with older patients taking GLP-1 inhibitors?

a) Complicated reconstitution steps

b) Lack of the dexterity to use the pens

c) Excess weight loss

d) All of the above

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Assessment Question 4

0 T or F: Some data suggests that low glucose levels (<70) even in the absence of hypoglycemic symptoms may still have negative cardiac effects.

Assessment Question 5

0 Which agents have positive clinical trial evidence and are now recommended in type 2 diabetic patients with co-morbid CVD disease for risk reduction of cardiovascular mortality?

a) Trulicity and Jardiance

b) Jardiance and Victoza

c) Prandin and Glucophage

d) Victoza and canagliflozin

Questions?

20

References

1. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc2015;63:2227-46.

2. Aroda VR, Edelstein SL, Goldberg RB, et al.; Diabetes Prevention Program Research Group. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab2016;101:1754–1761.

3. Bainbridge KE, Hoffman HJ, et al. Diabetes and hearing impairment in the United States: audiometric evidence from the National health and Nutrition Examination Survey, 1999 to 2004. Ann Intern Med 2008;149:1-10.

4. Bainbridge KE, Hoffman HJ, et al. Risk factors for hearing impairment among U.S. adults with diabetes: national Health and Nutrition Examination Survey, 1999 to 2004. Diabetes Care 2011;34:1540-45.

5. Boyle JP, Thompson TJ, et al. Projection of the year 2050 burden of diabetes in the US population in 1988-1994 and 2005-2006. Diabetes Care. 2009; 32:287-294.

References

6. Bremer JP, Jauch-Chara K, et. al. Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes. Diabetes Care 2009;32:1513-17.

7. Brown SE, Meltzer DO, et. al. Perceptions of quality-of-life effects of treatments for diabetes mellitus in vulnerable and nonvulnerable older patients. J Am Geriatr Soc. 2008;56:1183-90.

8. Budnitz DS, Lovegrove MC, et. al. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 2011;365:2002-9.

9. Cefalu WT, et al.; American Diabetes Association Standards of Medical Care in Diabetes 2017. Diabetes Care: The Journal of Clinical and Applied Research and Education 2017;40(supp. 1):S1-S135.

10. Cukierman T, Gerstein HC, et. al. Cognitive decline and dementia in diabetes: systematic overview of prospective observational studies. Diabetologia 2005;48:2460-69.

References

11. Gates BJ and Walker KM. Physiological changes in older adults and their effect on diabetes treatment. Diabetes Spectrum 2014;27:20-9.

12. Gerstein HC, Miller ME, et. al. Action to control cardiovascular risk in diabetes study group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-59.

13. Goto A, Arah OA, et. al. Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis. BMJ 2013;347:f4533.

14. Greenfield S, Billimek J, et. al. Comorbidity affects the relationship between glycemic control and cardiovascular outcomes in diabetes: a cohort study. Ann Intern Med 2009;151:854-60.

15. Huang ES, Gorawara-Bhat R, Chin MH. Self-reported goals of older patients with type 2 diabetes mellitus. J Am Geriatr Soc. 2005;53:306-11.

16. Janssen Pharmaceuticals: Invokana package insert. Titusville, N.J. Janssen Pharmaceuticals, 2013.

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References

17. Kirkman MS, Huang ES, et al. Consensus Report: Diabetes in Older Adults. Diabetes Care. 2012;35:2650-64.

18. Lipska KJ, Ross JS, et. al. National trends in US hospital admissions for hypoglycemia among Medicare beneficiaries, 1999-2011. JAMA Intern Med 2014;174:1116-24.

19. Marso SP, Daniels GH, Brown-Frandsen K, et al.; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311–322

20. Munshi MN, Florez H, et. al. Management of diabetes in long-term care and skilled nursing facilities. Diabetes Care 2016;39:308-18.

21. Shorr RI, Ray WA, et. al. Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med 1997;157:1681-86.

22. Whitmer RA, Karter AJ, et. al. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 2009;301:1565-72.

References

23. Zinman B, Wanner C, Lachin JM, et al.; EMPA-REG OUTCOME Investigators. Empagli- flozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117– 2128.